Efficient tetanus toxoid immunization on vitamin D supplementation Non-specific effects of vaccination on child survival: prospective cohort study in Burkina Faso Poor immune responses to a birth dose of diphtheria, tetanus, and acellular pertussis vaccine. Effects of supplementation with tocotrienol-rich fraction on immune response to tetanus toxoid immunization in normal healthy volunteers Delaying BCG vaccination from birth to 10 weeks of age may result in an enhanced memory CD4 T cell response. Delayed hypersensitivity to tuberculin, total immunoglobulin E, specific sensitization, and atopic manifestation in longitudinally followed early Bacille Calmette-Guérin-vaccinated and nonvaccinated children. Delaying Bacillus Calmette-Guérin Vaccination from Birth to 4 1/2 Months of Age Reduces Postvaccination Th1 and IL-17 Responses but Leads to Comparable Mycobacterial Responses at 9 Months of Age Antigen-Specific Responses to Diphtheria-Tetanus-Acellular Pertussis Vaccine in Human Infants Are Initially Th2 Polarized Specific immune response in adult medical personnel immunized with acellular pertussis vaccine with special emphasis on T helper cell response. A Longitudinal Study of BCG Vaccination in Early Childhood: The Development of Innate and Adaptive Immune Responses Humoral and cell-mediated immune responses to an early 2-dose measles vaccination regimen in the United States. Proof-of-Concept, Randomized, Controlled Clinical Trial of Bacillus-Calmette-Guerin for Treatment of Long-Term Type 1 Diabetes Persistence of the immune response induced by BCG vaccination Immunogenicity of a Whole-Cell Pertussis Vaccine with Low Lipopolysaccharide Content in Infants Cell-mediated and antibody immune responses to AIK-C and Connaught monovalent measles vaccine given to 6 month old infants. Influence of Mycobacterium bovis Bacillus Calmette-Guérin on Antibody and Cytokine Responses to Human Neonatal Vaccination1 Neonatal BCG vaccination induces IL-10 production by CD4+ CD25+ T cells. Measles vaccination in the presence of maternal antibodies primes for a balanced humoral and cellular response to revaccination. Effect of BCG vaccination in asthmatic schoolchildren. Acellular pertussis vaccines containing genetically detoxified pertussis toxin induce long-lasting humoral and cellular responses in adults. Cytokine mRNA Expression and Proliferative Responses Induced by Pertussis Toxin, Filamentous Hemagglutinin, and Pertactin ofBordetella pertussis in the Peripheral Blood Mononuclear Cells of Infected and Immunized Schoolchildren and Adults The immunological effect of revaccination with Bacille Calmette-Guérin vaccine at 19 months of age. BCG-induced increase in interferon-gamma response to mycobacterial antigens and efficacy of BCG vaccination in Malawi and the UK: two randomised controlled studies Immune modulation after measles vaccination of 6-9 months old Bangladeshi infants. Treatment of recalcitrant warts with intralesional measles, mumps, and rubella vaccine: a promising approach. Influence of measles vaccination on the progression of atopic dermatitis in infants. Effect of tetanus immunization on t-helper cytokine production in adults with and without allergic rhinitis. The effect of Edmonston-Zagreb and Schwarz measles vaccines on immune response in infants. Increased Female-Male Mortality Ratio Associated With Inactivated Polio and Diphtheria-Tetanus-Pertussis Vaccines: Observations From Vaccination Trials in Guinea-Bissau The effect of at-birth vitamin A supplementation on differential leucocyte counts and in vitro cytokine production: an immunological study nested within a randomised trial in Guinea-Bissau. Influence of Bacillus Calmette-Guèrin vaccination at birth and 2 months old age on the peripheral blood T-cell subpopulations [gamma/delta and alpha-beta T cell]. Patterns and implications of naturally acquired immune responses to environmental and tuberculous mycobacterial antigens in northern Malawi. Mycobacterial Purified Protein Derivatives Stimulate Innate Immunity: Malawians Show Enhanced Tumor Necrosis Factor Alpha, Interleukin-1β (IL-1β), and IL-10 Responses Compared to Those of Adolescents in the United Kingdom Cytokine production patterns and antibody response to measles vaccine. Newborns develop a Th1-type immune response to Mycobacterium bovis bacillus Calmette-Guérin vaccination. Lymphocyte response to tetanus toxin T-cell epitopes: effects of tetanus vaccination and concurrent malaria prophylaxis. Bacille Calmette-Guérin vaccination enhances human gamma delta T cell responsiveness to mycobacteria suggestive of a memory-like phenotype. A double-blind, placebo-controlled study of Mycobacterium-specific human immune responses induced by intradermal bacille Calmette-Guérin vaccination.
Background / Objectives : Vitamin D mediates immunomodulatory functions , and its deficiency has been associated with an increased prevalence of immunological diseases . The supplementation of vitamin D might be therapeutically beneficial , for example , in lupus erythematosus patients . However , its affect on established recall immune responses is undefined . Subjects/ Methods : In all , 32 individuals were r and omized in a placebo controlled , double-blind setting , and received vitamin D ( daily 2000 IU ) for 10 weeks followed by tetanus toxoid ( TT ) booster immunization . Results : During vitamin D supplementation the median 25-hydroxyvitamin D serum concentration increased to 80.3 nM , which as expected decreased in the placebo group to 29.1 nM during the ultraviolet-deprived winter months . The TT-specific immunoglobulin G ( IgG ) boost efficiency was marginal higher in the vitamin D group ( P=0.04 ) . The increase of the 25-hydroxyvitamin D levels correlated with the increase of TT – IgG serum concentrations . The induction of specific serum IgA and specific antibody secreting cells was comparable between both groups . Accordingly , the TT-specific and polyclonally triggered T-cell cytokine profiles were stable as well . Conclusions : Vitamin D supplementation was successful and booster immunization induced efficiently specific antibodies titers Abstract Objective To study the effect of vaccination on  mortality before 2 years of age in a developing country . Design Prospect i ve cohort study . Setting Rural communities in Burkina Faso . Participants 9085 children born in the study area between 1985 and 1993 . Main outcome measure Child death rate . Results Mortality before 2 years of age was lower in children who had been vaccinated : those vaccinated with BCG only had significantly lower mortality ( risk ratio for vaccinated v unvaccinated children 0.37 , 95 % confidence interval 0.29 to 0.48 ) as did those vaccinated with diphtheria , tetanus , and pertussis only ( 0.24 , 0.13 to 0.43 ) . The second dose of diphtheria , tetanus , and pertussis was not associated with lower mortality ( 0.80 , 0.58 to 1.12 ) . Conclusion Vaccination with diphtheria , tetanus , and pertussis as well as BCG is associated with better survival of children up to 2 years of age OBJECTIVES To evaluate the safety and immunogenicity of an additional birth dose of diphtheria , tetanus , and acellular pertussis vaccine ( DTaP ) . STUDY DESIGN Fifty infants between 2 to 14 days of age were r and omly assigned to receive either DTaP and hepatitis B vaccines ( experimental ) or hepatitis B alone ( control ) at birth . At 2 , 4 , 6 , and 17 months of age , DTaP and routine vaccines were administered to both groups . Safety data were collected after each dose , and sera were obtained at birth , 6 , 7 , 17 , and 18 months . Immune responses to pertussis toxin , filamentous hemagglutinin , pertactin , and fimbriae were measured by enzyme-linked immunosorbent assay ; responses to other vaccines were assessed . RESULTS No differences were seen between the 2 groups in either local or systemic reactions ; all vaccines were well tolerated . Compared with the control group , infants in the experimental group demonstrated significantly lower geometric mean antibody concentrations for pertussis toxin and pertactin 6 , 7 , and 18 months , for fimbrae at 6 , 7 , 17 , and 18 months , and for FHA at 18 months , and lower geometric mean antibody concentrations for