Immunogenicity, reactogenicity and safety of a human rotavirus vaccine (RIX4414) in Korean infants: A randomized, double-blind, placebo-controlled, phase IV study Safety, immunogenicity, and excretion pattern of single-dose live oral cholera vaccine CVD 103-HgR in Peruvian adults of high and low socioeconomic levels. Successful co-administration of a human rotavirus and oral poliovirus vaccines in Bangladeshi infants in a 2-dose schedule at 12 and 16 weeks of age. Safety and efficacy of an attenuated vaccine against severe rotavirus gastroenteritis. Serologic correlates of immunity in a tetravalent reassortant rotavirus vaccine trial. US Rotavirus Vaccine Efficacy Group. Efficacy, safety and immunogenicity of RIX4414 in Japanese infants during the first two years of life. Efficacy of human rotavirus vaccine against severe gastroenteritis in Malawian children in the first two years of life: a randomized, double-blind, placebo controlled trial. 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. Immunogenicity of the pentavalent rotavirus vaccine among infants in two developing countries in Asia, Bangladesh and Vietnam. A dose-escalation safety and immunogenicity study of live attenuated oral rotavirus vaccine 116E in infants: a randomized, double-blind, placebo-controlled trial. Immunogenicity, reactogenicity and safety of the human rotavirus vaccine RIX4414 oral suspension (liquid formulation) in Finnish infants. Efficacy of human rotavirus vaccine against rotavirus gastroenteritis during the first 2 years of life in European infants: randomised, double-blind controlled study Experience of pentavalent human-bovine reassortant rotavirus vaccine among healthy infants in Taiwan. 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. Lack of correlation between serum rotavirus antibody titers and protection following vaccination with reassortant RRV vaccines. US Rotavirus Vaccine Efficacy Group. Immunogenicity and safety of the human rotavirus vaccine Rotarix co-administered with routine infant vaccines following the vaccination schedules in Europe. Efficacy of the oral pentavalent rotavirus vaccine in Mali. Safety and efficacy of a pentavalent human-bovine (WC3) reassortant rotavirus vaccine. Efficacy of pentavalent rotavirus vaccine against severe rotavirus gastroenteritis in infants in developing countries in Asia: a randomised, double-blind, placebo-controlled trial Efficacy and immunogenicity of two or three dose rotavirus-vaccine regimen in South African children over two consecutive rotavirus-seasons: a randomized, double-blind, placebo-controlled trial. Vaccine desirability during an effectiveness trial of the typhoid fever polysaccharide Vi vaccine, Kolkata India Analyses of health outcomes from the 5 sites participating in the Africa and Asia clinical efficacy trials of the oral pentavalent rotavirus vaccine. Efficacy and safety of an oral live attenuated human rotavirus vaccine against rotavirus gastroenteritis during the first 2 years of life in Latin American infants: a randomised, double-blind, placebo-controlled phase III study Immunogenicity of the pentavalent rotavirus vaccine in African infants. Immunogenicity, reactogenicity and safety of the human rotavirus vaccine RIX4414 (Rotarix™) oral suspension (liquid formulation) when co-administered with expanded program on immunization (EPI) vaccines in Vietnam and the Philippines in 2006-2007. Concomitant Use of the Oral Pentavalent Human-Bovine Reassortant Rotavirus Vaccine and Oral Poliovirus Vaccine Efficacy of pentavalent rotavirus vaccine against severe rotavirus gastroenteritis in infants in developing countries in sub-Saharan Africa: a randomised, double-blind, placebo-controlled trial Safety and efficacy of human rotavirus vaccine during the first 2 years of life in Asian infants: randomised, double-blind, controlled study. Comparison of 2 different regimens for reactogenicity, safety, and immunogenicity of the live attenuated oral rotavirus vaccine RIX4414 coadministered with oral polio vaccine in South African infants.
Rotavirus ( RV ) infection is the primary cause for childhood gastroenteritis worldwide . In Korea , RV infection is most common among children less than 5 y of age . This post-licensure study was conducted to further evaluate the RV vaccine ( RIX4414 ) to provide additional local clinical data to the Korean Food and Drug Association . Healthy infants aged 6–12 weeks were enrolled to receive two doses of either RIX4414 or placebo as per 0 , 1–2 mo schedule . Blood sample s were collected before dose-1 and one month post-dose-2 of RIX4414/placebo to assess serum anti-RV IgA antibody concentrations using ELISA . Gastroenteritis stool sample s were tested for the presence of RV using ELISA . RV positive sample s were subjected to further analysis for G and P typing . Among 684 infants enrolled and vaccinated , 432 infants ( RIX4414 = 318 ; placebo = 114 ) were included in the according-to- protocol cohort for immunogenicity . The anti-RV IgA antibody seroconversion rates in the RIX4414 group following one month post-dose-2 were 88.1 % ( 95 % CI : 84.0–91.4 ) and the corresponding geometric mean concentration in the RIX4414 group was 208.5 U/ml ( 95 % CI : 174.2–249.5 ) . Occurrence of solicited and unsolicited adverse events were similar in both , RIX4414 and placebo groups . None of the gastroenteritis stool sample s tested positive for RV and no fatal SAEs were reported in either groups . The two-dose regimen of RIX4414 was observed to be immunogenic with a similar safety profile as compared with the placebo group , when administered to healthy Korean infants Groups of 122 Peruvian adults of low socioeconomic level ( SEL ) and 125 of high SEL received a r and omly allocated 5 x 10(9)- or 5 x 10(8)-CFU dose of CVD 103-HgR live oral cholera vaccine or a placebo . The vaccine was well tolerated . Vibriocidal seroconversions occurred in 78 % of high-SEL and 72 % of low-SEL subjects who ingested the high dose and in 78 and 49 % , respectively , of those who received the low dose Co-administration of oral live-attenuated human rotavirus vaccine RIX4414 ( Rotarix ) and oral polio vaccine ( OPV ) was assessed . Healthy infants were r and omised to receive 2-doses of either : RIX4414 or placebo co-administered with OPV ( 12 and 16 weeks of age ) ; or RIX4414 or placebo given 15 days after OPV . After vaccination , 56.5 - 66.7 % of RIX4414 and 18.6 % of placebo recipients had seroconverted for rotavirus IgA. No significant differences between RIX4414 groups with or