Safety and immunogenicity of bovine rotavirus vaccine RIT 4237 in 3-month-old infants. Prolonged efficacy of rhesus rotavirus vaccine in Swedish children. Evaluation of rhesus rotavirus vaccine (MMU 18006) in infants and young children. Efficacy of live, attenuated, human rotavirus vaccine 89-12 in infants: a randomised placebo-controlled trial. Protective effect of WC3 vaccine against rotavirus diarrhea in infants during a predominantly serotype 1 rotavirus season. Reactions to and antigenicity of two human-rhesus rotavirus reassortant vaccine candidates of serotypes 1 and 2 in Venezuelan infants. Safety, immunogenicity, and protective efficacy of one and three doses of the tetravalent rhesus rotavirus vaccine in infants in Lima, Peru. Rhesus Rotavirus candidate vaccine. Clinical trial in children vaccinated between 2 and 5 months of age. Trial of an attenuated bovine rotavirus vaccine (RIT 4237) in Gambian infants. Evaluation of the antigenicity and reactogenicity of varying formulations of the rhesus rotavirus-based quadrivalent and the M37 rotavirus vaccine candidates. Efficacy of the rhesus rotavirus-based quadrivalent vaccine in infants and young children in Venezuela. Comparison of immunogenicity and efficacy of rhesus rotavirus reassortant vaccines in breastfed and nonbreastfed children. US Rotavirus Vaccine Efficacy Group. A field study of the safety and efficacy of two candidate rotavirus vaccines in a Native American population. Safety and efficacy of high-dose rhesus-human reassortant rotavirus vaccines--report of the National Multicenter Trial. United States Rotavirus Vaccine Efficacy Group. Randomised placebo-controlled trial of rhesus-human reassortant rotavirus vaccine for prevention of severe rotavirus gastroenteritis. Evaluation of the efficacy of a low-passage bovine rotavirus (strain WC3) vaccine in children in Central Africa. Field trial of rhesus rotavirus or human-rhesus rotavirus reassortant vaccine of VP7 serotype 3 or 1 specificity in infants. The Elmwood, Panorama, and Westfall Pediatric Groups. Immunogenicity of tetravalent rhesus rotavirus vaccine administered with buffer and oral polio vaccine. Simultaneous administration of rhesus rotavirus vaccine and oral poliovirus vaccine: immunogenicity and reactogenicity. Early phase II trial of human rotavirus vaccine candidate RV3. Field trial of rhesus rotavirus vaccine in infants. Candidate rotavirus vaccine (rhesus rotavirus strain) in children: an evaluation. An efficacy trial of the rhesus rotavirus vaccine in Maryland. The Clinical Study Group. Efficacy of two doses of RIT 4237 bovine rotavirus vaccine for prevention of rotavirus diarrhoea. Immunogenicity and safety of rhesus-human rotavirus reassortant vaccines with serotype 1 or 2 VP7 specificity. Evaluation of the M37 human rotavirus vaccine in 2- to 6-month-old infants. Evaluation of WC3 rotavirus vaccine and correlates of protection in healthy infants. Evaluation of the protective efficacy of a serotype 1 bovine-human rotavirus reassortant vaccine in infants. Neonatal rotavirus vaccination with RIT 4237 bovine rotavirus vaccine: a preliminary report. Evaluation of RIT 4237 bovine rotavirus vaccine in newborn infants: correlation of vaccine efficacy to season of birth in relation to rotavirus epidemic period. Safety and immunogenicity of live, attenuated human rotavirus vaccine 89-12. Immune protection of infants against rotavirus gastroenteritis by a serotype 1 reassortant of bovine rotavirus WC3. Comparison of reactogenicity and antigenicity of M37 rotavirus vaccine and rhesus-rotavirus-based quadrivalent vaccine. Clinical evaluation of a single oral dose of human-bovine (UK) reassortant rotavirus vaccines Wa x UK (P1A[8],G6) and Wa x (DS-1 x UK) (P1A[8],G2). Reactogenicity and immunogenicity of a high-titer rhesus rotavirus-based quadrivalent rotavirus vaccine. Immunogenicity, safety and protective efficacy of one dose of the rhesus rotavirus vaccine and serotype 1 and 2 human-rhesus rotavirus reassortants in children from Lima, Peru. Live attenuated oral rotavirus vaccine. Safety and immunogenicity of tetravalent rhesus-based rotavirus vaccine in Bangladesh. Immunogenicity, safety and efficacy of tetravalent rhesus-human, reassortant rotavirus vaccine in Belém, Brazil. Protection of infants against rotavirus diarrhoea by RIT 4237 attenuated bovine rotavirus strain vaccine. Comparative evaluation of reactogenicity and immunogenicity of two dosages of oral tetravalent rhesus rotavirus vaccine. US Rhesus Rotavirus Vaccine Study Group. Evaluation of a bovine-human rotavirus reassortant vaccine in infants. Immunogenicity and reactogenicity of lowered doses of rhesus rotavirus vaccine strain MMU 18006 in young children. [Oral vaccination with live attenuated rotavirus]. Clinical studies of a quadrivalent rotavirus vaccine in Venezuelan infants. Prospective study of diarrheal diseases in Venezuelan children to evaluate the efficacy of rhesus rotavirus vaccine. A comparative evaluation of the safety and immunogenicity of a single dose of unbuffered oral rhesus rotavirus serotype 3, rhesus/human reassortant serotypes 1, 2 and 4 and combined (tetravalent) vaccines in healthy infants. Effect of dose and a comparison of measures of vaccine take for oral rhesus rotavirus vaccine. The Maryland Clinical Studies Group. Reactogenicity and antigenicity of rhesus rotavirus vaccine (MMU-18006) in newborn infants in Venezuela. Failure of live, attenuated oral rotavirus vaccine. Evaluation of rhesus rotavirus monovalent and tetravalent reassortant vaccines in US children. US Rotavirus Vaccine Efficacy Group. Protection of Peruvian children against rotavirus diarrhea of specific serotypes by one, two, or three doses of the RIT 4237 attenuated bovine rotavirus vaccine. Phase 1 trial of a candidate rotavirus vaccine (RV3) derived from a human neonate. Protective efficacy against serotype 1 rotavirus diarrhea by live oral rhesus-human reassortant rotavirus vaccines with human rotavirus VP7 serotype 1 or 2 specificity. Safety and immunogenicity of live attenuated human-bovine (UK) reassortant rotavirus vaccines with VP7-specificity for serotypes 1, 2, 3 or 4 in adults, children and infants. A trial of RIT-4237 rotavirus vaccine in 1-month-old infants. Efficacy and safety of high-dose rhesus-human reassortant rotavirus vaccine in Native American populations. A comparative trial of rhesus monkey (RRV-1) and bovine (RIT 4237) oral rotavirus vaccines in young children. Clinical efficacy of the RIT 4237 live attenuated bovine rotavirus vaccine in infants vaccinated before a rotavirus epidemic. Concurrent administration of rhesus rotavirus tetravalent (RRV-TV) vaccine with pentavalent diphtheria-pertussis-tetanus-Haemophilus influenzae beta-inactivated polio and hepatitis B vaccines.
To assess the safety and immunogenicity of bovine rotavirus vaccine, we administered attenuated strain RIT 4237 to 54 inner-city infants randomized to one of three groups in a double-blind fashion to receive a dose at 3 and 5 months of age of either placebo, vaccine virus at 10(7) TCID50/ml, or vaccine virus at 10(8) TCID50/ml. Vaccination began in early fall 1984, and continued through spring 1985. Forty-nine infants received one dose of vaccine or placebo; 43 received both doses of vaccine or placebo. At 2 and 3 months after vaccination, homologous geometric mean neutralizing antibody titers were significantly higher in children who received either dose of vaccine compared with placebo recipients. Cumulative seroconversion to bovine rotavirus after either dose of vaccine virus was 87% at 6 months of age. Seroconversion was significantly higher (P less than 0.01) in both vaccine groups compared with the placebo group. No ill effects were associated with vaccine administration. RIT 4237 vaccine appears to be safe and immunogenic when administered to young infants living in the United States. nan Orally administered rhesus rotavirus vaccine was evaluated in a placebo-controlled study in young children and infants (ages, eight months to 61 months). Thirteen children received the rotavirus vaccine, and ten children served as the control group. The vaccine was well tolerated. There were no significant differences between the vaccine recipients and the control group in the number of child-days with temperatures greater than or equal to 37.8 C, vomiting, diarrhea, or cough. There were significantly more child-days of rhinorrhea among the vaccine recipients than there were among the control group. The vaccine recipients under two years of age passed a larger number of stools than did the children in the control group, and vaccine recipients had significantly more semiformed and unformed stools than did the children receiving the placebo. All twelve of the children tested were positive for viral shedding. Peak viral shedding occurred on days three and five postvaccination. On day eight, over one-half of the children from whom a stool specimen was obtained were still shedding rotavirus. Children less than two years old shed more rotavirus in their stool than did children more than two years old. All 13 vaccine recipients had a fourfold or greater rise in titer of antibody as measured by plaque reduction, tube neutralization, complement fixation, and/or immune adherence hemagglutination. Rotavirus is the most common cause of severe, dehydrating diarrhoea in infants worldwide. We assessed the safety, immunogenicity, and efficacy of a live, oral human rotavirus vaccine, 89-12, in US children in a randomised, placebo-controlled, double-blind multicentre trial.
                215 healthy infants were enrolled, of whom 213 were given two doses of 89-12 (containing 1x10(5) plaque-forming units) or placebo, and 213 were followed up through one rotavirus season. The frequency of side-effects was compared for 7 days after each dose of vaccine. Immune responses to rotavirus were assessed by serum and stool IgA, and by serum 89-12 neutralising titres. The primary outcome variable (protection from rotavirus disease) was evaluated by comparing the frequencies of rotavirus gastroenteritis in an intention-to-treat analysis.