diphtheria at 7 months . Immune responses to all other vaccine antigens were comparable . CONCLUSION Administration of an additional dose of DTaP at birth was safe but was associated with a significantly lower response to diphtheria and 3 of 4 pertussis antigens compared with controls Background / Objectives : Vitamin E is an essential fat-soluble vitamin that has been shown to induce favorable effects on animal and human immune systems . The objective of this study was to assess the effects of tocotrienol-rich fraction ( TRF ) supplementation on immune response following tetanus toxoid ( TT ) vaccine challenge in healthy female volunteers . Subjects/ Methods : In this double-blinded , placebo-controlled clinical trial , participants were r and omly assigned to receive either placebo ( control group ) or 400 mg of TRF ( study group ) supplementation daily . Over the 2-month period of the study , volunteers were asked to attend three clinical sessions ( that is , on days 0 , 28 and 56 ) and blood sample s were obtained from the volunteers during the follow-up . On day 28 , all volunteers were also vaccinated with the TT vaccine ( 20 Lf ) intramuscularly . Results : The results from the clinical trial showed that TRF supplementation significantly increased the total vitamin E level in the plasma of the TRF-supplemented volunteers compared with the placebo group , indicating overall compliance . Volunteers supplemented with TRF showed a significantly ( P<0.05 ) enhanced production of interferon-γ and interleukin (IL)-4 by the mitogen or TT-stimulated leukocytes compared with the control group . Volunteers from the TRF group produced significantly ( P<0.05 ) lower amounts of IL-6 compared with the placebo group . Anti-TT IgG production was also significantly ( P<0.05 ) augmented in the TRF-supplemented group compared with the placebo group . Conclusions : We conclude that TRF has immunostimulatory effects and potential clinical benefits to enhance immune response to vaccines BACKGROUND In most tuberculosis ( TB ) endemic countries , bacillus Calmette-Guérin ( BCG ) is usually given around birth to prevent severe TB in infants . The neonatal immune system is immature . Our hypothesis was that delaying BCG vaccination from birth to 10 weeks of age would enhance the vaccine-induced immune response . METHODS In a r and omized clinical trial , BCG was administered intradermally either at birth ( n=25 ) or at 10 weeks of age ( n=21 ) . Ten weeks after vaccination , and at 1 year of age , vaccine-specific CD4 and CD8 T cell responses were measured with a whole blood intracellular cytokine assay . RESULTS Infants who received delayed BCG vaccination demonstrated higher frequencies of BCG-specific CD4 T cells , particularly polyfunctional T cells co-expressing IFN-gamma , TNF-alpha and IL-2 , and most strikingly at 1 year of age . CONCLUSIONS Delaying BCG vaccination from birth to 10 weeks of age enhances the quantitative and qualitative BCG-specific T cell response , when measured at 1 year of age BACKGROUND Bacille Calmette-Guérin ( BCG ) is a strong T helper 1 incentive and , thus , may contribute to a decreased risk of T helper 2-dependent atopic disease . OBJECTIVE To investigate the natural course of specific immunoglobulin E ( IgE ) responses and atopic disease in  BCG-vaccinated and nonvaccinated children . PARTICIPANTS Seven hundred seventy-four children from a prospect ively followed birth cohort . OUTCOME MEASURES Physical examination and case history were performed at 3 , 6 , 12 , 18 , 24 , 36 , 48 , 60 , 72 , and 84 months of age . Total and specific serum IgE levels to 9 common inhalant and food allergens were determined ( CAP ; Pharmacia , Freiburg , Germany ) at 12 , 24 , 36 , 60 , 72 , and 84 months of age . Purified protein derivative ( PPD ) skin testing was performed at 84 months . RESULTS Period and lifetime prevalences of atopic dermatitis and recurrent wheezing tended to be lower in the BCG-vaccinated group early in life , whereas no such trend was found after the second birthday or for allergic rhinitis . The proportion of children remaining free of clinical manifestations tended to be higher in the BCG-vaccinated group but differences decreased over time . No statistically significant differences were found for total IgE levels ( median ) . Atopic sensitization tended to be lower among BCG-vaccinated children during the first 2 years of life . The diameter of the skin reaction to PPD did not correlate with total serum IgE. Clinical and serologic correlates of atopy were not significantly different between children with a skin test diameter of > /=5 mm and those with a smaller diameter . CONCLUSION These results do not support the hypothesis that BCG vaccination in early infancy is associated with a subsequently markedly decreased risk of atopic sensitization or allergy . In addition , PPD skin test reactivity was not impaired in atopic individuals Bacillus Camette-Guérin ( BCG ) vaccine is the only licensed vaccine against tuberculosis , yet its protective efficacy is highly variable between different geographical regions . We hypothesized that exposure to nontuberculous mycobacteria attenuates BCG immunogenicity by inducing mycobacterial-specific regulatory T cells ( Tregs ) . Gambian neonates were recruited at birth and r and omized to receive  BCG vaccination  either at birth or at 4 1/2 mo . Mycobacterial immune responses were assessed at birth , 4 1/2 , and 9 mo of age . At 4 1/2 mo of age the BCG naive individuals had detectable mycobacterial responses , including increased IL-10 production suggesting environmental priming . Vaccination at birth significantly enhanced Th1 , Th2 , IL-6 , IL-17 , and Treg responses in mycobacterial cultures at 4 1/2 mo compared with the BCG naive group . Analyzing results at 4 1/2 mo postvaccination revealed lower IFN-γ , IL-6 , and IL-17 responses in the delayed BCG vaccine group compared with those vaccinated at birth , but this did not relate to Treg levels prevaccination . When comparing responses pre- and post-BCG vaccination in the delayed vaccine group , there was no priming of mycobacterial IL-17 . Mycobacterial responses waned over 9 mo in those vaccinated at birth , leading to comparable mycobacterial immunity in both groups at 9 mo of age . Overall , these data suggest that vaccination at birth induces a broad Th1/Th2/IL-17/Treg mycobacterial response but the Th1/Th-17 response was reduced when delaying the vaccine . The evidence did not suggest that mycobacterial specific naturally occurring Tregs accounted for this attenuated immunogenicity ABSTRACT Immune responses to exogenous antigens in infant experimental animals display various degrees of Th2 polarization . Preliminary evidence from small human studies suggest a similar age-dependent response pattern to vaccines , but detailed investigations on vaccine immunity during infancy have not yet been undertaken . We report below the results of a comprehensive prospect i ve study on responses to the tetanus component of the diphtheria , tetanus , acellular pertussis ( DTaP ) vaccine in a cohort of 55 healthy children , employing peripheral blood mononuclear cells ( P BMC ) collected at the 2- , 4- , and 6-month vaccinations and at 12 months . Antigen-specific production of interleukin-4 ( IL-4 ) , IL-5 , IL-6 , IL-9 , IL-10 , IL-13 , and gamma interferon ( IFN-γ ) was determined at each sample point , in parallel with polyclonal ( phytohemagglutinin PHA-induced ) cytokine responses . Our results indicate early and persistent Th2 responses to the vaccine , in contrast to a more delayed and transient pattern of IFN-γ production . This initial disparity between the Th1 and Th2 components of the vaccine response was mirrored by patterns of polyclonally induced cytokine production , suggesting that the delayed maturation of the Th1 component of the vaccine response during infancy is secondary to developmental processes occurring within the overall Th cell system Recent epidemiologic data have indicated that adults are the most important reservoir that transmit pertussis to children . However , conventional whole cell pertussis vaccine is contraindicated in adults and children over 7 years of age because of the unacceptably high rate of adverse reactions . The aim of this study is to evaluate the specific cellular immune responses and adverse reactions to a less reactogenic acellular pertussis vaccine in adult volunteers . Eighty healthy medical personnel in Chang Gung Children 's Hospital were enrolled . Volunteers in each group received : ( 1 ) Td + full strength acellular pertussis vaccine ( PT , 1 microgram/0.5 ml ; FHA , 4 micrograms/0.5 ml ) ; ( 2 ) Td + half strength acellular pertussis vaccine ; ( 3 ) Td alone .  