without OPV co-administration were observed . No statistically significant differences were observed between groups for polio seroprotection rates . RIX4414 vaccine was immunogenic when co-administered with OPV and did not interfere with OPV seroprotection rates BACKGROUND The safety and efficacy of an attenuated G1P[8 ] human rotavirus ( HRV ) vaccine were tested in a r and omized , double-blind , phase 3 trial . METHODS We studied 63,225 healthy infants from 11 Latin American countries and Finl and who received two oral doses of either the HRV vaccine ( 31,673 infants ) or placebo ( 31,552 infants ) at approximately two months and four months of age . Severe gastroenteritis episodes were identified by active surveillance . The severity of disease was grade d with the use of the 20-point Vesikari scale . Vaccine efficacy was evaluated in a subgroup of 20,169 infants ( 10,159 vaccinees and 10,010 placebo recipients ) . RESULTS The efficacy of the vaccine against severe rotavirus gastroenteritis and against rotavirus-associated hospitalization was 85 percent ( P<0.001 for the comparison with placebo ) and reached 100 percent against more severe rotavirus gastroenteritis . Hospitalization for diarrhea of any cause was reduced by 42 percent ( 95 percent confidence interval , 29 to 53 percent ; P<0.001 ) . During the 31-day window after each dose , six vaccine recipients and seven placebo recipients had definite intussusception ( difference in risk , -0.32 per 10,000 infants ; 95 percent confidence interval , -2.91 to 2.18 ; P=0.78 ) . CONCLUSIONS Two oral doses of the live attenuated G1P[8 ] HRV vaccine were highly efficacious in protecting infants against severe rotavirus gastroenteritis , significantly reduced the rate of severe gastroenteritis from any cause , and were not associated with an increased risk of intussusception . ( Clinical Trials.gov numbers , NCT00139347 and NCT00263666 . The correlation of antibody responses ( serum rotavirus IgA and neutralizing antibody to serotype G1-G4 human rotaviruses and rhesus rotavirus [ RRV ] ) in a reassortant rotavirus vaccine trial with protection against rotavirus infection or disease was investigated . Most subjects administered 4 x 10(5 ) pfu of either the serotype G1 monovalent or serotype G1-G4 tetravalent vaccine seroconverted for at least one of the six antibodies ( 85 % and 91 % , respectively ) . However , fewer than one-third seroconverted to any prototype G1-G4 human rotavirus . Analyses of covariance indicated that higher prevaccination neutralizing antibody titers negatively affected postvaccination titers . Significant relationships were found between several postvaccination rotavirus antibody titers and protection , and serotype-specific correlates of protection were identified between anti-Wa titers and G1 illnesses ( P = .03 ) and between anti-RRV titers and G3 illnesses ( P < .001 ) . Overall , however , serotype-specific immunity was no more significant than heterotypic immunity , and no specific titer of any antibody analyzed was a reliable indicator of protection A phase III , r and omized , double-blind study evaluated the efficacy , reactogenicity , safety and immunogenicity of a human rotavirus vaccine , RIX4414 in Japanese infants aged 6 - 14 weeks when administered as two doses ( 0 , 1-month schedule ) . Efficacy against any and severe rotavirus gastroenteritis leading to medical intervention caused by circulating wild-type rotavirus from two weeks post-Dose 2 until two years of age was 79.3 % ( 95 % CI : 60.5 - 89.8 % ) and 91.6 % ( 95 % CI : 62.4 - 99.1 % ) , respectively . Solicited , unsolicited symptoms and serious adverse events were reported at a similar frequency in both groups . Serum anti-rotavirus antibody seroconversion rate one-month post-Dose 2 was 85.3 % ( 95 % CI : 68.9 - 95 % ) in RIXX4414 group . RIX4414 was efficacious , well-tolerated and immunogenic in Japanese infants and introduction of vaccination could help in reducing the disease burden Rotavirus gastroenteritis is a major cause of morbidity and mortality among African infants and young children . A phase III , placebo-controlled , multi-centre clinical trial of a live , oral G1P[8 ] human rotavirus vaccine ( RIX4414 ) undertaken in Malawi and South Africa significantly reduced the incidence of severe rotavirus gastroenteritis in the first year of life . We now report on vaccine efficacy in the Malawi cohort of children who were followed into the second year of life . A total of 1773 healthy infants were enrolled in Blantyre , Malawi into three groups . Two groups received three doses of RIX4414 or placebo at age 6 , 10 , and 14 weeks and the third group received placebo at 6 weeks and RIX4414 at age 10 and 14 weeks . Subjects were followed by weekly home visits for episodes of gastroenteritis until 1 year of age , and were then re-consented for further follow-up to 18 - 24 months of age . Severity of gastroenteritis episodes was grade d according to the Vesikari scoring system . Seroconversion for anti-rotavirus IgA was determined on a subset of children by using ELISA on pre- and post-vaccine blood sample s. Rotavirus VP7 ( G ) and VP4 ( P ) genotypes were determined by RT-PCR . A total of 70/1030 ( 6.8 % , 95 % CI 5.3 - 8.5 ) subjects in the pooled ( 2 dose plus 3 dose ) RIX4414 group compared with 53/483 ( 11.0 % , 8.3 - 14.1 ) subjects in the placebo group developed severe rotavirus gastroenteritis in the entire follow-up period ( vaccine efficacy 38.1 % ( 9.8 - 57.3 ) ) . The point estimate of efficacy in the second year of life ( 17.6 % ; -59.2 to 56.0 ) was lower than in the first year of life ( 49.4 % ; 19.2 - 68.3 ) . There were non-significant trends towards a higher efficacy in the second year of life among children who received the three-dose schedule compared with the two-dose schedule , and a higher anti-rotavirus IgA seroresponse rate in the three-dose RIX4414 group . Rotavirus strains detected included genotype G12 ( 31 % ) ; G9 ( 23 % ) ; and G8 ( 18 % ) ; only 18 % of strains belonged to the G1P[8 ] genotype . While the optimal dosing schedule of RIX4414 in African infants requires further investigation , vaccination with RIX4414 significantly reduced the incidence of severe gastroenteritis caused by diverse rotavirus strains in an impoverished African population with high rotavirus disease burden in the first two years of life 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 c and i date 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 BACKGROUND We evaluated the