                Adverse reactions were mild. Low-grade fever (> or = 38.1 degrees C) after the first dose was the only side-effect significantly more common in the vaccine group than in the placebo group (21 [19%] vs 5 [5%], p=0.001). An immune response to vaccine was detected in 94.4% of vaccinees. Rotavirus disease occurred in 18 of 107 placebo recipients and two of 108 vaccine recipients (vaccine efficacy 89.0% [95% CI 65.4-94.5]). Ten infants in the placebo group but none in the vaccine group were presented for medical care.
                The 89-12 rotavirus vaccine was safe and immunogenic and provided a high degree of protection against rotavirus disease. Further investigations of this vaccine are needed to confirm these findings in other settings. We used a double-blind, placebo-controlled trial to study the efficacy of WC3 rotavirus vaccine administered to 104 infants (ages, three to 12 months) before the rotavirus season. Forty-nine infants received vaccine; 55 received placebo. Rotavirus disease during this season was predominantly caused by a serotype 1 strain. In placebo recipients there were 14 cases of rotavirus diarrhea (attack rate, 25%); 11 were moderate to severe (attack rate, 20%). Vaccinees experienced only three cases of rotavirus disease (attack rate, 6.1%), all mild. When all cases (whether associated with rotavirus or not) of clinically significant diarrhea (CSD) were evaluated, WC3 vaccine provided statistically significant (P less than .01) protection against the total number of episodes of CSD and reduced the number of days of CSD-associated diarrhea, vomiting, fever, or illness. Seventy-one percent of the WC3-vaccinated infants had serum antibody responses to the vaccine. The 14 placebo recipients who experienced natural disease predominantly had antibody responses to serotype 1. Sera taken after the rotavirus season revealed a nearly identical rate (40%) of natural rotavirus infection in the vaccinated and placebo groups. The reactions to and antigenicity of two human-rhesus rotavirus (RRV) reassortants (human rotavirus strain D x RRV and human rotavirus strain DS1 x RRV) with the VP7 neutralization specificity of a serotype 1 or serotype 2 rotavirus were evaluated in a placebo-controlled double-blind trial in 116 1- to 5-month-old infants in Caracas, Venezuela. The children were randomly divided into five groups to receive orally the following inocula: (i) 10(4) PFU of D x RRV reassortant; (ii) 10(4) PFU of DS1 x RRV reassortant; (iii) 10(4) PFU of RRV; (iv) 5 x 10(3) PFU of D x RRV and 5 x 10(3) PFU of RRV; and (v) placebo. The children were examined daily for 7 days following vaccine administration; 8 to 26% of the vaccinated infants developed a mild febrile reaction which in most cases lasted only 1 day. Seroresponses to rotavirus were observed in 39 to 65% of the vaccinees by plaque neutralization assay and in 57 to 88% by an immunoglobulin A enzyme-linked immunosorbent assay. Vaccine shedding was detected in 53 to 86% of the vaccinees. Analysis of neutralization antibody responses indicates that the VP4 protein represents an important component of the response induced by the vaccines. An oral rhesus-human rotavirus tetravalent (RRV-TV) vaccine (10(4) pfu of rhesus rotavirus [type G3] and of 3 human-rhesus reassortants [G1, G2, and G4]) was evaluated in a field trial in Lima, Peru. At 2, 3, and 4 months of age, infants received either a dose of RRV-TV, an initial dose of vaccine followed by a dose of placebo at 3 and 4 months, or a dose of placebo. Rotavirus-specific IgA responses were detected by ELISA in 75% of the three-dose vaccine group, 59% of the one-dose vaccine group (P = .05), and 24% of the placebo group (P < .001): 64%, 48%, and 12% of each group, respectively, had a neutralizing antibody response to at least 1 serotype. Both one and three doses of vaccine failed to induce a significant level of protection against rotavirus diarrhea; however, they did provide some protection (range, 35%-66%) against more severe rotavirus diarrhea, especially for episodes caused by type G1. Live attenuated oral rhesus Rotavirus candidate vaccine (strain MMU 18006 [lot RRV-1]) was evaluated for immunogenicity, safety, and clinical protection in a double-blind, placebo-controlled trial involving 200 infants aged 2 to 5 months when vaccinated. Vaccine-induced fourfold or greater rise of Rotavirus antibodies was seen in 62% of the infants. Febrile reactions of short duration on days 3 and/or 4 after vaccination occurred in 26% of the vaccine recipients. The clinical follow-up covered two Rotavirus seasons, in which serotypes 1 and 4 were prevalent. There were 16 cases of confirmed Rotavirus diarrhea in the placebo-treated group and 10 in the vaccine-treated group; from this a vaccine protection rate of 38% was derived. Clinical severity of Rotavirus diarrhea was assessed by a score; 13 cases in the placebo-treated group and 5 in the vaccine-treated group were regarded as severe or moderately severe, giving a vaccine protection rate of 67%. The rhesus Rotavirus vaccine induces partial protection against heterotypic Rotavirus disease, but the level of protection achieved with the present vaccine dose in this age group appears to be insufficient for a general Rotavirus vaccination. A randomised, controlled trial of bovine rotavirus vaccine was undertaken in Gambian infants. Three doses were administered, from the age of ten weeks, concurrently with oral or killed polio vaccine. Prevaccination rotavirus neutralising antibody levels were high. 84/185 infants (45%) showed an increase in neutralising antibody titre after receiving rotavirus vaccine, compared with 20/91 (22%) unvaccinated infants. Clinical rotavirus infection was detected in 24/78 (31%) children in the rotavirus/oral polio group, 34/83 (41%) children in the placebo/oral polio group, and 23/92 (25%) children in the rotavirus/killed polio group, giving an overall vaccine efficacy of 33% (95% CI 4-53%). RIT 4237 did not appear to reduce the severity of clinical infections. Most cases (92%) were caused by rotaviruses with short RNA electropherotypes. Serological responses to rotavirus vaccination appeared unaffected by the concurrent administration of oral polio vaccine. Lower types 1 and 3 polio antibody levels were found in children who received oral polio and rotavirus vaccines but the differences were not statistically significant. Three phase I trials of the rhesus rotavirus (RRV)-based quadrivalent vaccine [composed of serotype 3 (RRV), and serotypes 1 (D x RRV), 2 (DS1 x RRV), and 4 (ST3 x RRV) human rotavirus x RRV reassortants] and the M37 (nursery strain) rotavirus vaccine candidates were conducted in an attempt to find a safe and optimally antigenic formulation. Infants 10-20 weeks old received, in trial I, 1) the quadrivalent vaccine as two separate bivalent doses (1 x 10(4) PFU each of D x RRV and RRV, followed 4 weeks later by 1 x 10(4) PFU each of DS1 x RRV and ST3 x RRV) or 2) placebo; in trial II, 1) one dose of quadrivalent vaccine (10(4) PFU of each component), or 2) two doses of quadrivalent vaccine, or 3) a 10(4) PFU dose of M37 vaccine, or 4) M37 vaccine followed by the quadrivalent vaccine, or 5) placebo; in trial III, 1) a dose of a higher-titered quadrivalent vaccine (10(5) PFU of each component), or 2) two doses of higher titered quadrivalent vaccine, or 3) a dose of higher titered M37 vaccine (10(5) PFU) or 4) two doses of M37 vaccine (10(5) PFU), or 5) M37 vaccine (10(5) PFU) followed by the higher titered quadrivalent vaccine, or 6) placebo. A mild, transient fever during the first week postvaccination was associated with the bivalent or quadrivalent vaccines but not with the M37 vaccine. Fourfold or greater serum IgA ELISA responses to rotavirus were observed in 48-92% of the infants receiving quadrivalent vaccine and in 32-50% of those receiving M37 vaccine.(ABSTRACT TRUNCATED AT 250 WORDS) Rotaviruses are the principal known etiologic agents of severe diarrhea among infants and young children worldwide. Although a rhesus rotavirus-based quadrivalent vaccine is highly effective in preventing severe diarrhea in developed countries, in developing countries its efficacy has been less impressive. We thus conducted a catchment study in Venezuela to assess the efficacy of the vaccine against dehydrating diarrhea.
                In this randomized, double-blind, placebo-controlled trial, 2207 infants received three oral doses of the quadrivalent rotavirus vaccine (4x10(5) plaque-forming units per dose) or placebo at about two, three, and four months of age. During approximately 19 to 20 months of passive surveillance, episodes of gastroenteritis were evaluated at the hospital.
                The vaccine was safe, although 15 percent of the vaccinated infants had febrile episodes (rectal temperature, > or =38.1 degrees C) during the six days after the first dose, as compared with 7 percent of the controls (P<0.001). However, the vaccine gave 88 percent protection against severe diarrhea caused by rotavirus and 75 percent protection against dehydration, and produced a 70 percent reduction in hospital admissions. Overall, the efficacy of the vaccine against a first episode of rotavirus diarrhea was 48 percent. Horizontal transmission of vaccine virus was demonstrated in 15 percent of the vaccine recipients and 13 percent of the placebo recipients with rotavirus-positive diarrhea.
                In this study in a developing country, the quadrivalent rhesus rotavirus-based vaccine induced a high level of protection against severe diarrheal illness caused by rotavirus. To evaluate whether breastfeeding affected the immunogenicity and/or efficacy of candidate rhesus-human rotavirus reassortant vaccines.