Lymphocyte phenotypic analysis , antigen-specific antibody titers , antigen-specific proliferative response and cytokine levels were evaluated before and 1 month after vaccination . Our data revealed : ( 1 ) the adverse reactions were minimal ; ( 2 ) phenotypic analysis showed no non-specific activation of helper T or memory T cell after vaccination ; ( 3 ) both PT and FHA-specific antibody titers increased significantly after vaccination , ( 4 ) PT antigens had a mitogenic effect on cord blood mononuclear cells and peripheral blood mononuclear cells of the adult volunteers ; ( 5 ) FHA-specific T cell proliferative responses significantly increased after vaccination ; ( 6 ) the cytokine production pattern showed predominant activation of Th 1 cells as reflected in increased production of gamma-IFN after vaccination . Acellular pertussis vaccine can effectively induce both humoral and cellular immune response in adults BCG vaccine drives a strong T helper 1 cellular immunity which is essential for the protection against mycobacteria , however recent studies suggest that BCG vaccination can have non-specific beneficial effects unrelated to tuberculosis . In the present cohort study the development of cytokine profiles following BCG vaccination was investigated . Immune responses to PPD were assessed before vaccination and at ages of 5 months , 1 year , and 2 years , followed by BCG scar measurement at 4 years of age . BCG was shown to induce both Th1 and Th2 type responses against PPD at about 5 months of age after vaccination , and while Th1 response was sustained , Th2 responses declined over time . However , BCG scar size was strongly correlated with Th2 responses to PPD at 5 months of age . Importantly , we observed no clear effects of BCG vaccination on innate immune responses in terms of early IL-10 or TNF-α production whereas some alterations in general adaptive immune responses to PHA were observed BACKGROUND Shifts in peak measles incidence to children < 12 months old and the associated high mortality support the study of an early 2-dose measles vaccine regimen . METHODS Fifty-five infants were vaccinated with measles vaccine at age 6 ( n=32 ) or 9 ( n=23 ) months , followed by measles-mumps-rubella (MMR)-II vaccine at age 12 months . A control group received MMR-II only at age 12 months . Measles-specific humoral and cell-mediated immunity were evaluated before , 12 weeks after measles immunization , and 24 weeks after MMR-II . RESULTS Measles-specific T cell proliferation after both doses of vaccine was equivalent , regardless of age or the presence of passive antibodies . Seroconversion rates , geometric mean titers , and the percentage of infants with antibody titers > 120 mIU after the first measles vaccine  were lower in infants vaccinated at age 6 months , regardless of the presence of passive antibodies , but measles humoral responses increased after the administration of MMR-II vaccine in children initially vaccinated at age 6 or 9 months . CONCLUSION Measles vaccination elicits T cell responses in infants as young as 6 months old , which may prime the humoral response to the second dose . Initiating measles vaccination as an early 2-dose regimen results in an immunologic response that is likely to have clinical benefits in developed and developing countries Background No targeted immunotherapies reverse type 1 diabetes in humans . However , in a rodent model of type 1 diabetes , Bacillus Calmette-Guerin ( BCG ) reverses disease by restoring insulin secretion . Specifically , it stimulates innate immunity by inducing the host to produce tumor necrosis factor ( TNF ) , which , in turn , kills disease-causing autoimmune cells and restores pancreatic beta-cell function through regeneration . Methodology /Principal Findings Translating these findings to humans , we administered BCG , a generic vaccine , in a proof-of-principle , double-blind , placebo-controlled trial of adults with long-term type 1 diabetes ( mean : 15.3 years ) at one clinical center in North America . Six subjects were r and omly assigned to BCG or placebo and compared to self , healthy paired controls ( n = 6 ) or reference subjects with ( n = 57 ) or without ( n = 16 ) type 1 diabetes , depending upon the outcome measure . We monitored weekly blood sample s for 20 weeks for insulin-autoreactive T cells , regulatory T cells ( Tregs ) , glutamic acid decarboxylase ( GAD ) and other autoantibodies , and C-peptide , a marker of insulin secretion .  BCG-treated patients and one placebo-treated  patient who , after enrollment , unexpectedly developed acute Epstein-Barr virus infection , a known TNF inducer , exclusively showed increases in dead insulin-autoreactive T cells and induction of Tregs . C-peptide levels ( pmol/L ) significantly rose transiently in two BCG-treated subjects ( means : 3.49 pmol/L [ 95 % CI 2.95–3.8 ] , 2.57 [ 95 % CI 1.65–3.49 ] ) and the EBV-infected subject ( 3.16 [ 95 % CI 2.54–3.69 ] ) vs.1.65 [ 95 % CI 1.55–3.2 ] in reference diabetic subjects . BCG-treated subjects each had more than 50 % of their C-peptide values above the 95th percentile of the reference subjects . The EBV-infected subject had 18 % of C-peptide values above this level . Conclusions / Significance We conclude that BCG treatment or EBV infection transiently modified the autoimmunity that underlies type 1 diabetes by stimulating the host innate immune response . This suggests that BCG or other stimulators of host innate immunity may have value in the treatment of long-term diabetes . Trial Registration Clinical Trials.gov Background Although BCG vaccination is recommended in most countries of the world , little is known of the persistence of BCG-induced immune responses . As novel TB vaccines may be given to boost the immunity induced by neonatal BCG vaccination , evidence concerning the persistence of the BCG vaccine-induced response would help inform decisions about when such boosting would be most effective . Methods A r and omised control study of UK adolescents was carried out to investigate persistence of BCG immune responses . Adolescents were tested for interferon-gamma ( IFN-γ ) response to Mycobacterium tuberculosis purified protein derivative ( M.tb PPD ) in a whole blood assay before , 3 months , 12 months ( n = 148 ) and 3 years ( n = 19 ) after receiving teenage BCG vaccination or 14 years after receiving infant BCG vaccination ( n = 16 ) . Results A gradual reduction in magnitude of response was evident from 3 months to 1 year and from 1 year to 3 years following teenage vaccination , but responses 3 years after vaccination were still on average 6 times higher than before vaccination among vaccinees . Some individuals ( 11/86 ; 13 % ) failed to make a detectable antigen-specific response three months after vaccination , or lost the response after 1 ( 11/86 ; 13 % ) or 3 ( 3/19 ; 16 % ) years . IFN-γ response to Ag85 was measured in a subgroup of adolescents and appeared to be better maintained with no decline from 3 to 12 months . A smaller group of adolescents were tested 14 years after receiving infant BCG vaccination and 13/16 ( 81 % ) made a detectable IFN-γ response to M.tb PPD 14 years after infant vaccination as compared to 6/16 ( 38 % ) matched unvaccinated controls ( p = 0.012 ) ; teenagers vaccinated in infancy were 19 times more likely to make an IFN-γ response of > 500 pg/ml than unvaccinated teenagers . Conclusion BCG vaccination in infancy and adolescence induces immunological memory to mycobacterial antigens that is still present and measurable for at least 14 years in the majority of vaccinees , although the magnitude of the peripheral blood response wanes from 3 months to 12 months and from 12 months to 3 years post vaccination . The data presented here suggest that because of such waning in the response there may be scope for boosting anti-tuberculous immunity in BCG vaccinated children anytime from 3 months post-vaccination . This supports the prime boost strategies being employed for some new TB vaccines currently under development ABSTRACT The lack of a clear correlation between the levels of antibody to pertussis antigens and protection against disease lends credence to the possibility that cell-mediated immunity provides primary protection against disease . This phase I comparative trial had the aim of comparing the in vitro cellular immune response and anti-pertussis toxin ( anti-PT ) immunoglobulin G ( IgG ) titers induced by a cellular pertussis vaccine with low lipopolysaccharide ( LPS ) content ( wPlow vaccine ) with those induced by the conventional whole-cell pertussis ( wP ) vaccine . A total of 234 infants were vaccinated at 2 , 4 , and 6 months with the conventional wP vaccine or the wPlow vaccine .  