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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

Association of Men C- and Men Y- specific memory B cells with SBA titre pre- and post- boost.Men C-specific memory B cells at M6 and M7 were plotted against log-transformed M12 Men C SBA (A and B) and M13 SBA (C and D). M12 Men C-specific memory B cells were plotted against log-transformed M13 SBA values (E). Men Y-specific memory B cells at M6 and M7 were plotted against log-transformed M12 Men Y SBA (F and G) and M13 SBA (H and I). M12 Men Y-specific memory B cells were plotted against log-transformed M13 SBA values (J). Linear regression analyses were performed to determine statistically significant associations where r = r2 value, n = number of subjects and p(*)≤0.05.
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pone.0133126.g003: Association of Men C- and Men Y- specific memory B cells with SBA titre pre- and post- boost.Men C-specific memory B cells at M6 and M7 were plotted against log-transformed M12 Men C SBA (A and B) and M13 SBA (C and D). M12 Men C-specific memory B cells were plotted against log-transformed M13 SBA values (E). Men Y-specific memory B cells at M6 and M7 were plotted against log-transformed M12 Men Y SBA (F and G) and M13 SBA (H and I). M12 Men Y-specific memory B cells were plotted against log-transformed M13 SBA values (J). Linear regression analyses were performed to determine statistically significant associations where r = r2 value, n = number of subjects and p(*)≤0.05.

Mentions: There was a significant positive association between M12 Men C-specific memory B cells and M13 Men C-specific SBA titre (Fig 3E; *r = 0.1488). Whilst there were positive associations between Men C-specific memory B cells and SBA titre at other time points, these were not significant (Fig 3A–3D). All associations between Men Y-specific memory B cells and SBA were not significant (Fig 3F–3J).


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)

Association of Men C- and Men Y- specific memory B cells with SBA titre pre- and post- boost.Men C-specific memory B cells at M6 and M7 were plotted against log-transformed M12 Men C SBA (A and B) and M13 SBA (C and D). M12 Men C-specific memory B cells were plotted against log-transformed M13 SBA values (E). Men Y-specific memory B cells at M6 and M7 were plotted against log-transformed M12 Men Y SBA (F and G) and M13 SBA (H and I). M12 Men Y-specific memory B cells were plotted against log-transformed M13 SBA values (J). Linear regression analyses were performed to determine statistically significant associations where r = r2 value, n = number of subjects and p(*)≤0.05.
© Copyright Policy
Related In: Results  -  Collection

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

pone.0133126.g003: Association of Men C- and Men Y- specific memory B cells with SBA titre pre- and post- boost.Men C-specific memory B cells at M6 and M7 were plotted against log-transformed M12 Men C SBA (A and B) and M13 SBA (C and D). M12 Men C-specific memory B cells were plotted against log-transformed M13 SBA values (E). Men Y-specific memory B cells at M6 and M7 were plotted against log-transformed M12 Men Y SBA (F and G) and M13 SBA (H and I). M12 Men Y-specific memory B cells were plotted against log-transformed M13 SBA values (J). Linear regression analyses were performed to determine statistically significant associations where r = r2 value, n = number of subjects and p(*)≤0.05.
Mentions: There was a significant positive association between M12 Men C-specific memory B cells and M13 Men C-specific SBA titre (Fig 3E; *r = 0.1488). Whilst there were positive associations between Men C-specific memory B cells and SBA titre at other time points, these were not significant (Fig 3A–3D). All associations between Men Y-specific memory B cells and SBA were not significant (Fig 3F–3J).

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