                A total of 989 healthy infants between 4 and 26 weeks of age were enrolled into a 23-center, prospective, randomized, double-masked, controlled study of the safety, immunogenicity, and efficacy of three doses (4 x 10(4) plaque-forming units) of monovalent rhesus-human viral protein 7, or G, serotype 1 reassortant vaccine, (RRV-S1) or tetravalent vaccine (RRV-TV) consisting of rhesus-human reassortant G serotypes 1, 2, and 4, and the parent RRV G serotype 3. Vaccine efficacy was compared in the breastfed and nonbreastfed children as well as seroconversion rates and postvaccination geometric mean titers (GMTs) of neutralizing antibodies to human serotypes 1, 2, 3, and 4, RRV, and immunoglobulin A to RRV. GMTs in the two feeding groups were compared with and without adjustment for age at initiation of vaccination, prevaccination antibody titers, and the age and prevaccination titer interaction.
                The seroconversion rates to both vaccines by one or more assays were similar for the breastfed and the nonbreastfed groups (RRV-S1, 84% and 85%, respectively; RRV-TV, 94% and 93%, respectively). There were no significant differences in postvaccination GMTs to either vaccine, measured by any serologic assay, in the two feeding groups. The efficacy of the RRV-S1 vaccine was not significantly lower among the breastfed children than the nonbreastfed children (28% and 39%, respectively). RRV-TV, which is the vaccine being further evaluated for licensure, was equally protective in breastfed and nonbreastfed infants (50% and 51%, respectively). Logistic regression analysis, taking into account differences in age at vaccination and day 1 titer, revealed no evidence of differential vaccine efficacy in the two feeding groups for either vaccine.
                These results indicate that the RRV-TV vaccine, given as three doses of 4 x 10(4) plaque-forming units, induces similar seroresponses and protection in breastfed and nonbreastfed US children. A double-blind, randomized, placebo-controlled trial was conducted to evaluate the safety and efficacy of a rhesus rotavirus vaccine and RIT 4237, a bovine rotavirus vaccine, in a Navajo population. Infants aged 2-5 months were randomized to receive one dose of either 10(4) pfu of the rhesus rotavirus vaccine or 10(8) pfu of the RIT 4237 vaccine or placebo. Eleven (10.2%) of 108 infants in the rhesus vaccine group, 11 (10.4%) of 106 in the RIT 4237 group, and 9 (8.4%) of 107 in the placebo group experienced rotavirus diarrhea during the follow-up period of 17 months. Thus, in this population, neither vaccine was efficacious in preventing rotavirus diarrhea. Rotavirus is a leading cause of morbidity and mortality from dehydrating gastroenteritis in infants and young children worldwide. Virtually every child is infected by age 4 years, justifying universal childhood immunization when a safe and effective vaccine is available. We report the results of a multicenter, placebo-controlled field trial in the United States of monovalent serotype 1 and tetravalent (TV) rhesus-human reassortant rotavirus vaccines (RRVs).
                In this randomized, double-blind trial, 1278 healthy infants ages 5 to 25 weeks received three oral doses of RRV serotype 1, RRV-TV, or a placebo at approximately 2, 4, and 6 months of age. Vaccines contained 4 x 10(5) plaque-forming units of virus. Gastroenteritis episodes were monitored, and severity was graded throughout one rotavirus season. Two stool specimens per episode were tested for rotavirus.
                The incidence of reactions did not differ among treatment groups during the 5-day, postvaccination safety surveillance period for any of the three doses. Both vaccines significantly reduced the incidence of rotavirus gastroenteritis. Vaccination was most protective against serious rotavirus illness; RRV-TV prevented 49% of rotavirus episodes, 80% of very severe episodes, and 100% of dehydrating rotavirus illness. Reduction of rotavirus disease by RRV-TV resulted in significantly fewer total episodes of gastroenteritis of all causes and an 82% reduction in all cases of dehydrating diarrhea.
                RRV-TV is highly protective against very severe, dehydrating rotavirus gastroenteritis. Rotavirus is the most common cause of acute childhood gastroenteritis. Vaccination with live oral heterologous rotavirus vaccines may prevent rotavirus gastroenteritis. We assessed the efficacy of rhesus-human reassortant rotavirus tetravalent vaccine (RRV-TV) against severe rotavirus gastroenteritis in Finnish children in a randomised placebo-controlled double-blind trial.
                Placebo or RRV-TV (titre 4x10(5) plaque-forming units) was given to infants at ages 2, 3, and 5 months. The children were followed up for one or two rotavirus epidemic seasons. The main outcome measure was protection against severe rotavirus gastroenteritis (score > or =11 on a 20-point severity scale). 2398 children were enrolled and received at least one dose of RRV-TV (n=1191) or placebo (n=1207). The primary efficacy analysis was based on children who received three doses of RRV-TV (n=1128) or placebo (n=1145).
                256 episodes of rotavirus gastroenteritis occurred at any time during the study; 65 were among 1191 RRV-TV recipients, and 191 among 1207 placebo recipients (vaccine efficacy 66% [95% CI 55-74]; intention-to-treat analysis). 226 episodes were included in the primary efficacy analysis of fully vaccinated children (54 among 1128 RRV-TV recipients, 172 among 1145 placebo recipients; vaccine efficacy 68% [57-76]). 100 episodes were severe, eight in RRV-TV recipients and 92 in placebo recipients (vaccine efficacy 91% [82-96]).
                RRV-TV vaccine was highly effective against severe rotavirus gastroenteritis in young children. Incorporation of this vaccine into routine immunisation schedules of infants could reduce severe rotavirus gastroenteritis by 90% and severe gastroenteritis of all causes in young children by 60%. The safety and efficacy of a WC3 rotavirus vaccine was evaluated in a double-blind placebo-controlled trial involving 472 children in Bangui (Central African Republic). Each child received two doses of either placebo (235 children) or vaccine (237 children) at a 1-month interval, the first dose being given at 3 months of age. During the follow-up survey 9 months after the first dose, 117 rotavirus diarrhoeas were observed, 59 in the placebo group, 58 in the vaccinated group. The only positive effect of the vaccine was a significantly higher proportion of mild rotavirus diarrhoeal episodes in the vaccinated group than in the placebo group. Of the children in the vaccinated group, 60% had a positive immune response to WC3 rotavirus when tested by plaque reduction seroneutralization. Orally administered live rhesus monkey rotavirus vaccine (RRV, VP7 serotype 3) and human-rhesus reassortant rotavirus vaccine (DxRRV, VP7 serotype 1) were evaluated in a placebo-controlled field trial of 223 infants 2-4 months old. Both vaccines were mildly reactogenic but were generally well tolerated in the 10 days after vaccination. RRV and DxRRV were immunogenic, inducing serum antibody responses in 78% and 71% of the vaccines, respectively. Efficacy of RRV vaccine was 66% (P = .01) and of DxRRV vaccine 77% (P = .002) against rotavirus-associated illness in the first season after vaccination. Efficacy of RRV vaccine against rotavirus-associated illness over three rotavirus seasons was 51.2% (P = .045) and of DxRRV vaccine was 67.3% (P = .006). RRV vaccine provided heterotypic protection of 58.5% (P = .041) and DxRRV vaccine provided homotypic protection of 72.8% (P = .005) over three seasons against the predominant serotype 1 rotavirus. Between January and November 1989, we studied 174 infants aged 6 to 16 weeks in a randomized clinical trial to (1) determine the immunogenicity of a single dose of tetravalent rhesus rotavirus vaccine (RRV-TV) when administered with three different buffer regimens: no antacid buffer and small-volume (2.5-mL) and large-volume (30-mL) antacid buffer; and (2) examine the potential interference of RRV-TV on the immune response to oral polio vaccine. Immunogenicity of RRV-TV, measured as a fourfold rise in antibody titers to rotavirus, was similar in the groups receiving small- and large-dose buffer (45% and 49%, respectively) and significantly less in the group that received RRV-TV alone (23%). Administration of RRV-TV with oral polio vaccine did not significantly interfere with the neutralization response of oral polio vaccine poliovirus serotypes 1, 2, or 3, and overall, 29%, 87%, and 24% of the infants had a fourfold rise in titer to each serotype, respectively. Rotavirus vaccine could be administered most efficiently if it were incorporated into routine childhood immunizations and did not interfere with the immune response to the other vaccines, principally oral poliovirus vaccine (OPV). We conducted a placebo-controlled randomized trial giving oral rhesus rotavirus vaccine (RRV) (strain MMU 18006) alone and together with a child's first dose of OPV and diphtheria-tetanus toxoids-pertussis to examine the possible interaction of these vaccines. A total of 102 infants 2 to 3 months of age were randomized into 3 groups to receive (1) RRV with OPV, (2) placebo with OPV and (3) RRV 2 weeks after OPV. All infants were given diphtheria-tetanus toxoids-pertussis. Serum samples were collected at the time of OPV immunization and 3 to 5 weeks later. Three to 5 weeks after OPV immunization 60% of infants had a 4-fold rise in neutralization titer to at least one of the three poliovirus serotypes. The rate of antibody response to poliovirus did not differ by RRV groups but a lower rate was correlated with a shorter interval (3 vs. 5 weeks) between OPV vaccination and antibody measurement. Fifty-six percent of infants had a 4-fold rise of IgA and 62% had a 4-fold rise of neutralizing antibody to RRV; this rise did not differ according to time of OPV immunization. RRV was not associated with side effects and may be safely given with OPV to infants 2 to 3 months of age. A naturally attenuated, human neonatal strain, rotavirus vaccine candidate RV3, was tested in a limited phase II randomized double-blind controlled trial. Doses of 1 ml, containing placebo or 6.5 x 10(5) fluorescent cell forming units (fcfu) of virus in AGMK cells, were given at 3, 5 and 7 months of age. Limited replication in the small intestine is implied by the lack of virus excretion, and by the occurrence of an immune response in only 46% of the infants. However, those who developed an immune response were partially protected against rotavirus disease during the subsequent winter epidemic (protective efficacy 54%), supporting observations of protection induced by natural infection by this strain. Protection appeared to be heterotypic. Further