Proliferation of CD3 + T cells was evaluated by flow cytometry after 6 days of peripheral blood mononuclear cell culture with stimulation with heat-killed Bordetella pertussis or phytohemagglutinin ( PHA ) . CD3 + , CD4 + , CD8 + , and T-cell receptor γδ-positive ( γδ+ ) cells were identified in the gate of blast lymphocytes . Gamma interferon , tumor necrosis factor alpha , interleukin-4 ( IL-4 ) , and IL-10 levels in supernatants and serum anti-PT IgG levels were determined using enzyme-linked immunosorbent assay ( ELISA ) . The net percentage of CD3 + blasts in cultures with B. pertussis in the group vaccinated with wP was higher than that in the group vaccinated with the wPlow vaccine ( medians of 6.2 % for the wP vaccine and 3.9 % for the wPlow vaccine ; P = 0.029 ) . The frequencies of proliferating CD4 + , CD8 + , and γδ+ cells , cytokine concentrations in supernatants , and the geometric mean titers of anti-PT IgG were similar for the two vaccination groups . There was a significant difference between the T-cell sub population s for B. pertussis and PHA cultures , with a higher percentage of γδ+ cells in the B. pertussis cultures ( P < 0.001 ) . The overall data did suggest that wP vaccination result ed in modestly better specific CD3 + cell proliferation , and γδ+ cell expansions were similar with the two vaccines Measles vaccination of infants younger than 1 year of age should be successful in population s with a high proportion of measles vaccinated mothers . Infants whose mothers were vaccinated are born with less maternal antibody which can interfere with vaccination compared with infants whose mothers had measles . AIK-C or Connaught ( CLL ) measles vaccine was given to 300 6 month infants born to mothers who had measles ( group 1 ) or who were vaccinated against measles ( group 2 ) . Pre- and post-vaccination measles antibody was measured by EIA and PRN and cell mediated immunity ( CMI ) by blast transformation and production of interferon-gamma and interleukin-10 . After vaccination , mean antibody level , seroconversion and blastogenesis were significantly lower for group 1 than group 2 ( p < 0.05 ) . Post-vaccination measles IgG was significantly higher for group 2 CLL vaccinees compared with group 2 AIK-C ( p < 0.05 ) ; seroconversion rates were 73 and 63 % , respectively . More than 93 % of group 2 infants had elevated measles IgG after vaccination . About 89 % of all children had some evidence of a blastogenic response . Lymphoproliferation correlated strongly with cytokine production and weakly with IgG. Not all seroresponders had a CMI response and vice versa . AIK-C and CLL vaccines induce strong measles specific T and B immunity in most 6 month infants of vaccinated mothers The immaturity of the immune system increases the susceptibility of young infants to infectious diseases and prevents the induction of protective immune responses by vaccines . We previously reported that Mycobacterium bovis bacillus Calmette-Guérin ( BCG ) vaccination induces a potent Th1 response to mycobacterial Ags in newborns . In this study , we evaluated the influence of BCG on the response to unrelated vaccines given in early life . Newborns were r and omly allocated to one of three study groups receiving BCG at birth , when infants received their first dose of hepatitis B and oral polio vaccines ; at 2 mo of age , when infants received their first dose of diphtheria and tetanus vaccines ; or at 4.5 mo of age , when immune responses to vaccines were measured . Administration of BCG at the time of priming markedly increased the cellular and Ab responses to the hepatitis B vaccine , but had only a limited influence on the cytokine response to tetanus toxoid and no effect on the Ab responses to tetanus and diphtheria toxoids . Although BCG induced a potent Th1-type response to mycobacterial Ags , it promoted the production of both Th1- and Th2-type cytokines in response to unrelated vaccines . The effect of BCG was apparent at the systemic level , as it increased the Ab response to oral polio vaccine . These results demonstrate that BCG influences the immune response to unrelated Ags in early life , likely through its influence on the maturation of dendritic cells To determine the optimal time of Bacillus Calmette-Guerin ( BCG ) vaccination for induction of Th1 immunity , we measured the interferon (IFN)-γ and interleukin (IL)-10 secretion in purified protein derivative (PPD)-stimulated peripheral blood mononuclear cell ( P BMC ) cultures in newborns vaccinated at birth or 2nd month of life . Moreover , role of CD4(+ ) CD25(+ ) T cells was studied by depletion assay at 8th month . Nineteen term and healthy newborns were r and omized into two groups : Group I composed of 10 newborns vaccinated with BCG at birth and the remaining 9 ( group II ) at 2nd month of life . P BMC s were isolated at birth , 2nd and 8th months of age , and PPD-stimulated IL-10 , 5 and IFN-γ secretion were assessed . The same measurements were repeated for IL-10 and IFN-γ after the depletion of CD4(+ ) CD25(+ ) T cells at the 8th month . Children vaccinated at birth demonstrated higher PPD-stimulated IFN-γ and IL-10 levels at 2 months of age when compared to non-vaccinated ones ( p = 0.038 and p = 0.022 , respectively ) , whereas at 8 months , no significant differences were detected between the two groups . Moreover , CD4(+ ) CD25(+)-depleted T-cell cultures result ed in lower PPD-stimulated IL-10 levels in those vaccinated at birth when compared to non-depleted condition at the 8th month ( p < 0.001 ) . BCG at birth upregulated PPD-stimulated IFN-γ secretion at the 2nd month and remained still detectable at 8 month after the vaccination , whereas those vaccinated at the 2nd month of life lacked that increase in IFN-γ response at the same time-point . Furthermore , depletion assays suggest that CD4(+ ) CD25(+ ) T cells are involved in PPD-stimulated IL-10 secretion in response to BCG vaccination Early or low dose antigen exposure can prime the immune system for subsequent responses ; the so-called " prime-boost " effect . In the context of a Sudanese measles vaccine trial , we assessed whether or not such early exposure could influence the response to revaccination . Children received either Connaught high titer vaccine ( CN : n = 53 ; 10(4.7)pfu ) or  meningococcal A + C vaccine as a placebo ( MEN : n = 58 ) at 5 months of age . At 9 months of age , all received st and ard titer Schwarz vaccine ( SCH : 10(3.9)pfu ) . Neutralizing antibodies were measured before initial vaccination and at 9 months of age ( plaque reduction neutralization assay ( PRN ) ) and again at 5 years of age ( syncytium inhibition assay ( SIA ) ) . Lymphoproliferative responses to measles virus ( MV ) antigens were evaluated at 5 years of age . Eleven of the 53 CN-SCH children ( 21 % ) had sub-protective neutralizing antibody titers prior to revaccination ( log PRN 1.5 + /- 0.03 versus 2.9 + /- 0.07 in the remaining 42 children ; P < 0.004 ) . Maternal antibody titers at the time of initial vaccination in these 11 were high ( PRN 2.44 + /- 0.12 versus 1.9 + /- 0.04 ; P < 0.0001 ) . At 5 years of age , neutralizing antibodies were comparable in the 11 CN-SCH poor responders ( log SIA 2.1 + /- 0.09 ) , the remaining CN-SCH children ( 2.2 + /- 0.06 ) and the MEN-SCH group vaccinated only once at 9 months of age ( 2.25 + /- 0.06 ) . In contrast , 7/11 of the CN-SCH poor responders ( 64 % ) had stimulation indices ( SI ) > 3 in response to MV antigens at 5 years of age ( SI 3.1 + /- 0.6 ) compared with only 14 % in the remaining children of the CN-SCH group ( 2.0 + /- 0.3 ; P = 0.05 ) and 8 % in the MEN-SCH group ( 1.4 + /- 0.2 ; P < 0.0003 ) . These data suggest that early measles vaccination in the presence of maternal antibodies can sometimes prime for a balanced humoral and cellular immune response to subsequent revaccination Recent studies have explored the effect of Bacilli Calmette-Guerin ( BCG ) or Mycobacterium vaccae vaccination in asthmatic patients , yielding conflicting results . We investigated the effect of BCG vaccination in asthmatic schoolchildren , especially focusing on the cytokine pattern released by mononuclear cells . After a 1-yr run-in period , 67 asthmatic schoolchildren received intradermal immunization with BCG  ( 33 patients ) or placebo ( 34 patients ) . Both groups were followed during 1 yr . Serum immunoglobulin E ( IgE ) levels did not change after BCG ( 407.1 + /- 86.6 vs. 415.1 + /- 86.7 IU/ml , mean + /- s.e.m . ) , but increased after placebo ( 406.7 + /- 67.0 vs. 619.7 + /- 90.7 IU/ml , p = 0.001 ) administration . Interleukin (IL)-4 and interferon (IFN)-gamma measured in the supernatant of stimulated cultured blood mononuclear cells did not change in the BCG group ( 10.8 + /- 2.3 vs. 17.9 + /- 5.7 pg/ml , and 348.6 + /- 118.0 vs. 354.8 + /- 139.0 pg/ml , respectively ) , while in the control group IL-4 increased ( from 6.7 + /- 1.3 to 16.1 + /- 6.0 pg/ml , p < 0.05 ) , and IFN-gamma decreased ( from 279.9 + /- 82.1 to 232.1 + /- 109.6 pg/ml , p = 0.01 ) . In comparison with their initial status , most patients maintained the same asthma severity and the same proportion of emergency room visits at the end of the study . The proportion of those in whom asthma improved or worsened was the same in both groups . We concluded that , contrary to the common hypothesis , BCG vaccination in asthmatic children was unable to cause a long-term reinforcement of Th(1 ) response , although it could avoid the increased Th(2 ) response observed in control patients New generation pertussis vaccines , containing only purified Bordetella pertussis antigens , have been proven safe , immunogenic and efficacious . They have , however , raised new questions regarding the mechanism of protection from whooping cough and the duration of the immune response following vaccination . In addition to the antibody ( Ab ) titer , the level of pertussis toxin ( PT ) neutralizing antibodies may be very important in protection and the role of cell-ediated immunity needs to be defined . We have previously reported the safety and immunogenicity results of two phase I trials in adult volunteers with two acellular pertussis vaccines containing genetically detoxified PT alone or in combination with filamentous hemagglutinin ( FHA ) and 69 K protein . In this work , we present the results of a long term follow-up study of the immune response in the same vaccinees . We evaluated the Ab response , the PT neutralizing titer and the peripheral blood T cell response up to 4 years following vaccination . Our results show that in adults the level of antibodies to PT , FHA and 69 K and the PT neutralizing titers slightly decline between 2.5 and 12 months after the last vaccine dose , but they remain high in the following 2 - 4 years , showing levels 10 - 100 times higher than pre-vaccination values . The T cell responses were more heterogeneous among vaccinees but they did not show any significant decline throughout the period monitored ABSTRACT Pertussis infection is increasingly recognized in older children and adults , indicating the need of booster immunizations in these age groups . We investigated the induction of pertussis-specific immunity in schoolchildren and adults after booster immunization and natural infection . The expression of mRNA of gamma interferon ( IFN-γ ) , interleukin-2 ( IL-2 ) , IL-4 , and IL-5 in the peripheral blood mononuclear cells ( P BMC s ) was assayed by reverse transcription-PCR . The P BMC s of 17 children immunized with one dose of an acellular vaccine containing pertussis toxin ( PT ) , filamentous hemagglutinin ( FHA ) , and pertactin ( PRN ) significantly proliferated in vitro after stimulation with the vaccine antigens . The P BMC s of seven infected individuals  markedly proliferated in the presence of PT and FHA , but the cells of only two of these subjects responded to PRN . At least one of the antigens induced mRNA for IL-4 and /or IL-5 in the cells of 93 % of tested vaccinees and patients , and FHA induced IFN-γ mRNA in the cells of two-thirds of them . Expression of mRNA for IFN-γ correlated with the production of the cytokine protein . Anti-FHA immunoglobulin G antibodies significantly correlated with FHA-induced proliferative responses both before and after immunization . These results show that booster immunization with acellular pertussis vaccine induces both antibody- and cell-mediated immune responses in schoolchildren . Further , booster immunization and natural infection seem to induce the expression of mRNA of T-helper 1 ( Th1 ) and Th2 type cytokines in similar manners . This observation supports the use of acellular pertussis vaccines for booster immunizations of older children , adolescents , and adults BACKGROUND Bacille Calmette-Guérin ( BCG ) vaccination has important non-specific immune effects . In a r and omized trial in Guinea-Bissau , BCG revaccination was associated with significantly increased survival in children who received diphtheria-tetanus-pertussis (DTP)-booster vaccine before enrolment and in children who did not receive micronutrient supplementation ( MN ) . Within the trial we assessed the immunological effects of BCG revaccination . METHODS Children were r and omized to BCG or nothing .  Blood was sample d 6 - 11 weeks after r and omization ( early sample group ) or 5 - 9 months later ( late sample group ) . In vitro cytokine responses ( interferon (IFN)-γ , interleukin (IL)-13 , tumor-necrosis-factor (TNF)-α , and IL-10 ) were assessed in whole blood cultures stimulated with lipopolysaccharide ( LPS ) , purified protein derivative ( PPD ) or phytohaemagglutinin ( PHA ) . Effect-modification by sex , DTP-booster vaccination and MN was studied . RESULTS Cytokines were measured in 345 infants . BCG was associated with significantly increased IFN-γ ( geometric mean ratio (GMR)=4.54 ( 95 % confidence interval : 3.13 - 6.58 ) ) and IL-13 ( GMR=1.43 ( 1.00 - 2.05 ) ) PPD responses , the effect being strongest in the early sample group . Across all three conditions BCG tended to increase IL-10 ( LPS , PHA , PPD : GMR=1.20 , 1.12 , 1.20 ) , most pronounced in the late sample group . BCG reduced the TNF-α/IL-10 ratio in boys with DTP-booster at bleeding and increased it in those without ( interaction test : p=0.03 ) . In children without MN , BCG was associated with reduced TNF-α response in the early sample group ( p=0.006 ) , and increased IL-10 in the late sample group ( p=0.03 ) . CONCLUSION BCG revaccination result ed in a strong IFN-γ response to PPD , which waned slightly over time . BCG also affected the pro-/anti-inflammatory balance , with reduced TNF-α and increased IL-10 responses to LPS , PHA and PPD . This effect depended on sex , DTP-booster vaccination and micronutrient supplementation , being most pronounced in children who had received DTP-booster before enrolment and children who had not received MN , i.e. the group of children which also had lower mortality after BCG revaccination BACKGROUND The efficacy of BCG vaccines against pulmonary tuberculosis varies between population s , showing no protection in Malawi but 50 - 80 % protection in the UK . To investigate the mechanism underlying these differences , r and omised controlled studies were set up to measure vaccine-induced immune responsiveness to mycobacterial antigens in both population s. METHODS 483 adolescents and young adults in Malawi and 180 adolescents