Dataset Information

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

ABSTRACT: 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-?, IL-2 and IFN-? 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.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.

SUBMITTER: Fuery A

PROVIDER: S-EPMC4507978 | biostudies-literature | 2015

REPOSITORIES: biostudies-literature

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

Fuery Angela A Richmond Peter C PC Currie Andrew J AJ

PloS one 20150720 7

<h4>Unlabelled</h4>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 ...[more]

PMID: 26191794

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Project description:A new serogroup A meningococcal conjugate vaccine (PsA-TT, MenAfriVac™) has been developed to combat devastating serogroup A Neisseria meningitis (MenA) epidemics in Africa. A mass immunization campaign targeting 1-29 year olds was conducted in Burkina Faso in December 2010. Protection of subsequent infant cohorts will be necessary through either introduction of PsA-TT into the routine Expanded Programme on Immunization (EPI) or periodic repeat mass vaccination campaigns.To inform future immunization policy for PsA-TT vaccination of infants through a comparison of PsA-TT campaign vaccination coverage and routine measles-containing vaccine (MCV) coverage in Burkina Faso.A national survey was conducted in Burkina Faso during December 17-27, 2011 using stratified cluster sampling to assess PsA-TT vaccine coverage achieved by the 2010 nationwide immunization campaign among 2-30 year olds and routine MCV coverage among 12-23 month olds. Coverage estimates and 95% Confidence Intervals (CI) were calculated, reasons for non-vaccination and methods of campaign communication were described, and a multivariable analysis for factors associated with vaccination was conducted.National overall PsA-TT campaign coverage was 95.9% (95% CI: 95.0-96.7) with coverage greater than 90% all 13 regions of Burkina Faso. National overall routine MCV coverage was 92.5% (95% CI: 90.5-94.1), but ranged from 75.3% to 95.3% by region. The primary predictor for PsA-TT vaccination among all age groups was a head of household informed of the campaign. PsA-TT vaccination was more likely in residents of rural settings, whereas MCV vaccination was more likely in residents of urban settings.Overall national vaccination rates in Burkina Faso were similar for PsA-TT and MCV vaccine. The regions with MCV coverage below targets may be at risk for sub-optimal vaccination coverage if PsA-TT is introduced in EPI. These results highlight the need for assessments of routine vaccination coverage to guide PsA-TT immunization policy in meningitis belt countries.

Project description:Through the interaction of T follicular helper (Tfh) cells and B cells, efficacious vaccines can generate high-affinity, pathogen-neutralizing antibodies, and memory B cells. Using CXCR5, CXCR3, CCR6, CCR7, PD1, and ICOS as markers, Tfh-like cells can be identified in the circulation and be classified into three functionally distinct subsets that are PD1+ICOS+, PD1+ ICOS-, or PD1-ICOS-. We used these markers to identify different subsets of CXCR5+CD4+ Tfh-like cells in response to highly immunogenic and efficacious vaccines for human papillomaviruses (HPV): Cervarix and Gardasil. In this small study, we used PBMC samples from 11 Gardasil recipients, and 8 Cervarix recipients from the Vaccine Research Center 902 Study to examine the induction of circulating Tfh-like cells and IgD-CD38HiCD27+ memory B cells by flow cytometry. PD1+ICOS+ CXCR3+CCR6-CXCR5+CD4+ (Tfh1-like) cells were induced and peaked on Day (D) 7 post-first vaccination, but not as much on D7 post-third vaccination. We also observed a trend toward increase in PD1+ICOS+ CXCR3-CCR6-CXCR5+CD4+ (Tfh2-like) cells for both vaccines, and PD1+ICOS+ CXCR3-CCR6+CXCR5+CD4+ (Tfh17-like) subset was induced by Cervarix post-first vaccination. There were also minimal changes in the other cellular subsets. In addition, Cervarix recipients had more memory B cells post-first vaccination than did Gardasil recipients at D14 and D30. We found frequencies of memory B cells at D30 correlated with anti-HPV16 and 18 antibody titers from D30, and the induction levels of memory B cells at D30 and PD1+ICOS+Tfh1-like cells at D7 post-first vaccination correlated for Cervarix. Our study showed that induction of circulating CXCR5+CD4+ Tfh-like subsets can be detected following immunization with HPV vaccines, and potentially be useful as a marker of immunogenicity of vaccines. However, further investigations should be extended to different cohorts with larger sample size to better understand the functions of these T cells, as well as their relationship with B cells and antibodies.

Dataset Information

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

Publications

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

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