trials are warranted, employing strategies to increase immunogenicity of this human rotavirus candidate vaccine. Orally administered rhesus rotavirus vaccine (RRV) was evaluated in a placebo-controlled study in 176 infants (ages 2 to 4 months). Eighty-eight infants received a dose of 10(4) plaque-forming units of the vaccine, and 88 received the placebo. RRV was well-tolerated but mildly reactogenic in the 10 days after vaccination. There were mild febrile reactions (greater than or equal to 38 degrees C rectally) in 40% of the vaccinees and in 16% of the placebo recipients (P = 0.001). More of the vaccinees had loose stools than did the placebo recipients (P less than 0.05). RRV was immunogenic and induced a 4-fold or greater rise in serum neutralizing antibody responses in 67% of the vaccinees; however, breast-fed infants were less likely to develop a seroresponse than infants who were not breast-fed. Despite the good immunogenicity of RRV the overall incidence of rotavirus-associated illnesses was similar between the vaccine and placebo recipients. The failure of RRV in Rochester may be related to the fact that the circulating rotaviruses were predominantly serotype 1 and RRV is a serotype 3 rotavirus. Because the serotypes of rotavirus that predominate may vary from year to year, a polyvalent preparation may be necessary to provide effective vaccination against rotaviruses. Fifty children, 3 months to 12 years of age, were given an experimental, orally administered, live attenuated rotavirus vaccine. Overall evidence of vaccine effectiveness as judged by vaccine virus shedding or a serologic response was seen in 82% of vaccinees. No clinical illness was seen in the rotavirus vaccinees when compared with 40 concurrently studied control children. No transmission to control children was observed even with close daily contact in a day-care setting. Young infants, generally less than 1 year of age, who had not previously experienced wild-type rotavirus infection shed significantly more vaccine virus. Limitation of virus shedding in those already exposed may be related to a prompt copro-IgA response which was significantly elevated by three days after vaccination. In summary, the development of this rotavirus vaccine, rhesus rotavirus-MMU-18006, is a promising step in the development of immunoprophylaxis against this major enteric pathogen. A double-blind, placebo-controlled trial of oral rhesus rotavirus vaccine at a dose of 10(4) plaque-forming units was performed in 114 young infants in Maryland. Significantly more vaccinees than controls had fever and vomiting during the week after vaccination, but these reactions were mild. Of the vaccinees, 83% had a fourfold or greater rise in neutralizing antibody to rhesus rotavirus vaccine and 69% shed vaccine virus. Seventeen percent of the vaccinees and 24% of controls had rotavirus-positive diarrhea during the 2 years of surveillance. Vaccine efficacy was therefore 29% (95% confidence limits, -31% to +66%). Stools from 12 of 13 episodes containing sufficient antigen to type were serotype 1. We conclude that rhesus rotavirus vaccine was infective, immunogenic, and probably acceptably attenuated but that this serotype 3 vaccine provided little heterotypic protection during serotype 1 outbreaks in the community. Candidate oral bovine rotavirus vaccine RIT 4237 or placebo was given to 252 Finnish infants at birth and at 7 months of age. No vaccine-associated reactions were observed. Primary rotavirus ELISA IgM responses were detected in 36% of the infants after the first vaccination; after the second dose 68% of the vaccinees were seropositive for rotavirus ELISA IgG antibody. The infants remained in clinical follow-up over two rotavirus epidemic seasons (total 28 months). Counted from child years in follow-up the overall vaccine protection rate was 43%. The clinical severity of rotavirus episodes was assessed using a numerical score 0-20. Vaccine protection rate for cases with a score greater than or equal to 7 was 57% and for cases with a score greater than or equal to 11 it was 89%. It is concluded that vaccination with a bovine rotavirus vaccine at birth and at 7 months of age, with the second dose given shortly before rotavirus epidemic season, protects infants against moderately severe and severe rotavirus diarrhoea in the first 2 years of life. Rhesus-human rotavirus reassortants incorporating the gene expressing the VP7 surface protein of human rotavirus serotypes 1 or 2, and the remaining ten genes from rhesus rotavirus (RRV) were evaluated as candidate oral vaccines in 2-4-month-old infants. A single dose of the serotype 1 reassortant vaccine which had a titre of 10(4) plaque-forming units (p.f.u.) induced a fourfold or greater antibody response in 81% of the recipients by a combination of ELISA and neutralization assays; 51% of the vaccinees developed a neutralizing antibody response to the vaccine strain. A single dose of the serotype 2 vaccine (10(4) p.f.u.) induced a seroresponse in all vaccinees by the combination of assays whereas 67% developed neutralizing antibodies to the vaccine strain. A combination of these two vaccines (0.5 x 10(4) p.f.u. of each) induced an overall seroresponse in 95% of the recipients but only 48% and 24% response in neutralizing antibodies to serotypes 1 and 2, respectively. A trivalent combination which included the two reassortants and RRV (0.33 x 10(4) p.f.u. of each strain) induced an overall response in 82% of the vaccinees, but only 30%, 20% and 65% developed a neutralizing antibody response to serotype 1, serotype 2, and RRV, respectively. Febrile reactions on days 2-5 after vaccination were seen in 23-45% of the infants receiving the various vaccines and combinations and in 5% of the placebo group. It is concluded that rhesus-human reassortant rotaviruses may be combined with each other and with RRV as a polyvalent vaccine, but the VP7-specific neutralizing antibody responses are likely to be lower after combined vaccination than following vaccination with a single reassortant rotavirus. Human rotavirus strain M37, isolated from an asymptomatic neonate, was evaluated as a live oral vaccine in a double-blinded, placebo-controlled trial involving 282 infants ages 2 to 6 months. Either 10(4) or 10(5) plaque-forming units (PFU) of the M37 vaccine were tested in 102 and 39 infants, respectively. The vaccine was well-tolerated; fever on Days 1 to 7 after vaccination was recorded in 12 and 18% of infants receiving 10(4) and 10(5) PFU of the M37 vaccine, respectively, compared with 6% of those receiving placebo; none of the vaccinees developed diarrhea. A rotavirus IgA enzyme-linked immunosorbent assay serum antibody response was detected in 47 and 76% of the infants receiving the 10(4) and 10(5) PFU vaccines, respectively. No clinical protection against rotavirus diarrhea was observed in the group vaccinated with the 10(4) PFU dose; the number of infants vaccinated with 10(5) PFU was too small for evaluation of vaccine efficacy. The M37 vaccine in a titer of 10(4) PFU was found to be inadequate; the 10(5) PFU dose was more immunogenic than the lower dose and warrants further study for clinical efficacy. The safety, immunogenicity, and efficacy of WC3 rotavirus vaccine was evaluated in a double-blind, placebo-controlled trial of healthy infants 2-12 months of age; 103 received one dose of vaccine and 103 received placebo. Vaccination appeared to be safe and induced an antibody response (WC3 neutralizing antibody) in 97% of vaccinees. Only 9 (9%) of these, however, produced antibody to human rotavirus serotypes; at least 7 of the 9 were naturally infected before vaccination. Neither the number of symptomatic episodes of rotavirus diarrhea (21 vs 25) nor the number of moderate to severe rotavirus illnesses (9 vs. 15) was significantly different in vaccine or placebo recipients, respectively, during a predominantly serotype 1 rotavirus season. A slight but significant decrease in mean symptom score was detected in vaccine recipients. Despite an overall lack of efficacy, protection could be correlated to previous rotavirus infection, high levels of WC3 neutralizing antibody, and preexisting (maternal) serotype 1 neutralizing antibody with a titer greater than or equal to 30. The objective of this study was to evaluate the efficacy of a live, attenuated bovine (strain WC3) x human (strain WI79, serotype G1) rotavirus reassortant (WI79-9) virus vaccine for prevention of symptomatic rotavirus gastroenteritis in infants. The study was a prospective, randomized, double-blind, placebo-controlled trial, conducted over a single rotavirus season in 325 infants who were 2 to 8 months old at enrollment. Subjects were randomized to receive either placebo or WI79-9 virus vaccine at 10(7.3) plaque-forming units in three oral doses each separated by 2 months. Subjects were followed for 7 days after each dose for occurrence of adverse events and during the subsequent winter for development of rotavirus gastroenteritis. Administration of WI79-9 virus vaccine was well-tolerated, and the rates of low grade fever after each dose were no higher in vaccine recipients (8 to 21%) than in placebo recipients (14 to 19%). The protective efficacy of the WI79-9 vaccine during a subsequent epidemic of predominantly serotype G1 rotavirus was 87.0% (95% confidence limits, 62.6 to 95.5%) against relatively severe rotavirus gastroenteritis (rotavirus gastroenteritis with a clinical severity score of > 8) and was 64.1% (95% confidence limits 35.9 to 79.9%) against all symptomatic rotavirus episodes. The WI79-9 vaccine was safe and effective in prevention of homotypic human rotavirus infection in infants. Further studies of reassortant vaccines based on the bovine WC3 rotavirus should be performed. We vaccinated 244 newborn infants orally with RIT 4237 bovine rotavirus vaccine or placebo and followed them serologically and clinically for 16 months. Initially 39 of the 119 (33%) vaccine recipients compared with 1 of the 120 placebo recipients seroconverted by enzyme-linked immunosorbent assay-immunoglobulin M. After the first winter rotavirus season, at 7 months of age 55% of the vaccinated infants and 37% of the unvaccinated infants were rotavirus-seropositive by enzyme-linked immunosorbent assay-immunoglobulin G (P less than 0.01, chi square test). At 12 months of age, after a low rotavirus prevalence season, 34% of the vaccinated children and 23% of the unvaccinated children remained seropositive. There were 14 confirmed episodes of rotavirus gastroenteritis in the vaccine group and 10 episodes in the placebo group during the first 16 months. However, only 1 of the episodes in the vaccine group was severe, 4 were moderately severe and 9 were mild, whereas 7 episodes in the placebo group were severe and 3 were moderately severe (P less than 0.001 between groups, Fisher's