immunogenicity of the pentavalent rotavirus vaccine ( PRV ) in two GAVI-eligible Asian countries , Bangladesh and Vietnam , nested in a larger r and omized , double-blind , placebo-controlled efficacy trial conducted over a two-year period from 2007 through 2009 . METHODS 2036 infants were r and omly assigned , in a 1:1 ratio , to receive three oral doses of PRV or placebo approximately at 6 , 10 , and 14 weeks of age . Concomitant use of EPI vaccines , including oral poliovirus vaccine ( OPV ) and diphtheria-tetanus-whole cell pertussis ( DTwP ) vaccine , was encouraged in accordance to the local EPI schedule . A total of 303 infants were evaluated for immunogenicity and blood sample s were collected before the first dose ( pD1 ) and approximately 14 days following the third dose ( PD3 ) . The seroresponse rates ( ≥3-fold rise from pD1 to PD3 ) and geometric mean titers ( GMTs ) were measured for anti-rotavirus immunoglobulin A ( IgA ) and serum neutralizing antibody ( SNA ) to human rotavirus serotypes G1 , G2 , G3 , G4 , and P1A[8 ] , respectively . RESULTS Nearly 88 % of the subjects showed a ≥3-fold increase in serum anti-rotavirus IgA response in the analysis of the two countries combined . When analyzed separately , the IgA response was lower in Bangladeshi children ( 78.1 % [ 95 % CI : 66.0 , 87.5 ] ) than in Vietnamese children ( 97.0 % [ 95 % CI : 89.6 , 99.6 ] ) , with a PD3 GMT of 29.1 ( units/mL ) and 158.5 ( units/mL ) , respectively . In the combined population , the SNA responses to the individual serotypes tested ranged from 10 ( G3 ) to 50 ( G1 ) percentage points lower than the responses shown in the developed countries . However , the SNA response to G3 in Vietnamese subjects was 37.3 % ( 95 % CI : 25.8 , 50.0 ) , which was similar to the G3 response rate in developed countries . CONCLUSIONS Three oral doses of PRV were immunogenic in two GAVI-eligible Asian countries : Bangladesh and Vietnam . The GMTs of both the serum anti-rotavirus IgA and SNA responses were generally higher in Vietnamese than in Bangladeshi children . The SNA responses varied by individual serotypes and were lower than the results from developed countries . The clinical significance of these observations is not understood because an immune correlate of protection has not been established BACKGROUND Rotavirus infections cause approximately 122,000 deaths among Indian children annually . METHODS The neonatal rotavirus c and i date vaccine 116E was tested in a double-blind , placebo-controlled dose-escalation trial in India . Two doses of the Vero cell-adapted vaccine were evaluated . One hundred eighty-seven infants received a vaccine dose of  1 X 10(4 ) focus-forming units  ( ffu ) and 182 received a dose of 1 X 10(5 ) ffu in a 1:1 r and omization with placebo recipients . Infants received the vaccine at 8 , 12 , and 16 weeks , separately from routine vaccines . RESULTS No significant differences in clinical adverse events or laboratory toxicity were observed between vaccine and placebo recipients . There were no vaccine-related serious adverse events . A 4-fold increase in rotavirus immunoglobulin A titer was observed in 66.7 % and 64.5 % of infants after the first administration and in 62.1 % and 89.7 % of infants after 3 administrations of doses of 1 X 10(4 ) ffu and 1 X 10(5 ) ffu , respectively ; the differences between these groups and placebo recipients were statistically significant . CONCLUSIONS Three administrations of vaccine doses of 1 X 10(4 ) ffu and 1 X 10(5 ) ffu were safe . The 1 X 10(5)-ffu dose of 116E demonstrated a robust immune response after 3 administrations . These favorable results warrant further development of the vaccine c and i date and provide optimism that vaccinating infants in the developing world will prevent serious sequelae of rotavirus infection . Clinical trials registration . NCT00439660 and IS RCT N57452882 The lyophilized formulation of a human rotavirus vaccine , Rotarix ™ ( RIX4414 ) is highly immunogenic . In order to comply with the World Health Organization 's ( WHO ) recommendation , a liquid formulation of the vaccine that does not require reconstitution was developed . The immunogenicity , reactogenicity and safety of the liquid formulation were compared with lyophilized formulation in two Finnish studies . In Study A infants aged 6 - 12 weeks received two doses of the lyophilized or liquid formulation of the vaccine or placebo following a 0,1 month schedule . In Study B , infants aged 10 - 17 weeks received two doses of either liquid or lyophilized formulation of the vaccine . In both studies , anti-rotavirus IgA antibodies were assessed pre-vaccination and one month post-Dose 2 . In Study A , the anti-rotavirus seroconversion rate was 90 % ( 95 % CI : 81.2 - 95.6 % ) and 83.7 % ( 95 % CI : 74.2 - 90.8 % ) in the groups that received the liquid and the lyophilized formulation of RIX4414 , respectively ; the respective anti-rotavirus IgA seroconversion rates in Study B were 88.6 % ( 95 % CI : 86.1 - 90.8 % ) and 90.5 % ( 95 % CI : 86.2 - 93.8 % ) . Reactogenicity and safety profiles of the two vaccine formulations were similar . Liquid formulation of the rotavirus vaccine allows greater flexibility in supply and reduces logistical costs BACKGROUND We aim ed to assess the efficacy of the oral live attenuated human rotavirus vaccine Rotarix ( RIX4414 ) for prevention of rotavirus gastroenteritis in European infants during their first 2 years of life . METHODS 3994 study participants were enrolled from six countries and were r and omly assigned two oral doses of either RIX4414 ( n=2646 ) or placebo ( n=1348 ) , which were coadministered with the first two doses of specific childhood vaccinations . Follow-up for gastroenteritis episodes was undertaken from 2 weeks post-dose two through the two consecutive rotavirus seasons following vaccinations ( combined efficacy follow-up period ; mean duration 17 months [ SD 1.6 ] ) . Our primary endpoint was vaccine efficacy against rotavirus gastroenteritis of any severity during the first efficacy follow-up period ( 2 weeks post-dose two to the end of the first rotavirus season ) . Stool specimens obtained during gastroenteritis episodes were tested for rotavirus by ELISA and typed by RT-PCR . Episodes scoring 11 or greater on the 20-point Vesikari scale were classified as severe . Analysis was according to protocol . This study is registered with Clinical Trials.gov , number NCT00140686 ( eTrack102247 ) . FINDINGS 120 infants were excluded from the according-to- protocol