in the UK were tested for interferon-gamma ( IFN-gamma ) response to M tuberculosis purified protein derivative ( PPD ) in a whole blood assay , and for delayed type hypersensitivity ( DTH ) skin test response to tuberculin PPD , before and 1 year after receiving BCG ( Glaxo 1077 ) vaccination or placebo or no vaccine . FINDINGS The percentages of the r and omised individuals who showed IFN-gamma and DTH responses were higher in Malawi than in the UK pre-vaccination-ie , 61 % ( 331/546 ) versus 22 % ( 47/213 ) for IFN-gamma and 46 % ( 236/517 ) versus 13 % ( 27/211 ) for DTH . IFN-gamma responses increased more in the UK than in Malawi , with 83 % ( 101/122 ) and 78 % ( 251/321 ) respectively of the vaccinated groups responding , with similar distributions in the two population s 1 year post-vaccination . The DTH response increased following vaccination in both locations , but to a greater extent in the UK than Malawi . The IFN-gamma and DTH responses were strongly associated , except among vaccinees in Malawi . INTERPRETATION The magnitude of the BCG-attributable increase in IFN-gamma responsiveness to M tuberculosis PPD , from before to 1 year post-vaccination , correlates better with the known levels of protection induced by immunisation with BCG than does the absolute value of the IFN-gamma or DTH response after vaccination . It is likely that differential sensitisation due to exposure to environmental mycobacteria is the most important determinant of the observed differences in protection by BCG between population Measles still causes high mortality in children younger than 1 year of age . Administration of high titre measles vaccines before 7 months of age led to increased overall mortality , raising questions as to the immunological effects of measles vaccine in young infants . We investigated the immune response to st and ard titre vaccines given to children in Bangladesh in a single dose at age 9 months , or two doses at 6 and 9 months . Of the children vaccinated at age 9 months , 95 % serocoverted , compared with 70 % at age 6 months . Delayed-type-hypersensitivity reactions to c and ida antigen were significantly reduced in both vaccine groups at 6 weeks post-vaccination , but responses to other recall antigens studied were not significantly different from controls . In both vaccine groups , peripheral blood lymphocytes isolated at 6 and 24 weeks after vaccination showed significantly higher expression of activation markers upon in vitro stimulation , and a sustained increase in IL-2 production . These findings suggest prolonged immune activation after measles vaccination at the same time as some reduction in delayed hypersensitivity responses . Further study of the clinical effects of these changes is warranted BACKGROUND Recalcitrant warts represent a frustrating challenge for both patients and physicians . Although many destructive and immunotherapeutic modalities are available for the treatment of warts , an ideal , universally effective approach has not been explored to date . Recently , intralesional antigen immunotherapy has shown promising efficacy in the treatment of warts . The aim of the study was to evaluate the efficacy and safety of intralesional measles , mumps , and rubella ( MMR ) vaccine in the treatment of recalcitrant warts . METHODS The study included 70 adult patients with multiple recalcitrant extragenital warts of different sizes and duration s , with or without distant warts . They were directly injected , without a pre-sensitization skin test , with 0.3 intralesional MMR vaccine into the largest wart at 2-week intervals until complete clearance or for a maximum of five treatments . Follow-up was made every month for six months to detect any recurrence .  RESULTS Sixty-five patients , 35 men and 30 women , completed the study , and five patients discontinued for various reasons .  Complete clearance of the lesions was observed in 41 patients ( 63 % ) , partial response in 15 patients ( 23 % ) , and no response in nine patients ( 14 % ) . Complete response was demonstrated in 74.5 % of those presenting with distant warts . Side effects were mild and insignificant in the form of pain during injection , itching , erythema , and edema at the site of injection and flu-like symptoms . Recurrence was detected in two patients only . CONCLUSIONS Intralesional immunotherapy by MMR vaccine is a promising , effective , and safe treatment modality for recalcitrant warts Atopic dermatitis ( AD ) is a chronic inflammatory skin disease , affecting 10 - 20 % of children . Measles vaccination has been reported to have contradictory effects on incidence of AD in children . Therefore , we performed the first prospect i ve , double-blind , placebo-controlled study to analyze the evolution of AD in infants after measles vaccination .  The study included 12 infants ( 10 - 14 months old ) with AD , r and omly assigned to two groups : while the first group received a single dose of a st and ard measles vaccine ROUVAX , the second was treated with placebo ( vehicle ) . Infants were followed-up for 6 months after administration of ROUVAX/placebo for the clinical signs associated with AD , by determination of SCORAD index . In addition , serum was taken before vaccination and 1 month later to determine the presence of seroconversion and to analyze the progression of serum levels of CCL18 ( PARC ) and E-selectin , known to be distinct serum markers that reflect clinical features of AD . In the vaccinated group , five of six children seroconverted 1 month after treatment and one infant showed a 50 % improvement of SCORAD . Serum levels of CCL18 were significantly decreased in two treated infants ( of four analyzed for this group ) and E-selectin slightly decreased in one infant ( of three analyzed by this test ) . In placebo-treated group the SCORAD improved in one patient and serum levels of CCL18 and E-selectin did not change . These data suggest that measles vaccination not only does not aggravate AD , but may also improve some of the immunological parameters of this allergic disease . Inclusion of a higher number of patients in a similar study should give a more comprehensive overview of the benefit of measles vaccination on the clinical evolution of AD patients , and potentially open new avenues to the clinical application of the anti-inflammatory effect of measles virus proteins Epidemiological evidence links T-helper type 2 ( Th2 ) cytokine responses to the pathogenesis of atopy/asthma . It is hypothesized that certain immunizations may induce/amplify Th2 cytokine responses . The objective of this study was to determine whether Th cytokine responses to immunization with tetanus toxoid differ in adults with and without allergic rhinitis ( AR ) . Thirty subjects were enrolled ( 15 AR and 15 non-AR subjects as confirmed by history and allergy skin testing ) . Blood was collected before ( day 0 ) and on days 3 , 7 , 14 , and 28 after immunization with tetanus toxoid . Peripheral blood mononuclear cells ( PMNCs ) were purified and cultured with either PHA or tetanus toxoid for 2 or 6 days , respectively . Supernatants were harvested and assayed for IFN-gamma and IL-13 levels ( pg/mL ) by EIA . Results were normalized by log transformation and analyzed by stepwise regression . Baseline ( day 0 ) cytokine values were similar in both groups . PHA and tetanus-induced IFN-gamma were increased ( p < 0.05 ) in non-AR ( 3.2 + /- 0.3 and 1.4 + /- 0.3 on day 7 , and 3.5 + /- 0.2 and 1.9 + /- 0.2 on day 14 , respectively ) compared with AR subjects ( 2.3 + /- 0.3 and 0.9 + /- 0.3 on day 7 , and 2.7 + /- 0.3 and 1.2 + /- 0.3 on day 14 , respectively ) . PHA-induced , but not tetanus-induced , IL-13 production was increased ( p < 0.05 ) in non-AR compared with AR subjects on day 7 ( p < 0.05 ) . PHA-induced IL-13 production was 3.1 + /- 0.2 in non-AR and 2.6 + /- 0.3 in AR subjects on day 7 . These results indicate differential Th cytokine responses in AR and non-AR subjects after immunization with tetanus toxoid . Future studies are warranted and may result in the identification of potential prevention/treatment strategies for atopy/asthma The effects of measles immunization on immune responses in infants and the roles of