exact test). There was no clear correlation between vaccine-induced clinical protection and initial serologic response (enzyme-linked immunosorbent assay-immunoglobulin M) to vaccination, but during follow-up severe rotavirus gastroenteritis was more likely to occur in children with no serum rotavirus immunoglobulin G antibody at the time of infection. We conclude at the present stage that neonatal rotavirus vaccination with RIT 4237 vaccine gives no protection against rotavirus infection but appears to modify the severity of gastroenteritis. A single oral dose of bovine rotavirus vaccine RIT 4237 or placebo was given to 2 groups of 5-day-old infants, born in October 1984 (n = 244) and June 1985 (n = 245), who remained in follow-up for 2.8 and 2.0 years, respectively. The vaccine had no effect on the total number of detectable episodes of rotavirus diarrhoea: there were 22 cases in the vaccinees and 24 in the placebo recipients in the October group and 18 and 16 respectively in the June group. However, vaccination decreased significantly the clinical severity of rotavirus diarrhoea, as assessed by a numerical score 0-20; this vaccine effect was much greater in the infants born in October. The mean severity scores for vaccine and placebo recipients were 4.55 and 10.75 respectively in the October group (p less than 0.0001, t-test) and 8.2 and 11.6 respectively in the June group (p = 0.010, t-test). Vaccine-induced clinical protection against rotavirus diarrhoea did not correlate well with serological response after vaccination, but showed good correlation to the presence of rotavirus antibodies before the rotavirus epidemic season. It is concluded that bovine rotavirus vaccine is more efficacious when given immediately before the rotavirus epidemic season: the vaccine effect may be amplified by exposure to wild rotaviruses during the season. The safety and immunogenicity of an orally administered live human rotavirus vaccine candidate (89-12), attenuated by 33 passages in monkey kidney cells, were evaluated in placebo-controlled trials in adults, children and infants. This strain was selected because natural infections with 89-12-like rotaviruses provided 100% protection over two years. The initial evaluations in adults, seropositive children and nine infants indicated that the vaccine was safe. Two doses of vaccine (10(5) p.f.u. dose-1) or placebo were then given to 42 infants, aged from 6 to 26 weeks. No significant difference in side effects was seen. Seroconversion was demonstrated in 19 of 20 previously uninfected vaccine recipients, but > or = 4-fold rises in 89-12 neutralizing antibody titers were detected in only seven subjects. Intestinal IgA responses were detected in 15 subjects. This attenuated human rotavirus was safe and immunogenic and should be further evaluated as a vaccine candidate. The safety and protective efficacy of a serotype 1 reassortant of bovine rotavirus WC3, disignated strain WI79-9, was evaluated in a double-blind placebo-controlled trial. Rotavirus reassortant WI79-9 contains a gene segment 9 coding for the surface structural protein vp7 of a human serotype 1 rotavirus, with all other gene segments derived from WC3 rotavirus, which had previously been shown to be safe and immunogenic in infants. Infants 2-11 months of age were given two doses of vaccine (10(7.3) plaque-forming units/dose) or of placebo 28 days apart. Adverse reactions to the vaccine were not detected. The incidence of serum plaque reduction neutralization antibody responses to two doses of vaccine was serotype 6, 97%; serotype 3, 68%; and serotype 1, 22%. Active surveillance during the subsequent rotavirus season revealed 8 cases of rotavirus gastroenteritis in 39 placebo control infants and no cases in 38 WI79-9 vaccine recipients (protection = 100%, P = .003). Six cases of rotavirus gastroenteritis were caused by type 1 and two by type 3 virus. Although vaccination with WI79-9 affected only the incidence of rotavirus gastroenteritis, the vaccinated infants exhibited a significantly reduced incidence of total days of diarrhea, fever, and illness associated with gastroenteritis in general. 90 Venezuelan infants aged 10-20 weeks were randomly allocated to four groups which received one of the following: the M37 vaccine (1 x 10(4) pfu [plaque-forming units]); quadrivalent rotavirus vaccine (1 x 10(4) pfu each of serotype 3 rhesus rotavirus [RRV] and human rotavirus-RRV reassortants of serotypes 1, 2, and 4); balanced quadrivalent vaccine consisting of 1 x 10(4) pfu of serotype 1 and 3 components but 5 x 10(4) pfu of serotype 2 and 4 components; or placebo. The frequencies of transient febrile responses in these four groups were 20%, 27%, 30%, and 9%. 50% of 22 infants tested who received M37 vaccine showed a serum rotavirus IgA antibody response, compared with 74% of the 23 quadrivalent and 86% of the 22 balanced-quadrivalent recipients. 64% of the M37 recipients showed a neutralising antibody response to M37; 27% showed such responses to human serotype 1 Wa strain and 27% to serotype 4 neonatal strain ST3. 17-39% of the quadrivalent recipients and 27-41% of the balanced-quadrivalent recipients showed neutralising antibody responses to serotypes 1-4. 70-73% of the quadrivalent and balanced quadrivalent groups also showed neutralising antibody responses to RRV. The safety, infectivity, and immunogenicity of two human-bovine reassortant rotavirus candidate vaccines were evaluated in adults, children, and infants. One of these, Wa x UK, contained a single human rotavirus gene from the Wa strain that encoded VP4 P1A specificity in a background of 10 bovine genes including the VP7 gene that encodes G6 specificity, whereas the other, Wa x (DS-1 x UK), possessed the human rotavirus VP4 gene from the Wa strain as well as the human VP7 gene from strain DS-1 that encoded G2 specificity. Each of these vaccines appeared to be well-tolerated and immunogenic in infants less than 6 months of age following a single oral dose, and therefore should be evaluated further as vaccine candidates.
                Copyright 2002 Wiley-Liss, Inc. We evaluated the reactogenicity and antigenicity of a quadrivalent rotavirus vaccine composed of serotype 3 rhesus rotavirus (RRV) and three single-gene-substitution reassortants of RRV and human strain D (D x RRV, serotype 1), DS1 (DS1 x RRV, serotype 2), or ST3 (ST3 x RRV, serotype 4) in a double-masked study with 302 infants in Caracas, Venezuela. Three doses of the quadrivalent vaccine composed of either 10(5) PFU (low titer) or 10(6) PFU (high titer) of each component were administered to 99 and 101 infants, respectively, at 4-week intervals starting at the second month of age; 102 infants received a placebo. Postvaccination reactions were monitored by home visits every other day during the week postvaccination. The vaccine was associated with the occurrence of mild, short-lived febrile episodes in 26 and 23% of the recipients after the first doses of high- or low-titer vaccine, respectively, in comparison with 13% of the infants receiving the placebo. Febrile reactions occurred less frequently in vaccinees after the second or third dose than after the initial dose. The vaccine was not significantly associated with diarrhea or any additional symptom or sign. Serum specimens obtained shortly before the first, 4 weeks after the first, and 4 weeks after the third dose of vaccine or placebo were tested by an immunoglobulin A enzyme-linked immunosorbent assay and by neutralization assays. Seroresponses occurred significantly more often after 3 doses than after a single dose of either vaccine. Immunoglobulin A responses were observed in 80 and 79% of the infants after 3 doses of high- or low-titer vaccine, respectively. Most of the infants tested developed a neutralization response to RRV after 3 doses of the high- (90%) or low-(88%) titer vaccine. Neutralization response rates to human rotavirus serotypes 1 to 4 after 3 doses were similar in both vaccine and 87 of 90 receiving the high-titer vaccine developed seroresponses, as detected by any of the assays employed. The study indicates that 3 doses of quadrivalent vaccine at a titer of 10(6) PFU of each component offered no advantage over the lower-titer preparation for use in efficacy trials. In a four cell trial, a single 10(4) plaque-forming unit dose of rhesus rotavirus (RRV) vaccine (serotype G3), a human rotavirus-rhesus rotavirus reassortant vaccine with serotype G1 specificity, a similar vaccine with serotype G2 specificity, or a placebo was administered with buffer orally at 2 months of age to 800 Peruvian infants. Only the RRV vaccine was associated with a febrile response (< 38 degrees C) that occurred in 9% of the infants on day 4 after vaccination. Diarrhea or other side-effects were not associated with administration of vaccine. Vaccine strains were shed by only 12-18% of the infants as determined by examination of a single stool specimen obtained on days 4 or 5 after vaccination. Fifty per cent of vaccines developed an IgA ELISA seroresponse; however, a serotype-specific seroresponse by plaque reduction neutralization was demonstrated in < 20% of the participants against each of the three candidate vaccine strains. Vaccine efficacy was evaluated by twice-weekly home surveillance for diarrheal diseases during 24 months post-immunization. Rotavirus diarrheal episodes were identified by ELISA. Only the RRV vaccine had a significant protective efficacy (29%, p = 0.03, chi-square test) against rotavirus diarrhea. Analysis of vaccine efficacy against rotavirus episodes of any severity in which no other enteropathogen was isolated showed a trend towards higher vaccine efficacy. In addition, a similar trend was observed in rotavirus-only episodes in which there was some degree of dehydration or when health services were utilized. Serotype G1 or G2 rotavirus strains were most prevalent during surveillance. Neither serotype G1 or serotype G2 vaccines were protective against serotype 1 or 2 rotavirus diarrhea, respectively. The serotype G2 vaccine was 84% protective against serotype 1 and 2 dehydrating rotavirus diarrhea in the small numbers of individuals evaluated. We conclude that one dose of 10(4) p.f.u. of the RRV, serotype G1, or serotype G2 rotavirus vaccine failed to induce either an adequate serotype-specific seroresponse or serotype-specific protection in children immunized at 2 months of age. Only the RRV vaccine induced a low level of protection against rotavirus diarrhea mainly of serotype G1 specificity. Future studies need to explore whether higher vaccine dose and/or more than one dose would increase the immunogenicity and efficacy of the rotavirus vaccine, especially in developing countries with a high level of baseline rotavirus antibodies. nan Rotavirus is the most common cause of severe gastroenteritis among children worldwide.