analysis . During the first efficacy follow-up period ( mean duration 5.7 months [ SD 1.2 ] ) , 24 of 2572 infants allocated RIX4414 versus 94 of 1302 given placebo had rotavirus gastroenteritis episodes of any severity , result ing in a vaccine efficacy of 87.1 % ( 95 % CI 79.6 - 92.1 ; p<0.0001 ) . For the combined efficacy follow-up period , vaccine efficacy against severe rotavirus gastroenteritis was 90.4 % ( 85.1 - 94.1 ; p<0.0001 ) , for admission owing to rotavirus gastroenteritis 96.0 % ( 83.8 - 99.5 ; p<0.0001 ) , and for rotavirus-related medical attention 83.8 % ( 76.8 - 88.9 ; p<0.0001 ) , and significant protection against severe rotavirus gastroenteritis by circulating G1 , G2 , G3 , G4 , and G9 rotavirus types was shown . INTERPRETATION In a European setting , two doses of RIX4414 coadministered with childhood vaccines provided high protection against any and severe rotavirus gastroenteritis , with an overall reduction of admissions for gastroenteritis over two consecutive rotavirus epidemic seasons BACKGROUND / PURPOSE Rotavirus infection is the most common etiology of acute gastroenteritis in young children worldwide . The first rotavirus vaccine was licensed by the United States Food and Drug Administration in 1998 but was suspended soon after in 1999 because of the possibility of induced intussusception . This study evaluated the safety and immunogenicity of a newly developed pentavalent rotavirus vaccine in Taiwanese children . METHODS This was a phase III global trial design ed to evaluate the safety and immunogenicity of an oral , live pentavalent rotavirus vaccine ( RotaTeq ) .  Taiwan was the only site in Asia enrolled in this trial . Normal healthy infants aged 6 - 12 weeks were enrolled , and each of the subjects received either three oral doses of the vaccine or placebo solution . The safety of the vaccine , particularly the risk of intussusception , and immunogenicity were studied . RESULTS A total of 189 infants were enrolled . No increased risk of intussusception or other adverse reactions were noted following the vaccination . RotaTeq was immunogenic among subjects enrolled in Taiwan . At least a three-fold rise in serum antirotavirus IgA antibody was found among 93 % of the vaccine group . The immunogenicity of RotaTeq in Taiwan was comparable to that in other areas . CONCLUSION The pentavalent human-bovine vaccine , RotaTeq , was safe , generally well-tolerated , and immunogenic among Taiwanese infants 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 In a large placebo-controlled efficacy trial of the  rhesus tetravalent ( RRV-TV ) and serotype 1 monovalent ( RRV-S1 ) rotavirus vaccines in multiple sites throughout the United States , protection against rotavirus disease over a 2-year period was found to be 57 and 40 % , respectively ( Bernstein et al. , J. Am . Med . Assoc . , 1995 , 273 , 1191 - 1196 ) . Sera collected from a subset of subjects during this trial were used to determine possible correlations between rotavirus antibody responses after vaccination and protection . Between 82 % ( RRV-S1 ) and 92 % ( RRV-TV ) of the vaccinees seroconverted by at least one of the six antibody assays performed ( i.e. rotavirus IgA and neutralizing antibody to RRV and serotype 1 - 4 human rotaviruses ) . Rises in neutralizing antibody were due primarily to RRV . The seroconversion rate was only 18 - 22 % to each of the four human rotavirus serotypes following RRV-TV vaccination and was only 43 % to serotype 1 human rotavirus after RRV-S1 administration . Furthermore , no correlate of immunity against rotavirus infection or disease was identifiable based on seroconversion to any of the antibodies measured . Likewise , no consistent relationship was found between the titers of any of these six antibodies following vaccination and protection against rotavirus , thus suggesting that serum antibody titers will not be useful markers of protection with these reassortant RRV vaccines . In addition , vaccinated subjects did not develop higher titers of neutralizing antibody to human rotaviruses following a subsequent natural rotavirus illness , a further indication that only weak immune responses to human rotaviruses were stimulated by vaccination with the RRV reassortants . ( ABSTRACT TRUNCATED AT 250 WORDS This study assessed the immunogenicity and safety of a human rotavirus vaccine RIX4414 ; the effect of co-administration of childhood vaccines on the immune responses was also assessed . Healthy infants aged 6 - 14 weeks received two doses of  RIX4414/placebo concomitantly with the primary childhood vaccination ( Infanrix hexa , Infanrix quinta , Meningitec and /or Prevnar ) , respecting the vaccination schedule of each country . Anti-rotavirus IgA seroconversion rate ( ELISA cut-off 20 U/ml ) was measured pre-vaccination and 1 - 2 months post-Dose 2 . Immune response against diphtheria , tetanus , pertussis , hepatitis B , Haemophilus influenzae type b , inactivated polio virus , pneumococcal polysaccharide conjugate ( France and Germany ) and meningococcal group C conjugate vaccines ( Spain ) were measured approximately 1-month post-Dose 3 . An overall anti-rotavirus IgA seroconversion rate of 86.5%(95 % CI : 83.9 - 88.8 ) was observed in the RIX4414 group 1-month post-Dose 2 . The seroconversion rate in Finl and and Italy ( 3 and 5-month schedule ) was 94.6%(95 % CI : 90.0 - 97.5 ) and 92.3%(95 % CI : 64.0 - 99.8 ) , respectively . Immune response to the childhood vaccines was unaffected following co-administration with RIX4414 . Reactogenicity profile was similar for RIX4414 and placebo groups . RIX4414 was immunogenic and well tolerated in European infants and the co-administration of routine childhood vaccines with RIX4414 did not negatively impact the immune responses to these vaccines The oral , pentavalent rotavirus vaccine ( PRV ) , RotaTeq was assessed for prevention of severe rotavirus gastroenteritis ( RVGE ) in young children in two multi-site , r and omized , placebo-controlled field trials ; one in Asia ( Vietnam and Bangladesh ) and the other in sub-Saharan Africa ( Ghana , Kenya and Mali ) . The efficacy results for the Mali site of the multi-country trial are presented here . We r and omly assigned infants in a 1:1 ratio to receive 3 doses of  PRV/placebo  at approximately 6 , 10 , and 14 weeks of age . Gastroenteritis episodes were captured passively at the local health centers and by home visits . The primary study outcome was severe RVGE , as defined by a score of ≥ 11 using the Vesikari