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Human Infant Memory B Cell and CD4+ T Cell Responses to HibMenCY-TT Glyco-Conjugate Vaccine.

Fuery A, Richmond PC, Currie AJ - PLoS ONE (2015)

Bottom Line: Polysaccharide-specific Men C- but not Men Y- specific memory B cell frequencies pre-boost (12 months) were significantly associated with post-boost (13 months) SBA titres.TT-specific CD4+ T cells were detected at frequencies between 0.001 and 0.112 as a percentage of CD3+ T cells, but their numbers were not associated with SBA titres.There were significant negative associations between SBA titres at M13 and cytokine expression at M7 and M12.

View Article: PubMed Central - PubMed

Affiliation: School of Paediatrics and Child Health, The University of Western Australia, 35 Stirling Highway, Perth, WA 6009, Australia; Wesfarmers Centre for Vaccines and Infectious Diseases, Telethon Kids Institute, The University of Western Australia, 100 Roberts Road, Perth, WA 6008, Australia.

ABSTRACT

Unlabelled: Carrier-specific T cell and polysaccharide-specific B cell memory responses are not well characterised in infants following glyco-conjugate vaccination. We aimed to determine if the number of Meningococcal (Men) C- and Y- specific memory B cells and; number and quality of Tetanus Toxoid (TT) carrier-specific memory CD4+ T cells are associated with polysaccharide-specific IgG post HibMenCY-TT vaccination. Healthy infants received HibMenCY-TT vaccine at 2, 4 and 6 months with a booster at 12 months. Peripheral blood mononuclear cells were isolated and polysaccharide-specific memory B cells enumerated using ELISpot. TT-specific memory CD4+ T cells were detected and phenotyped based on CD154 expression and intracellular TNF-α, IL-2 and IFN-γ expression following stimulation. Functional polysaccharide-specific IgG titres were measured using the serum bactericidal activity (SBA) assay. Polysaccharide-specific Men C- but not Men Y- specific memory B cell frequencies pre-boost (12 months) were significantly associated with post-boost (13 months) SBA titres. Regression analysis showed no association between memory B cell frequencies post-priming (at 6 or 7 months) and SBA at 12 months or 13 months. TT-specific CD4+ T cells were detected at frequencies between 0.001 and 0.112 as a percentage of CD3+ T cells, but their numbers were not associated with SBA titres. There were significant negative associations between SBA titres at M13 and cytokine expression at M7 and M12.

Conclusion: Induction of persistent polysaccharide-specific memory B cells prior to boosting is an important determinant of secondary IgG responses in infants. However, polysaccharide-specific functional IgG responses appear to be independent of the number and quality of circulating carrier-specific CD4+ T cells after priming.

No MeSH data available.


Related in: MedlinePlus

Men C- and Men Y- specific SBA titres following HibMen CY-TT vaccine.A. Men C- and B. Men Y- specific SBA titre after 2 (M6) or 3 (M7) priming doses, and prior to (M12) and 1 month post (M13) the booster dose of HibMenCY-TT vaccine. Red dots represent paired samples from individuals who had blood taken following 2 doses of HibMenCY-TT prime, whilst black dots represent those samples from individuals who had blood taken after 3 doses of HibMenCY-TT prime. Horizontal bars indicate median values. The dashed line represents the assay limit of detection. p(**)≤0.01 and p(*)≤0.05 indicating significance of independent samples Mann-Whitney U tests or related samples Wilcoxon signed rank tests.
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pone.0133126.g001: Men C- and Men Y- specific SBA titres following HibMen CY-TT vaccine.A. Men C- and B. Men Y- specific SBA titre after 2 (M6) or 3 (M7) priming doses, and prior to (M12) and 1 month post (M13) the booster dose of HibMenCY-TT vaccine. Red dots represent paired samples from individuals who had blood taken following 2 doses of HibMenCY-TT prime, whilst black dots represent those samples from individuals who had blood taken after 3 doses of HibMenCY-TT prime. Horizontal bars indicate median values. The dashed line represents the assay limit of detection. p(**)≤0.01 and p(*)≤0.05 indicating significance of independent samples Mann-Whitney U tests or related samples Wilcoxon signed rank tests.

Mentions: SBA responses were representative of the larger cohort studied [15], reflecting a typical infant response to meningococcal conjugate vaccine with a good primary response, rapid waning and an anamnestic booster SBA response (Fig 1). Prior to boosting at month (M) 12, there was a significant decrease (**p<0.001 and *p = 0.026 respectively) in Men C- and Men Y- specific SBA titres from those at M7 (Fig 1). Compared to M6, Men C-specific SBA titres at M12 were significantly reduced (*p = 0.027) but the difference was not significant for Men Y. A booster dose of HibMenCY-TT significantly increased both Men C- and Men Y- specific SBA titres (**p<0.001 for both), with all subjects achieving titres above the protective threshold at M13.