                To compare the safety, immunogenicity and shedding patterns of rhesus rotavirus (RRV)-tetravalent vaccine vs. placebo among infants in rural Bangladesh.
                A double blinded, placebo-controlled trial was conducted in which infants (n = 120) were randomly assigned to receive three doses of either vaccine or placebo administered at approximately 6, 10 and 14 weeks of age together with routine immunizations. Data on possible adverse effects of vaccinations were collected daily for 7 days after each dose. Stool samples were collected after each dose, and serum samples were obtained before the first and after the third vaccination.
                Fever (> or = 38 degrees C), as measured by study assistants, was noted more frequently among vaccinees (15%) than among placebo recipients (2%) during the 7 days after vaccination but was not reported more frequently by parents of vaccinees vs. placebo recipients. Overall 87% of vaccinees had an antibody response (measured by IgA or anti-RRV-neutralizing antibodies) after vaccination compared with 32% of placebo recipients. Rates of seroconversion were higher among subjects with lower levels of prevaccination antibodies and those who shed rotavirus after vaccination. Vaccine strain viruses were detected in stools from placebo vaccine recipients who had evidence of IgA seroconversion.
                In this population RRV-tetravalent vaccine was comparably immunogenic and safe as in trials conducted in developed countries, where this vaccine has been proved effective in preventing severe rotavirus diarrhea. These data support continued evaluation of rotavirus vaccines in developing countries. A tetravalent rhesus-human reassortant rotavirus (RRV-TV) vaccine (4 x 10(4) plaque-forming units/dose) was evaluated for safety, immunogenicity and efficacy in a prospective, randomized, double-blind, placebo-controlled trial involving 540 Brazilian infants. Doses of vaccine or placebo were given at ages 1, 3 and 5 months. No significant differences were noted in the occurrence of diarrhoea or vomiting in vaccine and placebo recipients following each dose. Low-grade fever occurred on days 3-5 in 2-3% of vaccinees after the first dose, but not after the second or third doses of vaccine. An IgA antibody response to rhesus rotavirus (RRV) occurred in 58% of vaccinees and 33% of placebo recipients. Neutralizing antibody responses to individual serotypes did not exceed 20% when measured by fluorescent focus reduction, but exceeded 40% when assayed by plaque reduction neutralization. There were 91 cases of rotavirus diarrhoea among the 3-dose (vaccine or placebo) recipients during two years of follow-up, 36 of them among children given the vaccine. Overall vaccine efficacy was 8% (P = 0.005) against any diarrhoea and 35% (P = 0.03) against any rotavirus diarrhoea. Protection during the first year of follow-up, when G serotype 1 rotavirus predominated, was 57% (P = 0.008), but fell to 12% in the second year. Similar results were obtained when analysis was restricted to episodes in which rotavirus was the only identified pathogen. There was a tendency for enhanced protection by vaccine against illness associated with an average of 6 or more stools per day. These results are sufficiently encouraging to warrant further studies of this vaccine in developing countries using a higher dosage in an attempt to improve its immunogenicity and efficacy. A randomised, double-blind, placebo-controlled trial was conducted to evaluate the ability of RIT 4237 live attenuated bovine rotavirus (subgroup 1) vaccine strain to protect against natural rotavirus infection in children. 178 infants aged 8 to 11 months received a single oral dose of RIT 4237 vaccine or placebo and were followed up serologically and clinically during a subgroup 2 rotavirus epidemic. No side-effects attributable to the vaccine were observed. During the 5 months' observation after vaccination 2 of the 86 vaccine recipients and 18 of 92 placebo recipients had rotavirus diarrhoea lasting more than 24 h (p less than 0.001). The vaccine-protection rate was thus 88%. The 2 children in the vaccine group with rotavirus diarrhoea were regarded as primary vaccine failures since they had no detectable serum antibody responses after vaccination. Vaccine prepared from RIT 4237 strain of attenuated bovine rotavirus thus seems to protect children against heterologous subgroup 2 rotavirus diarrhoea. To compare the safety and immunogenicity of two dosages of tetravalent rhesus rotavirus vaccine (RRV-TV) and the effect of age at dosing.
                A total of 195 infants were stratified by age into 2 groups, 6 to 12 weeks and 16 to 24 weeks, and randomly assigned to receive a single dose of placebo or RRV-TV containing either 4 x 10(5) or 4 x 10(6) plaque-forming units (pfu). Symptoms were recorded for 5 days after vaccination. Anti-rotavirus IgA and neutralizing antibody to human rotavirus serotypes G1 to G4 and RRV were measured in serum obtained pre- and postvaccination.
                Rates of fever > 38 degrees C (9%), diarrhea (6%) and vomiting (8%) were similar in all groups. IgA (69% vs. 49%, P = 0.02) and RRV (85% vs. 66%, P = 0.004) seroconversion rates were significantly higher in the 4 x 10(6) pfu vaccine group as were antibody titers to RRV (440.2 vs. 263.7, P = 0.04). Older infants demonstrated significantly higher seroconversion rates and antibody titers for IgA (71% vs. 52%, P = 0.03; and 110.6 vs. 54.8, P = 0.004) and RRV (92% vs. 66%, P = 0.05 and 498.3 vs. 205.6, P = 0.01) at either dose level than did the younger infants. There were no significant differences in seroconversion rates or antibody titers to human rotavirus types G1 to G4 between the two vaccination groups.
                RRV-TV at a dose of 4 x 10(6) pfu can be safely administered to infants 6 to 24 weeks of age. A single dose of 4 x 10(6) pfu of RRV-TV was significantly more immunogenic than a single dose of 4 x 10(5) pfu but did not improve responses to the human serotypes. Older vaccine recipients demonstrated significantly higher IgA and neutralizing antibody seroconversion rates and antibody titers than younger infants independent of dosage. nan Rhesus rotavirus oral vaccine strain MMU 18006 at a dose of 10(5) plaque-forming units (PFU), a 1:10 dilution of the original undiluted vaccine, is highly immunogenic in young children. Fevers have occurred, however, on Days 3 and 4 following vaccination. This study was conducted to determine whether febrile reactions could be eliminated and immunogenicity maintained by (1) giving smaller doses of vaccine or (2) vaccinating younger infants. Thirty-one children between 3 and 11 months of age received, in a randomized, double blind manner, either 10(4) PFU of vaccine virus, 10(3) PFU of vaccine virus or placebo. All recipients of the 10(4) PFU dose had a seroresponse; however, some degree of immunogenicity was lost with the smaller dose (10(3) PFU). Fevers were observed in recipients of both of the lowered doses of vaccine but the febrile reactions were related to the age of the vaccinee. No infant younger than 5 months of age experienced a temperature elevation, whereas the majority of children older than 5 months had fevers. Our data suggest that the lack of reaction in the younger infants correlates with the presence of prevaccination neutralizing antibody, presumably transplacentally acquired. We conclude that the rhesus rotavirus oral vaccine at a dose of 10(4) PFU is immunogenic and appears to be safe in young infants. A randomized, double-blind trial was performed to assess serological response and clinical protection for acute gastroenteritis due to rotavirus in 103 children aged 6 to 18 months, after a single dose of RIT 4237 live attenuated bovine rotavirus vaccine or placebo. Seroconversion, determined by enzyme-linked immunoabsorbent assay (ELISA), was significantly greater in initially seronegative vaccines compared with control group (p less than 0.0001); clinical protection rate was low in this study group and it is therefore concluded that seroconversion by itself is not sufficient to measure vaccine efficacy. Phase I studies of an oral quadrivalent rotavirus vaccine were conducted in 130 Venezuelan infants 10 to 20 weeks of age. The vaccine consists of a mixture of equal amounts of rhesus rotavirus (RRV) vaccine (serotype 3 [VP7]) and each of three human rotavirus-RRV reassortant strains: D x RRV (serotype 1 [VP7]), DS1 x RRV (serotype 2 [VP7]), and ST3 x RRV (serotype 4 [VP7]). Three different doses of the quadrivalent vaccine (0.25 x 10(4), 0.5 x 10(4), and 10(4) PFU of each component) were evaluated sequentially for safety and antigenicity in placebo-controlled, double-blind trials. Starting the day after vaccination, the infants were monitored by daily home visits for 7 days. Only minor reactions were observed during this period; these were limited to mild transient febrile episodes which began day 2 or 3 after vaccination and lasted 1 to 2 days in 15 to 30% of the infants. Serological studies demonstrated that 68 to 96% of the infants developed a rotavirus serum immunoglobulin A response following vaccination. However, when tested by plaque reduction neutralization assay against individual human rotavirus serotype 1, 2, 3, or 4, the response rates ranged from 4 to 23% with the low dose, 21 to 33% with the medium dose, and 32 to 58% with the high dose. Most (73 to 79%) infants developed neutralizing antibodies to RRV following administration of each dose schedule. Vaccine virus shedding was analyzed by utilizing tissue culture isolation of virus from stool. All of the infants who received the lower of medium dose and 89% of those fed the high dose shed one or more components of the vaccine. Analyses of rotavirus serotypes isolated from the stool of infants who received the 0.25 x 10(4) -PFU dose revealed that DS1 x RRV was the most commonly