Clinical Scoring System occurring ≥ 14 days after the third dose until the end of the study . Other efficacy analyses included efficacy against severe RVGE through the first year and during the second years of life , as well as efficacy after receiving at least one dose of vaccine . In total , 1960 infants were enrolled in the trial at the Mali site and sera were collected on a subset of infants ( approximately 150 ) for immunogenicity testing . In the first year of follow-up , largely due to cultural practice s to visit traditional healers as the first point of care , the point estimate of efficacy was unreliable : the per protocol vaccine efficacy against severe RVGE was 1 % ( 95 % confidence interval [ CI ] : -431.7 , 81.6 ) ; the intention-to-treat vaccine efficacy was 42.9 % ( 95 % CI : -125.7 , 87.7 ) . During the second year of follow-up , after the surveillance system was modified to adapt to local customs and health care seeking practice s , the point estimate of per- protocol vaccine efficacy was 19.2 % ( 95 % CI : -23.1,47.3 % ) . 82.5 % of Malian infants ( 95 % CI : 70.1,91.3 % ) who received PRV mounted a seroresponse ( ≥ 3-fold rise from baseline ( prevaccination ) to post-dose 3 vaccination ) of anti-rotavirus immunoglobulin A antibody , with a post third-dose geometric mean titer ( GMT ) of 31.3 units/mL. By contrast , only 20.0 % of placebo recipients ( 95 % CI : 10.0 , 33.7 % ) developed a seroresponse and the post-third dose GMT was 3.2 units/mL. None of the serious clinical adverse events observed were considered to be vaccine-related BACKGROUND Rotavirus is a leading cause of childhood gastroenteritis and death worldwide . METHODS We studied healthy infants approximately 6 to 12 weeks old who were r and omly assigned to receive three oral doses of  live pentavalent human-bovine ( WC3 strain ) reassortant rotavirus vaccine containing human serotypes G1 , G2 , G3 , G4 , and P[8 ] or placebo at 4-to-10-week intervals in a blinded fashion . Active surveillance was used to identify subjects with serious adverse and other events . RESULTS The 34,035 infants in the vaccine group and 34,003 in the placebo group were monitored for serious adverse events . Intussusception occurred in 12 vaccine recipients and 15 placebo recipients within one year after the first dose including six vaccine recipients and five placebo recipients within 42 days after any dose ( relative risk , 1.6 ; 95 percent confidence interval , 0.4 to 6.4 ) . The vaccine reduced hospitalizations and emergency department visits related to G1-G4 rotavirus gastroenteritis occurring 14 or more days after the third dose by 94.5 percent ( 95 percent confidence interval , 91.2 to 96.6 percent ) . In a nested sub study , efficacy against any G1-G4 rotavirus gastroenteritis through the first full rotavirus season after vaccination was 74.0 percent ( 95 percent confidence interval , 66.8 to 79.9 percent ) ; efficacy against severe gastroenteritis was 98.0 percent ( 95 percent confidence interval , 88.3 to 100 percent ) . The vaccine reduced clinic visits for G1-G4 rotavirus gastroenteritis by 86.0 percent ( 95 percent confidence interval , 73.9 to 92.5 percent ) . CONCLUSIONS This vaccine was efficacious in preventing rotavirus gastroenteritis , decreasing severe disease and health care contacts . The risk of intussusception was similar in vaccine and placebo recipients . ( Clinical Trials.gov number , NCT00090233 . BACKGROUND Rotavirus vaccine has proved effective for prevention of severe rotavirus gastroenteritis in infants in developed countries , but no efficacy studies have been done in developing countries in Asia . We assessed the clinical efficacy of live oral pentavalent rotavirus vaccine for prevention of severe rotavirus gastroenteritis in infants in Bangladesh and Vietnam . METHODS In this multicentre , double-blind , placebo-controlled trial , undertaken in rural Matlab , Bangladesh , and urban and periurban Nha Trang , Vietnam , infants aged 4 - 12 weeks without symptoms of gastrointestinal disorders were r and omly assigned ( 1:1 ) to receive three oral doses of pentavalent rotavirus vaccine 2 mL or placebo at around 6 weeks , 10 weeks , and 14 weeks of age , in conjunction with routine infant vaccines including oral poliovirus vaccine . R and omisation was done by computer-generated r and omisation sequence in blocks of six . Episodes of gastroenteritis in infants who presented to study medical facilities were reported by clinical staff and from parent re collection . The primary endpoint was severe rotavirus gastroenteritis ( Vesikari score > or=11 ) arising 14 days or more after the third dose of placebo or vaccine to end of study ( March 31 , 2009 ; around 21 months of age ) . Analysis was per protocol ; infants who received scheduled doses of vaccine or placebo without intervening laboratory-confirmed naturally occurring rotavirus disease earlier than 14 days after the third dose and had complete clinical and laboratory results were included in the analysis . This study is registered with Clinical Trials.gov , number NCT00362648 . FINDINGS 2036 infants were r and omly assigned to receive pentavalent rotavirus vaccine ( n=1018 ) or placebo ( n=1018 ) . 991 infants assigned to pentavalent rotavirus vaccine and 978 assigned to placebo were included in the per- protocol analysis . Median follow up from 14 days after the third dose of placebo or vaccine until final disposition was 498 days ( IQR 480 - 575 ) . 38 cases of severe rotavirus gastroenteritis ( Vesikari score > or=11 ) were reported during more than 1197 person-years of follow up in the vaccine group , compared with 71 cases in more than 1156 person years in the placebo group , result ing in a vaccine efficacy of 48.3 % ( 95 % CI 22.3 - 66.1 ) against severe disease ( p=0.0005 for efficacy > 0 % ) during nearly 2 years of follow-up . 