vaccine strain and age of immunization are not known . Eighty-eight children were immunized at 6 or 9 months of age with the Edmonston-Zagreb ( EZ ) or Schwarz ( SW6 , SW9 ) strain of measles vaccine . Children were studied before and 2 weeks and 3 months after immunization . Seroconversion was similar , but geometric mean neutralizing titers at 3 months differed by vaccine group : SW9 , 1367 mIU/mL ; SW6 , 982 ; and EZ , 303 ( P = .003 ) . Mitogen-induced lymphoproliferation was decreased at 2 weeks in the SW9 group and at 3 months in all groups and was negatively correlated with measles antibody level at 3 months ( r = -.387 , P = .003 ) . CD8 T cells , soluble CD8 , neopterin , and beta2-microglobulin were increased at 2 weeks in the SW9 group , and soluble CD8 and beta2-microglobulin remained elevated at 3 months . Therefore , measles immunization result ed in suppression of lymphoproliferation , which was most evident in infants with the highest antibody responses and most immune activation Background : The 2-fold increase in female mortality after high-titer measles vaccine may have occurred because many children received diphtheria-tetanus-pertussis ( DTP ) vaccine or inactivated polio vaccine ( IPV ) after high-titer measles vaccine . Objective : We examined whether DTP vaccine and IPV were associated with increased female mortality when they were the most recent vaccine administered to children who had not received measles vaccine . Setting and Design : IPV was used as a control vaccine in 4 r and omized trials of early measles vaccination ( MV ) with enrollment at 4–6 months of age conducted in Guinea-Bissau . Many children had not received all 3 DTP vaccinations before enrollment , and therefore received DTP after IPV or MV . We examined whether DTP vaccination status at enrollment affected the female-male mortality ratio . Population : 9544 children enrolled in 4 trials . Main outcome measure : The female-male mortality ratio in different vaccine groups . Results : Females had a higher mortality rate than males among children r and omized to receive IPV ( mortality rate ratio [ MR ] 1.52 , 95 % CI 1.02–2.28 ) , but females had a similar mortality rate to males among children r and omized to receive MV ( MR 1.01 , 0.69–1.46 ) and among children in the IPV group after they had received MV at 9 months of age or later ( MR 0.88 , 0.68–1.14 ) . Children who had not received a third dose of DTP before enrollment ( and were likely to receive DTP after MV or IPV ) tended to have a higher mortality than children who had received all 3 doses of DTP ( MR 1.30 , 0.97–1.73 ) . This effect was seen only among girls ( MR 1.61 , 1.08–2.40 ) and not among boys ( MR 1.02 , 0.67–1.54 ) . Girls had a lower mortality when MV was the most recent vaccine received rather than DTP or IPV ( MR 0.49 , 0.28–0.87 ) . Conclusions : R and omization to IPV was associated with higher female than male mortality . However , the increased female mortality might result from additional doses of DTP received after enrollment and before measles vaccination Vitamin A supplementation ( VAS ) at birth was not associated with improved survival in a r and omised , placebo-controlled trial in Guinea-Bissau . However , a negative sex-differential effect , which became evident after diphtheria-tetanus-pertussis ( DTP ) vaccination , was noted ; among girls who had received DTP , VAS at birth was associated with two-fold higher mortality than placebo . The objective of the present study was to investigate the immunological effects of VAS at birth within a subgroup of participants in the r and omised trial . Guided by the mortality results , we further explored whether VAS had a differential effect according to sex and DTP status . At 6 weeks after r and omisation and supplementation , we measured differential leucocyte counts and TNF-α , interferon-γ , IL-10 , IL-13 and IL-5 production in a whole-blood culture assay . A total of 471 children were included .  VAS compared with placebo at birth was associated with a higher proportion of monocytes ( relative risk ratio 1·26 , 95 % CI 1·07 , 1·49 , P=0·04 ) , while spontaneous TNF-α production was lower in the VAS group ( geometric mean ratio 0·54 , 95 % CI , 0·37 , 0·78 , P=0·001 ) . Stratified analysis showed that VAS was associated with lower TNF-α and IL-10 production for girls without DTP and boys with DTP , result ing in significant three-way interactions between VAS , sex and DTP vaccination status ( P=0·03 and P=0·04 , respectively ) for spontaneous TNF-α and IL-10 production . The results substantiate the potential role of VAS as an immunomodulatory intervention , which has different effects depending on concomitant health interventions and the sex of the recipient The neonatal immune system is immature and may be affected by Bacillus Calmette-Guèrin ( BCG ) vaccine . We investigated the influence of BCG given at two different ages on the peripheral blood ( PB ) T-cell sub population s. Forty full term healthy newborns were r and omly chosen . Twenty of them were vaccinated with BCG at birth ( group I ) and the remaining at the age of 2 months ( group II ) . The cell analysis were carried out before ( pre-BCGI and pre-BCGII ) , and 2 months after ( post-BCGI and post-BCGII ) the vaccination . The analysis of the gamma/delta and alpha/beta T-cell receptor ( TCR ) antigens was done by two-colour flowcytometer . The purified protein derivative ( PPD ) response was investigated 2 months after vaccination . The results showed that although T-cell ( TCR+ cell ) counts showed no difference in PB before and after vaccination in both study groups , the total lymphocyte and non-T cell ( TCR- cell ) population s increased significantly whereas alphabetaT-cell population significantly decreased after vaccination . On the contrary , gammadeltaT-cell counts in PB increased significantly 2 months after vaccination in group I but not in group II . Total lymphocyte and non-T cell counts in vaccinated infants at 2 months of age ( post-BCGI ) were significantly higher than in unvaccinated infants of the same age whereas alphabetaT-cell count in vaccinated infants was significantly low . However , total T-cell and gammadeltaT-cell counts showed no difference . PPD positivity was similar in both study groups ( 61 % in group I , 66 % in group II ) . Neither alphabetaT- nor gammadeltaT-cell counts were different in PPD positive and PPD negative infants . Our study shows that BCG causes marked quantitative changes in the PB T-cell sub population s in young infants Interferon (IFN)-gamma responsiveness to 12 purified protein derivative ( PPD ) and new tuberculin antigens from 9 species of mycobacteria was assessed , using a whole blood assay , in 616 young adults living in northern Malawi , where Mycobacterium bovis bacille Calmette-Guérin ( BCG ) vaccination provides no protection against pulmonary tuberculosis . The prevalence of IFN-gamma responsiveness was highest for PPDs of M. avium , M. intracellulare , and M. scrofulaceum ( the MAIS complex ) . Correlations between responsiveness paralleled genetic relatedness of the mycobacterial species . A r and omized , controlled trial was carried out , to assess the increase in IFN-gamma responsiveness to M. tuberculosis PPD that can be attributed to M. bovis BCG vaccination . The BCG-attributable increase in IFN-gamma response to M. tuberculosis PPD was greater for individuals with low initial responsiveness to MAIS antigens than for those with high initial responsiveness . Although not statistically significant , the trend is consistent with the hypothesis that prior exposure to environmental mycobacteria interferes with immune responses to BCG vaccination ABSTRACT To investigate the role of innate immunity in variable efficacy of  Mycobacterium bovis BCG vaccination in Malawi and the United Kingdom , we examined 24-h tumor necrosis factor alpha , interleukin-1β ( IL-1β ) , and IL-10 responses to mycobacterial purified protein derivatives ( PPDs ) . The rank order in stimulatory potency for different PPDs was the same for all three cytokines . Before vaccination Malawians made higher pro- and anti-inflammatory responses than did United Kingdom subjects . Fewer than 5 % of United