shed vaccine component, followed by RRV, D x RRV, and ST3 x RRV in that order. The efficacy of a rhesus rotavirus vaccine (MMU 18006, serotype 3) against infantile diarrhea was evaluated by active home surveillance of a group of 320 children 1-10 months of age in Caracas, Venezuela. During a 1 year period following oral administration of vaccine or placebo under a double-masked code, over 600 diarrheal episodes were detected. Etiologic studies revealed that heat-stable toxin (ST) producing enterotoxigenic E. coli (ETEC) was the most common diarrheal agent detected (34%) followed by enteropathogenic E. coli (EPEC, 10.9%), heat-labile toxin (LT) producing ETEC (7.6%), rotavirus (6.9%), Cryptosporidium (4.8%) and Campylobacter (1.3%). ST-producing ETEC were also recovered from over 20% of control stool specimens obtained during diarrhea-free periods, whereas EPEC, rotavirus, Cryptosporidium, and Campylobacter were rarely detected in such control specimens. Rotavirus was responsible for about one-half of the more severe cases of diarrhea. Twenty-two of 151 infants who received placebo (14.6%) and eight of 151 receiving a 10(4) PFU dose of vaccine (5.3%) had rotavirus diarrhea during the follow-up period for an efficacy level of 64% against any rotavirus diarrhea. However, vaccine efficacy reached 90% against the more severe cases of rotavirus diarrhea and was noticeably high in the 1-4 month age group. Serotypic analysis of the rotaviruses detected suggests that the resistance induced by the vaccine was type specific since significant protection was only evident against serotype 3 rotaviruses. A 10(3) PFU dose tested initially in 18 children did not appear to protect against rotavirus diarrhea. To assess safety and immunogenicity, 213 healthy infants aged 6 weeks to 4 months were randomized to receive a single dose of placebo, a 10(4) or 10(5) p.f.u. dose of rhesus rotavirus (RRV) serotype 3, human-RRV reassortant (VP-7 serotypes 1, 2 or 4) or a 10(4) or 10(5) p.f.u. dose of tetravalent rotavirus vaccine (containing equal parts of serotype 1, 2, 3 and 4 strains). The infants were fed ad libitum before and after vaccination; no buffer was used. For 7 days after vaccination, potential vaccine side effects were monitored, and no significant differences were noted for any symptom evaluated among the single serotype, tetravalent or placebo groups. Sera, obtained before and 28 days after vaccination, were measured for antibody to rotavirus by IgG, IgA and IgM enzyme-linked immunosorbent assay in all subjects, and by neutralizing antibody to the individual serotypes by plaque reduction in placebo and tetravalent vaccinees. The serological response rates for serotypes 1, 2, 3, 4 and the tetravalent vaccine were 25, 12, 19, 11 and 22%, respectively, at 10(4) p.f.u.; 47, 50, 35, 29 and 61%, respectively, at 10(5) p.f.u.; and 37% for placebo. The tetravalent vaccine was more immunogenic at 10(5) than at 10(4) p.f.u. (p = 0.04). Grouped together, the vaccines at 10(5) p.f.u. (single serotype and tetravalent) were more immunogenic than the vaccines at 10(4) p.f.u. (38 of 85 versus 17 of 94 seroresponders; p < 0.001).(ABSTRACT TRUNCATED AT 250 WORDS) Ninety-six healthy infants ages 2 to 5 months received rhesus rotavirus vaccine serotype 3 (RRV) as a single dose of 10(3), 10(4) or 10(5) plaque-forming units (pfu) in this double-blinded, placebo-controlled study. Half of the infants in each dose group were also randomized to receive either 30 ml of infant formula as buffer before vaccination or were vaccinated on an empty stomach. The incidence of fever, increased stool frequency and decreased activity level was consistently higher among infants who received RRV than those who received placebo. There was no consistent increase in incidence of symptoms as the dose of RRV was increased. Possible vaccine-related side effects were increased in older vaccinees and in those with higher pre-vaccination antibody titers. The seroconversion rate and pre to postvaccination antibody rise, evaluated by enzyme-linked immunosorbent assay and by plaque reduction neutralization, correlated well. The 10(5) and 10(4) pfu RRV dose produced significantly higher rates of seroconversion and higher antibody rises than did placebo (P less than 0.001 for 10(5) and P = 0.005 for 10(4]. The 10(3) pfu dose was no more immunogenic than placebo. In the 10(4) pfu dose group 73% of infants receiving formula as a "buffer" seroconverted compared with 36% of those not receiving formula; 63% of infants partially breast-fed or formula-fed seroconverted compared with 17% of those exclusively breast-fed. These differences in seroconversion rate were largely overcome by increasing the RRV dose to 10(5) pfu. Stool (copro IgA) antibody responses were examined; of six infants showing a copro IgA response only one had seroconverted based on enzyme-linked immunosorbent assay or plaque reduction neutralization. RRV was recovered by tissue culture more frequently from the stool in those infants who received RRV 10(5) and 10(4) pfu than among those receiving 10(3) pfu or placebo (P less than 0.001). The reactogenicity and antigenicity of the rhesus rotavirus vaccine, strain MMU18006, developed at the Laboratory of Infectious Diseases (National Institute of Allergy and Infectious Diseases, National Institutes of Health) were examined in a double blind, placebo-controlled study of 40 newborn infants in Caracas, Venezuela. The children were observed for the first few days after birth in the hospital nursery and by home visits for 10 days after vaccination to detect any adverse reactions. No reactions could be attributed to the vaccine. Serologic responses to the vaccine were evaluated in paired sera obtained at birth (cord blood) and 4 weeks after vaccination. Serologic responses to the vaccine were not observed by complement fixation, neutralization or a rhesus rotavirus VP7 epitope-specific competition assay. However, such responses were found in 9 of 14 tested infants by an immunoglobulin A-specific enzyme-linked immunosorbent assay. Seventeen of the 20 vaccinees also shed rhesus rotavirus vaccine in stool during the postvaccination period. nan To determine the safety and relative efficacy of two reassortant rhesus rotavirus vaccines over two rotavirus seasons.
                A prospective, double-masked, placebo-controlled trial.
                Twenty-three centers in the United States.
                A total of 1006 healthy infants between 4 and 26 weeks of age were enrolled, and 898 received three doses of vaccine or placebo.
                Reactogenicity was determined by comparing the incidence of fever, diarrhea, and/or vomiting for 5 days after each dose of vaccine. Rotavirus IgA and neutralizing antibody to rhesus rotavirus and four rotavirus serotypes were measured in a subset of subjects. Relative efficacy was determined by comparing the incidence of rotavirus gastroenteritis after three doses of vaccine or placebo over two rotavirus seasons.
                Adverse reactions were mild and limited to a small but significant increase in the incidence of fever after the first dose of tetravalent but not monovalent vaccine. The relative efficacy against rotavirus disease over the 2 years of observation was 40% (98.3% confidence interval, 7% to 62%) for the monovalent and 57% (98.3% confidence interval, 29% to 74%) for the tetravalent vaccine. In post hoc analyses, the relative efficacy against very severe rotavirus gastroenteritis was 73% and 82% for monovalent and tetravalent vaccine recipients, respectively. Also, a 67% and 78% reduction in medical visits for rotavirus gastroenteritis was observed. Both vaccines protected against disease caused by serotype 1 rotavirus, but only the tetravalent vaccine reduced the incidence of disease caused by non-serotype 1 rotavirus infection detected in the second season. It is unclear, however, whether this result represents serotype-specific protection or a difference in the duration of protection.
                Vaccination with both vaccines was safe and significantly reduced the incidence of rotavirus gastroenteritis, but only the tetravalent vaccine provided protection against disease caused by non-serotype 1 rotaviruses during the second year of follow-up. A randomized placebo-controlled double-blind field trial of RIT 4237 attenuated rotavirus vaccine in Lima, Peru, evaluated the protection against diarrheal illness by one, two, or three doses of vaccine. There were 391 children, 2-18 months old, studied for the occurrence of diarrhea during the 18 months after vaccination. Three doses of the vaccine provided 40% protection against any diarrheal illness associated with rotavirus alone but 58%-75%; protection against the more severe rotaviral illnesses. The vaccine appeared to be more efficacious when it was administered to children in the first year of life. Three doses provided up to 89% efficacy against more severe diseases due to serotype 1 rotavirus, and one dose also afforded significant protection. The protection was lower, even with three doses, against serotype 2 rotavirus. This vaccine trial has provided important insights on how such trials should be conducted and on the serotype-specificity of protection from rotavirus infection. Future vaccines should be able to protect against severe disease caused by all rotavirus serotypes and must work in developing countries where rotavirus is the most important cause of diarrheal mortality. To conduct a phase 1 safety and tolerability trial of an oral rotavirus vaccine candidate RV3 in healthy volunteers.
                Double blind placebo controlled trial of a single 1 mL oral dose (6.5 x 10(5) fluorescing focus units [FFU]/mL) in 10 healthy young men, 10 3-4 year old children and 10 3 month old infants with a 4 week surveillance period. The study was undertaken at a children's hospital and nearby community in Melbourne, Australia.