25 ( 2.5 % ) of 1017 infants assigned to receive vaccine and 20 ( 2.0 % ) of 1018 assigned to receive placebo had a serious adverse event within 14 days of any dose . The most frequent serious adverse event was pneumonia ( vaccine 12 [ 1.2 % ] ; placebo 15 [ 1.5 % ] ) . INTERPRETATION In infants in developing countries in Asia , pentavalent rotavirus vaccine is safe and efficacious against severe rotavirus gastroenteritis , and our results support exp and ed WHO recommendations to promote its global use . FUNDING PATH ( GAVI Alliance grant ) and Merck BACKGROUND Human rotavirus vaccine ( HRV ; i.e. , Rotarix ) reduced the incidence of severe rotavirus gastroenteritis ( RVGE ) by 77 % ( 95 % Confidence interval : 56 - 88 % ) during the first year of life in South Africa . Persistence of HRV-derived protection against RVGE during subsequent rotavirus seasons , although evident in industrialized setting s , remains to be established in African setting s. This study reports on the efficacy of HRV against severe RVGE over two consecutive rotavirus seasons in South African children . METHODS A prospect i ve , double-blind , placebo controlled multi-centered trial in South Africa and Malawi r and omly assigned infants in a 1:1:1 ratio to receive either two ( 10 and 14 weeks ; HRV_2D ) or three ( 6 , 10 and 14 weeks ; HRV_3D ) doses of HRV or placebo . The primary analysis involved pooling of HRV_2D and HRV_3D arms . Episodes of gastroenteritis caused by wild-type rotavirus were identified through active follow-up surveillance and grade d by the Vesikari scale . RESULTS 1339 infants ( 447 in the HRV_2D group , 447 in the HRV_3D group and 445 in the placebo group ) were enrolled in Year 2 of the study , including 1035 ( 77.3 % ) who were followed up over two consecutive rotavirus seasons ( i.e. , Cohort 2 subjects ) . Rotarix was associated with ongoing protection against severe RVGE , preventing 2.5 episodes per 100 vaccinated children over two consecutive rotavirus seasons ; vaccine efficacy : 59 % ( 95 % Confidence interval : 1 - 83 % ) . An exploratory analysis indicated better immunogenicity ( among Cohort 1 subjects ) and a higher point-efficacy estimate over two seasons in the HRV_3D compared to HRV_2D arms of the study in Cohort 2 subjects . CONCLUSION Rotarix is associated with significant reductions in severe gastroenteritis episodes through 2 years of life among South African children . Further research is needed to determine the optimal dosing schedule of Rotarix in providing long-term protection against rotavirus illness in African children Background : High rates of typhoid fever and the emergence of multi-drug resistant strains create a need for prevention efforts including vaccines . Socio-behavioral research can provide important data for participation in future trials and public health vaccination campaigns . Design : A 3b phase clinical trial in Kolkata India including pre- and post-vaccination socio-behavioral surveys . Methods : 700 households r and omly selected 503 respondents ( 71.85 % ) completing both the pre- and post- closed-ended surveys .  Data analysis included descriptive statistics , Pearson ’s chi-square tests , independent t-tests , and stepwise logistic regression analysis . Four open-ended questions were included in the survey . These qualitative data were coded and review ed for common themes and patterns . Results : 47.9 % of respondents were male . Ward 29 respondents included 32.4 % Hindu and Ward 30 respondents were 99.0 % Hindu . Lower rates of participation were found among Muslim respondents and those with post high school education . Lack of information and negative information affected participation . Joint decision-making within households increased participation rates . Conclusions : Individuals ’ decisions to participate or not participate in a vaccine trial entail a balance between individual beliefs , household dynamics , and socio-political influences . Efforts prior to vaccination trials need to develop strategies which address potential underlying mediators for belief systems as well as structural factors which may reinforce individuals ’ beliefs and perceptions about vaccination trials BACKGROUND Efficacy of the pentavalent rotavirus vaccine ( PRV ) , RotaTeq ( ® ) , against  severe rotavirus gastroenteritis ( RVGE )  was evaluated in two double-blind , placebo-controlled , multicenter Phase III clinical trials conducted in GAVI-eligible countries in Africa ( Ghana , Kenya , and Mali ) and in Asia ( Bangladesh and Vietnam ) from March 2007 through March 2009 . The findings from each continent have been analyzed and presented separately , according to a single identical protocol . Ad hoc analyses combining data from the five sites were performed to further assess the impact of PRV . METHODS 6674 infants ( 4705 infants from Africa and 1969 infants from Asia ) , r and omized 1:1 to receive 3 doses of PRV/placebo at approximately 6- , 10- , and 14-weeks of age according to each country 's EPI schedule , were included in the per protocol efficacy analysis . Breastfeeding and concomitant administration of EPI vaccines , including OPV , were allowed . Episodes of gastroenteritis ( GE ) in infants who presented to study facilities were captured and scored using the 20-point Vesikari scale . Stool sample s were analyzed by rotavirus-specific EIA to detect presence of rotavirus antigen and RT-PCR to determine the G/P genotypes . We assessed efficacy to prevent all-cause GE and RVGE at a variety of cut-off points ( score≥11 , severe ; score≥15 , very severe ) . RESULTS Vaccine efficacy ( VE ) against RVGE , regardless of serotype , through the entire follow-up period for any severity , severe ( score≥11 ) , and very severe ( score≥15 ) was 33.9 % , 95 % CI ( 22.7 , 43.5 ) , 42.5 % , 95 % CI ( 27.4 , 54.6 ) , and 51.2 % , 95 % CI ( 26.3 , 68.2 ) , respectively . Through the first year of life , VE against severe RVGE was 58.9 % , 95 % CI ( 40.0 , 72.3 ) and against all-cause severe GE was 23.0 % , 95 % CI ( 5.4 , 37.3 ) . VE against severe RVGE caused by non-vaccine G serotypes , G8 and G9 , through the entire follow-up period was 87.5 % , 95 % CI ( 6.8 , 99.7 ) and 48.0 % , 95 % CI ( -5.5 , 75.6 ) , respectively . All G8 strains were associated with P2A[6 ] ( a P-type not contained in PRV ) , while the majority of the G9 strains were associated with P1A[8 ] ( a P-type contained in PRV ) . CONCLUSIONS Combining data from the 5 sites strengthens the precision of VE estimates and reveals rising VE with increased RVGE severity . Extrapolating data from VE against severe GE and RVGE suggest that 39 % of severe GE episodes during the first year of life were due to rotavirus , highlighting substantial , potentially preventable , public health burden of RVGE . PRV provides protection against non-vaccine serotypes ( G8P2A[6 ] ) BACKGROUND Peak incidence of rotavirus gastroenteritis is seen in infants between 6 and 24 months of age . We therefore aim ed to assess the 2-year efficacy and safety of an oral live attenuated human rotavirus vaccine for prevention of severe gastroenteritis in infants . METHODS 15 183 healthy infants aged 6 - 13 weeks from ten Latin American countries r and