Kingdom subjects  made IL-10 in response to any PPD , compared to 19 to 57 % responders among Malawians . Priming for regulatory IL-10 may contribute to the smaller increase in gamma interferon responses in Malawians compared to United Kingdom subjects following BCG vaccination Cytokines play an important role in the immune response to live measles virus immunization  . To gain further insight into the cytokine production profile in response to measles vaccination , we studied interferon-gamma ( IFN-gamma ) , tumor necrosis factor ( TNF-alpha ) , soluble IL-2 receptor ( sIL-2R ) , interleukin-2 ( IL-2 ) , interleukin-4 ( IL-4 ) , and interleukin-6 ( IL-6 ) in both supernatants from peripheral blood mononuclear cells ( P BMC ) stimulated with phytohaemagglutinin ( PHA ) , and plasma . We enrolled 57 healthy infants and children residing in an area where no measles virus circulated in their lifetimes . Overall analysis of cytokines in supernatants from P BMC showed that a predominant Th1 cytokine pattern occurs after the second dose of measles immunization . However , plasma levels of Th1 cytokines ( IFN-gamma , sIL-2R and TNF-alpha ) were preferentially activated by measles virus after the first dose of measles vaccination . Median IFN-gamma plasma levels were 1.73 pg/ml for infants compared to 0.63 pg/ml for older children ( P = 0.003 ) . These data suggest that after the first and the second dose of measles virus immunization , there is a predominant Th1-type directed immune response , but the Th1 cytokine pattern seems to be stronger in previously unvaccinated children . There was no correlation between cytokine production by P BMC supernatants after PHA stimulation and circulating levels of plasma cytokines . No relationship was found between any specific cytokine level and measles antibody level Data obtained in animals indicate that neonatal immune responses are biased toward Th2 . This could reduce the efficacy of vaccines against viral and mycobacterial diseases . The ability of human newborns to develop a Th1 immune response upon immunization has not been studied . Since the vaccine Mycobacterium bovis bacillus Calmette-Guérin ( BCG ) triggers a Th1-type response in adults , we investigated whether it induces a similar response in newborns and whether age at vaccination influences immunogenicity . We found that BCG vaccination at birth induces a memory Th1-type response of similar magnitude to that when given later in life . This study demonstrates that human newborns can be immunized against pathogens controlled by a Th1 immune response Synthesized T-cell epitopes of tetanus toxin are universally immunogenic and serve to enhance immune response when they are used as vaccine carriers of B-cell epitopes . The immunogenicity of the P2 , P30 , and P2P30 T-cell epitopes of tetanus toxin and whole tetanus toxoid ( TT ) was evaluated by in vitro proliferation assay of lymphocytes from men with no history of tetanus vaccination who were enrolled in a malaria prophylaxis trial . The enhancement of immune response by tetanus vaccination ( Td ) and possible antagonism by the antimalarial drugs , was measured by pre- and post-Td comparisons within and between immunized prophylaxis groups ( primaquine , chloroquine , placebo ) and a nonimmunized control group . Constructs demonstrated low immunogenicity relative to TT in all groups . Relative to both control and its own baseline , the immunized primaquine prophylaxis group was distinct in demonstrating significantly increased proliferation against all three subunits and at both high ( 30 microg ml(-1 ) ) and low ( 3 microg ml(-1 ) ) concentrations . Immunization elicited significantly increased proliferation responses by placebo and chloroquine prophylaxis groups against only the P2P30 construct . Despite these significant post-Td changes , a low concentration of TT 0.1 microg ml(-1 ) ) stimulated proliferation 7 - 10 times over that induced by the greatest concentration of the constructs Bacille Calmette-Guérin ( BCG ) immunity can be studied as one experimental model for mycobacterial protective immunity . We have used flow cytometry to investigate human T cell subsets induced by BCG vaccination . P BMC harvested from BCG-vaccinated individuals and controls were stimulated with mycobacterial Ags , and the T cell subsets present after 7 days of in vitro expansion were characterized . The most dramatic expansions induced by mycobacterial Ags were detected in gamma delta T cells . The gamma delta T cell expansions measured after in vitro stimulation with mycobacterial Ags were significantly greater in BCG responders compared with nonsensitized controls , indicating that BCG vaccination induced gamma delta T cell activation associated with enhanced secondary responses . The majority of gamma delta T cells induced by BCG vaccination were gamma 9 + delta 2 + T cells reactive with isoprenyl pyrophosphates . Coculture with CD4 + T cells induced optimal gamma delta T cell expansion , although IL-2 alone could provide this helper function in the absence of CD4 + T cells . Gamma delta T cells were found to provide helper functions for mycobacterial specific CD4 + and CD8 + T cells as well , demonstrating reciprocal stimulatory interactions between gamma delta T cells and other T cell subsets . Finally , prominent mycobacterial specific gamma delta T cell expansions were detected in a subset of unvaccinated controls with evidence for prior sensitization to mycobacterial lysates ( elevated mycobacterial specific lymphoproliferative responses ) . These latter findings are consistent with the hypothesis that exposure to atypical mycobacteria or related environmental Ags may induce gamma delta T cells cross-reactive with Ags present in the Mycobacterium tuberculosis complex . Our results suggest that gamma delta T cells may be capable of developing a memory immune-like phenotype , and therefore might be important targets for new vaccines Recent studies have indicated that type 1 T cell responses ( potent interferon-gamma and cytolytic responses , with absence of interleukin-4 production ) are important for protective immunity against mycobacteria . These observations suggest that assays of type 1 T cell responses may be useful as surrogate markers of protective immunity in the evaluation of new tuberculosis vaccines . To be useful as surrogate markers , immunologic assays must distinguish between vaccine recipients and control subjects in clinical trials . Previous studies have shown that bacille Calmette-Guérin ( BCG ) vaccination can induce human type 1 T cell responses , but r and omized trials have not been done to determine whether measurement of these responses can distinguish between BCG recipients and control subjects . We have conducted a double-blind , placebo-controlled trial of intradermal vaccination with two different BCG strains . We compared the mean lymphoproliferative , cytotoxic , Th1 and Th2 cytokine , and antibody responses detected in BCG and placebo recipients . These studies demonstrated that significant increases in Mycobacterium-specific T cell proliferative responses and type 1 cytokine responses were induced by BCG when compared with results with a placebo . In addition , BCG induced significant increases in Mycobacterium-specific antibody responses with an isotype profile characteristic of a type 1 cytokine bias . T cell and antibody assays involving the use of mycobacterial whole cell lysates or live BCG were able to discriminate between BCG and placebo recipients better than were assays using mycobacterial culture filtrates . These studies provide important information for the development of immunologic assays that might be useful as surrogate markers of protective immunity in future trials of new tuberculosis vaccines
OBJECTIVE To identify and characterise non-specific immunological effects after routine childhood vaccines against BCG , measles , diphtheria , pertussis , and tetanus .
The primary aim was to systematic ally identify , assemble , and review all available studies and data on the possible non-specific or heterologous immunological effects of BCG ; measles ; mumps , measles , and rubella ( MMR ) ; diphtheria ; tetanus ; and pertussis vaccines .