                All subjects successfully completed the trial. There were no significant side-effects attributable to the vaccine preparation in any age group. No shedding of vaccine virus was detected by enzyme immunoassay. There was evidence of an immune response in serum and/or gut secretions in two of five vaccinees in each age group.
                RV3 rotavirus vaccine appears to be safe and well tolerated. Evidence of immunogenicity in some subjects after a single dose encourages further trials to determine immunogenicity after three doses, after reduction of viral dose, and without prior administration of buffer. Rhesus-human rotavirus (RV) reassortant vaccine strains D x RRV or DS 1 x RRV with VP7 serotype 1 or 2 specificity were evaluated for safety, immunogenicity and protective efficacy in a double blind placebo-controlled three cell trial involving 359 infants ages 2 to 5 months. The titer of the D x RRV vaccine was 10(4) and that of the DS 1 x RRV vaccine was 10(5) plaque-forming units/1-ml dose. The vaccines were acceptably reactogenic, each inducing a transient febrile response in fewer than one-third of the vaccinees. Seroconversion by RV enzyme-linked immunosorbent assay IgA antibody was detected in 61 and 75% of the vaccinees receiving a single dose of the serotype 1 or 2 reassortant vaccine, respectively. Efficacy against RV diarrhea was evaluated in two successive epidemic seasons; RV serotype 1 was prevalent in both. Clinical efficacy was observed with both vaccines and was associated with seroconversion after vaccination; considering only such vaccinees both vaccines showed equal efficacy. The overall rates of protection for the two vaccines combined against clinical RV disease in children with seroconversion after vaccination were 92 and 59% in the first and second RV epidemic seasons, respectively. Protection against asymptomatic RV infection, as measured by serologic responses, was 59% in the first season and nil in the second season. It is concluded that each of the reassortant RV vaccines was effective in inducing protection against symptomatic RV disease associated with RV serotype 1. Live rotavirus vaccine candidates representing VP7 serotypes 1, 2, 3 or 4 derived by reassortment between bovine UK rotavirus and human rotavirus strains D, DS-1, P or ST3 were evaluated for safety and immunogenicity in adults, children and infants. Infection was defined by evidence of rotavirus shed in stools or a 4-fold or greater increase in serum rotavirus-specific IgA or IgG ELISA or plaque reduction neutralization antibody. A single oral dose (10(5.3) or 10(5.8) pfu) of reassortant virus was well tolerated and infected most infants: 10/20 (50%) by D x UK; 9/11 (82%) by DS-1 x UK; 8/10 (80%) by P x UK and 13/14 (93%) by ST3 x UK. All 14 infants given two doses of D x UK were infected. These findings demonstrating satisfactory levels of attenuation, safety, infectivity and immunogenicity of each reassortant in infants warrant additional studies of a candidate vaccine containing these four strains. In a double blind placebo-controlled study rotavirus vaccine RIT 4237 was offered to young infants after the fourth week of life. The vaccine was very well tolerated. Fifty-seven out of 100 vaccine recipients and 10 out of 103 placebo recipients developed rotavirus-IgM-antibodies during the 1 month follow-up period. During a 6 month follow-up, stool samples from 2 out of 12 vaccinees and from 5 out of 12 placebo recipients contained rotavirus. We compared the efficacy, safety, and immunogenicity of a rhesus rotavirus tetravalent vaccine (RRV-TV), a rhesus rotavirus monovalent (serotype 1) vaccine (RRV-S1), and placebo in healthy American Indian infants for two rotavirus seasons.
                Infants aged 6 to 24 weeks were enrolled in a randomized, double-blind efficacy study. Infants were orally administered RRV-TV (4 x 10(5) plaque-forming units per dose), RRV-S1 (4 x 10(5) plaque-forming units per dose), or placebo at 2, 4, and 6 months of age. Stools collected during episodes of gastroenteritis were tested for detection of rotavirus antigen. A total of 1185 infants received at least one dose of a study vaccine or placebo, and 1051 received all three doses according to the protocol.
                During the first year of surveillance, the estimates of vaccine efficacy (with 95% confidence interval) for preventing rotaviral gastroenteritis were 50% (26, 67) for RRV-TV and 29% (-1, 50) for RRV-S1. In this population only 6% of rotaviral gastroenteritis episodes among placebo recipients were associated with type G1 disease. For severe disease the estimates of vaccine efficacy were higher: 69% (29, 88) for RRV-TV and 48% (-4, 75) for RRV-S1.
                These data indicate that RRV-TV is moderately efficacious in preventing all episodes of gastroenteritis caused by rotavirus and is most efficacious against the severe disease characteristic of rotaviral illness. Heterologous live, oral rotavirus vaccines of rhesus monkey (RRV-1) and bovine (RIT 4237) origin were tested for immunogenicity, excretion of virus, and clinical reactions in six- to eight-month-old infants. Antibody response, indicating infection with the vaccine virus, was detected in 21 (88%) of 24 children receiving the RRV-1 vaccine and in 18 (75%) of 24 receiving the RIT 4237 vaccine. Excretion of virus in the stools within one week after vaccination was demonstrable in 84% of the RRV-1 and in 21% of the RIT 4237 vaccinees. RRV-1 vaccination was associated with a febrile response (over 38 C) that clustered on days 3 or 4 postvaccination in 64% of the recipient children. In addition, 20% of the RRV-1 vaccinees had watery stools on days 4 or 5. Fever on days 3 and 4 and loose stools were not seen in the RIT 4237 vaccinees. We concluded that in young children the RRV-1 (rhesus monkey) rotavirus vaccine is more immunogenic than the RIT 4237 (bovine) rotavirus vaccine, but vaccination with RRV-1 is associated with significant adverse reactions. In a randomized, double-blind, placebo-controlled trial, 331 infants aged 6 to 12 months received orally, at an interval of 1 month, either two doses of live attenuated bovine rotavirus vaccine strain RIT 4237 or equivalent placebo. The vaccinations were carried out during September to November, a non-rotavirus season; only three cases of rotavirus diarrhea occurred in the study group before the vaccinations were completed. During the epidemic season from December to May, 31 patients with clinically significant rotavirus diarrhea required therapy. Five of these were among the 168 vaccine recipients, and 26 among the 160 placebo recipients (P less than 0.001), giving a vaccine protection rate of 82%. The incidence of clinically significant diarrhea from all causes was reduced by 76% in the vaccinees. As determined by an enzyme immunoassay antibody test with homologous virus antigen, seroconversion after vaccination was obtained in 53% of the initially seronegative infants. Clinical protection correlated well with seroconversion, but the vaccinees who failed to seroconvert also had less rotavirus diarrhea than the placebo recipients, suggesting that immunity may be mediated by factors other than serum EIA antibody. Seventeen of the 23 rotavirus isolates in the epidemic season that were typed were of serotype 1, two were of serotype 2, and four were of serotype 3. The protection rates against clinically significant diarrhea were 72%, 100%, and 100% for serotypes 1, 2, and 3, respectively. We conclude that epidemic infantile winter diarrhea associated with human rotaviruses can be significantly reduced by vaccination with the live attenuated RIT 4237 bovine rotavirus vaccine before the epidemic season. To investigate the incorporation of oral rhesus-human reassortant rotavirus tetravalent (RRV-TV) vaccine into a routine immunization programme, RRV-TV or oral placebo was coadministered with a pentavalent diphtheria-tetanus-whole-cell pertussis-Haemophilus influenzae b (Hib)-inactivated polio vaccine and hepatitis B vaccine following a 3-4-5-mo schedule in a double-blind trial involving 249 infants. Seroconversion rates after 3 doses of rotavirus vaccine were 80% for rotavirus immunoglobulin A (IgA) and 93% for RRV neutralizing antibodies. Rotavirus vaccine did not interfere with the immune responses to diphtheria, tetanus, pertussis, Hib, poliovirus 1, 2 and 3, or hepatitis B. Following the first, second and third doses of vaccine, fever >38 degrees C on the day of vaccination was seen in 31%, 24% and 24%, respectively, with no difference between RRV-TV- and placebo-vaccinated children. This fever was presumably due to the whole-cell pertussis vaccine. Those vaccinees who received concomitant RRV-TV vaccine had another peak of fever around d 4 after the first dose, when 25% of them had fever >38 degrees C and 3% >39 degrees C. It is concluded that RRV-TV rotavirus vaccine can be given concurrently with other childhood immunizations following a 3-4-5-mo vaccination schedule. However, febrile reactions to RRV-TV rotavirus vaccine are common when the first dose is given at the age of 3 mo.
Current evidence shows that rhesus rotavirus vaccines (particularly RRV-TV) and the human rotavirus vaccine 89-12 are efficacious in preventing diarrhoea caused by rotavirus and all-cause diarrhoea. Evidence about safety, and about mortality or prevention of severe outcomes, is scarce and inconclusive. Bovine rotavirus vaccines were also efficacious, but safety data are not available. Trials of new rotavirus vaccines will hopefully improve the evidence base. Randomized controlled trials should be performed simultaneously in high-, middle-, and low-income countries.

2010 Editor's Note: Several of the vaccines investigated in this review are no longer in routine clinical use (for example, live attenuated rhesus-human reassortant tetravalent vaccine) and further new vaccines have been tested and approved for use since this review was written in 2004. For an up-to-date assessment of rotavirus vaccines currently approved for use, please see : Soares-Weiser K, MacLehose H, Ben-Aharon I, Goldberg E, Pitan F, Cunliffe N. Vaccines for preventing rotavirus diarrhoea: vaccines in use. Cochrane Database of Systematic Reviews 2010, Issue 5. Art. No.: CD008521. DOI: 10.1002/14651858.CD008521.