Human Infant Memory B Cell and CD4+ T Cell Responses to HibMenCY-TT Glyco-Conjugate Vaccine.

Fuery A, Richmond PC, Currie AJ - PLoS ONE (2015)

Men C- and Men Y- specific SBA titres following HibMen CY-TT vaccine.A. Men C- and B. Men Y- specific SBA titre after 2 (M6) or 3 (M7) priming doses, and prior to (M12) and 1 month post (M13) the booster dose of HibMenCY-TT vaccine. Red dots represent paired samples from individuals who had blood taken following 2 doses of HibMenCY-TT prime, whilst black dots represent those samples from individuals who had blood taken after 3 doses of HibMenCY-TT prime. Horizontal bars indicate median values. The dashed line represents the assay limit of detection. p(**)≤0.01 and p(*)≤0.05 indicating significance of independent samples Mann-Whitney U tests or related samples Wilcoxon signed rank tests.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4507978&req=5

pone.0133126.g001: Men C- and Men Y- specific SBA titres following HibMen CY-TT vaccine.A. Men C- and B. Men Y- specific SBA titre after 2 (M6) or 3 (M7) priming doses, and prior to (M12) and 1 month post (M13) the booster dose of HibMenCY-TT vaccine. Red dots represent paired samples from individuals who had blood taken following 2 doses of HibMenCY-TT prime, whilst black dots represent those samples from individuals who had blood taken after 3 doses of HibMenCY-TT prime. Horizontal bars indicate median values. The dashed line represents the assay limit of detection. p(**)≤0.01 and p(*)≤0.05 indicating significance of independent samples Mann-Whitney U tests or related samples Wilcoxon signed rank tests.
Mentions: SBA responses were representative of the larger cohort studied [15], reflecting a typical infant response to meningococcal conjugate vaccine with a good primary response, rapid waning and an anamnestic booster SBA response (Fig 1). Prior to boosting at month (M) 12, there was a significant decrease (**p<0.001 and *p = 0.026 respectively) in Men C- and Men Y- specific SBA titres from those at M7 (Fig 1). Compared to M6, Men C-specific SBA titres at M12 were significantly reduced (*p = 0.027) but the difference was not significant for Men Y. A booster dose of HibMenCY-TT significantly increased both Men C- and Men Y- specific SBA titres (**p<0.001 for both), with all subjects achieving titres above the protective threshold at M13.

Bottom Line: Polysaccharide-specific Men C- but not Men Y- specific memory B cell frequencies pre-boost (12 months) were significantly associated with post-boost (13 months) SBA titres.TT-specific CD4+ T cells were detected at frequencies between 0.001 and 0.112 as a percentage of CD3+ T cells, but their numbers were not associated with SBA titres.There were significant negative associations between SBA titres at M13 and cytokine expression at M7 and M12.

View Article: PubMed Central - PubMed

Affiliation: School of Paediatrics and Child Health, The University of Western Australia, 35 Stirling Highway, Perth, WA 6009, Australia; Wesfarmers Centre for Vaccines and Infectious Diseases, Telethon Kids Institute, The University of Western Australia, 100 Roberts Road, Perth, WA 6008, Australia.

ABSTRACT

Unlabelled: Carrier-specific T cell and polysaccharide-specific B cell memory responses are not well characterised in infants following glyco-conjugate vaccination. We aimed to determine if the number of Meningococcal (Men) C- and Y- specific memory B cells and; number and quality of Tetanus Toxoid (TT) carrier-specific memory CD4+ T cells are associated with polysaccharide-specific IgG post HibMenCY-TT vaccination. Healthy infants received HibMenCY-TT vaccine at 2, 4 and 6 months with a booster at 12 months. Peripheral blood mononuclear cells were isolated and polysaccharide-specific memory B cells enumerated using ELISpot. TT-specific memory CD4+ T cells were detected and phenotyped based on CD154 expression and intracellular TNF-α, IL-2 and IFN-γ expression following stimulation. Functional polysaccharide-specific IgG titres were measured using the serum bactericidal activity (SBA) assay. Polysaccharide-specific Men C- but not Men Y- specific memory B cell frequencies pre-boost (12 months) were significantly associated with post-boost (13 months) SBA titres. Regression analysis showed no association between memory B cell frequencies post-priming (at 6 or 7 months) and SBA at 12 months or 13 months. TT-specific CD4+ T cells were detected at frequencies between 0.001 and 0.112 as a percentage of CD3+ T cells, but their numbers were not associated with SBA titres. There were significant negative associations between SBA titres at M13 and cytokine expression at M7 and M12.

Conclusion: Induction of persistent polysaccharide-specific memory B cells prior to boosting is an important determinant of secondary IgG responses in infants. However, polysaccharide-specific functional IgG responses appear to be independent of the number and quality of circulating carrier-specific CD4+ T cells after priming.

No MeSH data available.


Related in: MedlinePlus