omly assigned in a 1 to 1 ratio to receive two oral doses of RIX4414 or placebo at about 2 and 4 months of age in a double-blind , placebo-controlled phase III study were followed up until about 2 years of age . Primary endpoint was vaccine efficacy from 2 weeks after dose two until 1 year of age . Treatment allocation was concealed from investigators and parents of participating infants . Efficacy follow-up for gastroenteritis episodes was undertaken from 2 weeks after dose two until about 2 years of age . Analysis was according to protocol . This study is registered with Clinical Trials.gov , number NCT00140673 ( eTrack444563 - 023 ) . FINDINGS 897 infants were excluded from the according-to- protocol analysis . Fewer cases ( p<0.0001 ) of severe rotavirus gastroenteritis were recorded for the combined 2-year period in the RIX4414 group ( 32 [ 0.4 % ] of 7205 ; 95 % CI 0.3 - 0.6 ) than in the placebo group ( 161 [ 2.3 % ] of 7081 ; 1.9 - 2.6 ) , result ing in a vaccine efficacy of 80.5 % ( 71.3 - 87.1 ) to 82.1 % ( 64.6 - 91.9 ) against wild-type G1 , 77.5 % ( 64.7 - 86.2 ) against pooled non-G1 strains , and 80.5 % ( 67.9 - 88.8 ) against pooled non-G1 P[8 ] strains . Vaccine efficacy for hospital admission for rotavirus gastroenteritis was 83.0 % ( 73.1 - 89.7 ) and for admission for diarrhoea of any cause was 39.3 % ( 29.1 - 48.1 ) . No cases of intussusception were reported during the second year of follow-up . INTERPRETATION Two doses of RIX4414 were effective against severe rotavirus gastroenteritis during the first 2 years of life in a Latin American setting . Inclusion of RIX4414 in routine paediatric immunisations should reduce the burden of rotavirus gastroenteritis worldwide We recently completed a double-blind , placebo-controlled , multicenter Phase III clinical trial of the pentavalent rotavirus vaccine ( PRV ) in three African countries , Ghana , Kenya , and Mali , from April 2007 to March 2009 . The immunogenicity of PRV  in African infants is described . In total , 5468 infants were r and omized 1:1 to receive 3 doses of PRV or placebo at approximately 6 , 10 , and 14 weeks of age . Breastfeeding and concomitant administration of EPI vaccines , including OPV , were allowed , and HIV-infected infants were not excluded . Immunogenicity of PRV was assessed by measuring serum anti-rotavirus IgA responses , as well as serum neutralization antibody ( SNA ) to the human rotavirus serotypes G1 , G2 , G3 , G4 and P1A[8 ] in approximately 150 infants per country . Sera were collected pre-dose 1 ( pD1 ) and approximately 14 days post-dose 3 ( PD3 ) for immunological analysis . For the sero-response rates ( ≥ 3-fold rise from pD1 to PD3 ) , the number of subjects evaluable included those with both pD1 and PD3 data available . PRV was immunogenic in African children and significantly reduced severe RVGE in African children through the first two years of life . The pooled anti-rotavirus IgA sero-response rate was 78.3 % , with consistent rates in each of the African sites : 73.8 % ( Kenya ) , 78.9 % ( Ghana ) , and 82.5 % ( Mali ) ; but generally lower than that reported in Europe and USA . PD3 GMTs ( 28.2 dilution-units ) were 5 - 10 times lower than those assessed in subjects in clinical trials in developed countries . SNA responses to human rotavirus serotypes G1-G4 and P1A[8 ] ranged from 6.3 % ( G3 ) to 26.5 % ( G4 ) . PD3 SNA GMTs to G1 and P1A[8 ] were 4-fold and 3-fold lower respectively , when compared to the corresponding GMTs in subjects who received PRV in similar studies conducted in developed countries . PRV was immunogenic in African infants , and the anti-rotavirus IgA sero-response rates were similar across all three African sites although lower than those observed in Europe and USA . While immune correlates of protection have not been established for rotavirus , the findings are consistent with lower efficacy rates demonstrated during this trial . Further investigation is needed to underst and the reason for the lower immunogenicity observed Evaluation of immunogenicity and safety of a 2-dose liquid formulation of human rotavirus vaccine , RIX4414 following WHO 's Exp and ed Program on Immunization ( EPI ) schedule ( 0 , 1 , and 2 months ; Month 0 indicates day of enrollment ) in Vietnam and the Philippines . Infants aged 6 - 10 ( mean=8.7 ± 1.07 weeks Vietnam ) and 5 - 10 weeks ( mean=6.6 ± 1.03 weeks Philippines ) received two doses of RIX4414 vaccine ( V ) and one dose of placebo ( PL ) or three placebo doses concomitantly with commercially available diphtheria-tetanus-whole-cell pertussis , hepatitis B and oral poliovirus vaccines . The vaccination schedules were : V-V-PL , V-PL-V and PL-PL-PL ( Vietnam ) ; PL-V-V , V-PL-V and PL-PL-PL ( Philippines ) . Anti-rotavirus seroconversion rate was assessed pre-vaccination and post-vaccination ( ELISA cut-off=20 U/ml ) . 375 infants were enrolled in each country . Seroconversion rates at one month post-Dose 2 of RIX4414 were Vietnam 63.3 % ( 95 % CI : 54.3 - 71.6 ) in V-V-PL group and 81.5 % ( 95 % CI : 73.4 - 88 ) in V-PL-V group ; Philippines 70 % ( 95 % CI : 61 - 78 ) in PL-V-V group and 59.2 % ( 95 % CI : 49.8 - 68 ) in V-PL-V group . Frequencies of solicited ( 8-day post-each dose ) and unsolicited symptoms ( 31-day post-each dose ) were similar . Two-doses of rotavirus vaccine administered within the WHO EPI offer flexibility in existing schedule , though both schedules provides good immune responses Objectives : The live oral pentavalent rotavirus vaccine ( PRV ) is well tolerated and highly efficacious against rotavirus gastroenteritis . This open-label , multicenter study evaluated the immunogenicity and safety of coadministering oral poliovirus vaccine ( OPV ) with PRV . Methods : From 2005 to 2006 , healthy 6- to 12-week-old Latin American infants were r and omized to PRV and OPV concomitantly or PRV 2–4 weeks before OPV . Three doses of each vaccine were administered 8–10 weeks apart . Subjects did not receive OPV at birth . Routine licensed pediatric vaccines were allowed . Antibody responses to PRV and OPV were evaluated 42 days after the last dose of each vaccine . Adverse events were recorded for 14 days after each study visit . Results : In the concomitant-use group ( n = 372 ) , more than 98 % of subjects achieved serum-neutralizing antibody titer ≥1:8 against poliovirus types 1 , 2 , and 3 . The poliovirus seroprotection rate in the concomitant-use group was statistically noninferior to the staggered-use group ( n = 363 ) . The immunoglobulin A ( IgA ) antirotavirus geometric mean titer was 46 % lower in the concomitant-use group than in the staggered-use group . However , concomitant use elicited a ≥3-fold increase ( from predose 1 to postdose 3 ) in serum antirotavirus IgA in 93 % of subjects and achieved the definition of noninferiority . Both regimens were similarly well tolerated . Conclusions : PRV did not interfere with immune responses to OPV . Although coadministration with OPV reduced serum antirotavirus IgA geometric mean titer , seroresponse rates were high and consistent with those observed in previous studies showing high vaccine efficacy . These results support including PRV in vaccination schedules involving OPV BACKGROUND Rotavirus gastroenteritis causes many deaths in infants in sub-Saharan Africa . Because rotavirus vaccines have proven effective in developed countries but had not been tested in developing countries , we assessed efficacy of a pentavalent rotavirus vaccine against severe disease in Ghana , Kenya , and Mali between April , 2007 , and March , 2009 . METHODS In our multicentre , double-blind , placebo-controlled trial , undertaken in rural areas of Ghana and Kenya and an urban area of Mali , we r and omly assigned infants aged 4 - 12 weeks without symptoms of gastrointestinal disorders in a 1:1 ratio to receive three oral doses of pentavalent rotavirus vaccine 2 mL or placebo at around 6 weeks , 10 weeks , and 14 weeks of age . Infants with HIV infection were not excluded . R and omisation was done by computer-generated r and omisation sequence in blocks of six . We obtained data for gastrointestinal symptoms from parents on presentation to health-care facilities and clinical data were obtained prospect ively by clinicians . The primary endpoint was severe rotavirus gastroenteritis ( Vesikari score > or=11 ) , detected by enzyme immunoassay , arising 14 days or more after the third dose of placebo or vaccine to end of study ( March 31 , 2009 ; around 21 months of age ) . Analysis was per protocol ; infants who received scheduled doses of vaccine or placebo without intervening laboratory-confirmed naturally occurring rotavirus disease earlier than 14 days after the third dose and had complete clinical and laboratory results were included in the analysis . This study is registered with Clinical Trials.gov , number NCT00362648 . FINDINGS 5468 infants were r and omly assigned to receive pentavalent rotavirus vaccine ( n=2733 ) or placebo ( n=2735 ) . 2357 infants assigned to vaccine and 2348 assigned to placebo were included in the per- protocol analysis . 79 cases of severe rotavirus gastroenteritis were reported in 2610.6 person-years in the vaccine group , compared with 129 cases in 2585.9 person-years in the placebo group , result ing in a vaccine efficacy against severe rotavirus gastroenteritis of 39.3 % ( 95 % CI 19.1 - 54.7 , p=0.0003 for efficacy > 0 % ) . Median follow-up in both groups was 527 days starting 14 days after the third dose of vaccine or placebo was given . 42 ( 1.5 % ) of 2723 infants assigned to receive vaccine and 45 ( 1.7 % ) of 2724 infants assigned to receive placebo had a serious adverse event within 14 days of any dose . The most frequent serious adverse event was gastroenteritis ( vaccine 17 [ 0.6 % ] ; placebo 17 [ 0.6 % ] ) . INTERPRETATION Pentavalent rotavirus vaccine is effective against severe rotavirus gastroenteritis in the first 2 years of life in African countries with high mortality in infants younger than 5 years . We support WHO 's recommendation for adoption of rotavirus vaccine into national exp and ed programmes on immunisation in Africa . FUNDING PATH ( GAVI Alliance grant ) and Merck This study evaluates the safety and efficacy against severe rotavirus gastroenteritis of the oral live attenuated human rotavirus vaccine RIX4414 ( Rotarix )  during the first 2 years of life in Asian infants from high-income countries . Healthy infants were enrolled to receive 2 doses of RIX4414 ( N=5,359 ) or placebo ( N=5,349 ) . From 2 weeks post-dose 2 to 2 years of age , vaccine efficacy was 96.1 % ( 95%CI:85.1 % ; 99.5 % ) against severe rotavirus gastroenteritis , 100 % ( 95%CI:80.8 % ; 100 % ) against wild-type G1P[8 ] and 93.6 % ( 95%CI:74.7 % ; 99.3 % ) against circulating non-G1 rotavirus types . No intussusception cases were reported within 31 days post-vaccination . RIX4414 shows a good safety profile and offers high protection during the first 2 years of life with potentially significant public health impact in this population BACKGROUND A phase II , r and omized , double-blind , placebo-controlled study was conducted in South Africa during 2003 - 2004 to evaluate the safety , reactogenicity , and immunogenicity of 2 regimens of the live attenuated oral human rotavirus vaccine RIX4414 when coadministered with the Exp and ed Program on Immunization childhood vaccines , including oral polio vaccine . METHODS Healthy infants were r and omized ( 2:2:1 ) to receive either 2 doses of RIX4414 ( n = 190 ; at 10 and 14 weeks , with placebo at 6 weeks ) , 3 doses of RIX4414 ( n = 189 ; at 6 , 10 , and 14 weeks ) , or 3 doses of placebo ( n = 96 ) , all with concomitant routine vaccinations . The antirotavirus IgA seroconversion rate was assessed using enzyme-linked immunosorbent assay at 2 months after the last dose of RIX4414 or placebo . Antipolio types 1 , 2 , and 3 antibodies were measured using a virus neutralization assay . Solicited symptoms were recorded for 15 days after each dose . RESULTS The antirotavirus IgA seroconversion rates were similar in the RIX4414 2- and 3-dose groups ( 44.3 % and 44.4 % , respectively ; P = .544 , by 1-sided Fisher exact test ) and antirotavirus IgA geometric mean concentrations were also comparable . Seroprotection rates for antipolio types 1 , 2 , and 3 antibodies were high ( 93%-100 % ) and were not significantly different among groups . Solicited symptoms reported within 15 days after vaccination were similar in all groups . CONCLUSIONS The immune seroconversion response to the RIX4414 vaccine with 3 doses was not superior to the 2-dose regimen . There was no interference by either regimen with antibody response to oral polio vaccine , and RIX4414 was well tolerated when given with routine vaccinations
BACKGROUND Identifying an immunological correlate of protection for rotavirus vaccines ( Rotarix [ RV1 ] and RotaTeq [ RV5 ] ) would substantially facilitate testing of interventions for improving efficacy in developing countries and evaluating additional c and i date rotavirus vaccines .