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Age dependent differences in the kinetics of ?? T cells after influenza vaccination.

ABSTRACT: Immunosenescence is a hallmark of the aging immune system and is considered the main cause of a reduced vaccine efficacy in the elderly. Although ?? T cells can become activated by recombinant influenza hemagglutinin, their age-related immunocompetence during a virus-induced immune response has so far not been investigated. In this study we evaluate the kinetics of ?? T cells after vaccination with the trivalent 2011/2012 northern hemisphere seasonal influenza vaccine. We applied multi-parametric flow cytometry to a cohort of 21 young (19-30 years) and 23 elderly (53-67 years) healthy individuals. Activated and proliferating ?? T cells, as identified by CD38 and Ki67 expression, were quantified on the days 0, 3, 7, 10, 14, 17, and 21. We observed a significantly lower number of activated and proliferating ?? T cells at baseline and following vaccination in elderly as compared to young individuals. The kinetics changes of activated ?? T cells were much stronger in the young, while corresponding changes in the elderly occurred slower. In addition, we observed an association between day 21 HAI titers of influenza A and the frequencies of Ki67+ ?? T cells at day 7 in the young. In conclusion, aging induces alterations of the ?? T cell response that might have negative implications for vaccination efficacy.

SUBMITTER: Stervbo U

PROVIDER: S-EPMC5507438 | biostudies-literature | 2017

REPOSITORIES: biostudies-literature

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Age dependent differences in the kinetics of γδ T cells after influenza vaccination.

Stervbo Ulrik U Pohlmann Dominika D Baron Udo U Bozzetti Cecilia C Jürchott Karsten K Mälzer Julia Nora JN Nienen Mikalai M Olek Sven S Roch Toralf T Schulz Axel Ronald AR Warth Sarah S Neumann Avidan A Thiel Andreas A Grützkau Andreas A Babel Nina N

PloS one 20170711 7

Immunosenescence is a hallmark of the aging immune system and is considered the main cause of a reduced vaccine efficacy in the elderly. Although γδ T cells can become activated by recombinant influenza hemagglutinin, their age-related immunocompetence during a virus-induced immune response has so far not been investigated. In this study we evaluate the kinetics of γδ T cells after vaccination with the trivalent 2011/2012 northern hemisphere seasonal influenza vaccine. We applied multi-parametri ...[more]

PMID: 28700738

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Project description:The strength and breadth of an individual's antibody repertoire is an important predictor of their response to influenza infection or vaccination. Although progress has been made in understanding qualitatively how repeated exposures shape the antibody mediated immune response, quantitative understanding remains limited. We developed a set of mathematical models describing short-term antibody kinetics following influenza infection or vaccination and fit them to haemagglutination inhibition (HI) titres from 5 groups of ferrets which were exposed to different combinations of trivalent inactivated influenza vaccine (TIV with or without adjuvant), A/H3N2 priming inoculation and post-vaccination A/H1N1 inoculation. We fit models with various immunological mechanisms that have been empirically observed but have not previously been included in mathematical models of antibody landscapes, including: titre ceiling effects, antigenic seniority and exposure-type specific cross reactivity. Based on the parameter estimates of the best supported models, we describe a number of key immunological features. We found quantifiable differences in the degree of homologous and cross-reactive antibody boosting elicited by different exposure types. Infection and adjuvanted vaccination generally resulted in strong, broadly reactive responses whereas unadjuvanted vaccination resulted in a weak, narrow response. We found that the order of exposure mattered: priming with A/H3N2 improved subsequent vaccine response, and the second dose of adjuvanted vaccination resulted in substantially greater antibody boosting than the first. Either antigenic seniority or a titre ceiling effect were included in the two best fitting models, suggesting a role for a mechanism describing diminishing antibody boosting with repeated exposures. Although there was considerable uncertainty in our estimates of antibody waning parameters, our results suggest that both short and long term waning were present and would be identifiable with a larger set of experiments. These results highlight the potential use of repeat exposure animal models in revealing short-term, strain-specific immune dynamics of influenza.

Project description:BackgroundThe unpredictable nature of the potentially devastating impact of 2009 pH1N1 influenza pandemic highlights the need for pandemic preparedness planning, where modeling studies could be most useful for simulations of possible future scenarios.MethodsA compartmental model with pre-symptomatic and asymptomatic influenza infections is proposed which incorporates age groups as well as intervention measures such as age-specific vaccination, in order to study spread of influenza in a community.ResultsWe derive the basic reproduction number and other effective reproduction numbers under various intervention measures. For illustration, we make use of the Pneumonia and Influenza (P&I) mortality data and vaccination data of the very young (age 0-2) and the very old (age > 64) during 2004-2005 Taiwan winter influenza season to fit our model and to compute the relevant reproduction numbers. The reproduction number for this winter flu season is estimated to be slightly above one (approximately 1.0001).ConclusionsComparatively large errors in fitting the P&I mortality data of the elderly (> 64) were observed shortly after winter school closings in January, which may indicate the impact of younger, more active age groups transmitting influenza to other age groups outside of the school settings; in particular, to the elderly in the households. Pre-symptomatic infections seemed to have little effect on the model fit, while asymptomatic infection by asymptomatic infectives has a more pronounced impact on the model fit for the elderly mortality, perhaps indicating a larger role in disease transmission by asymptomatic infection. Simulations indicate that the impact of vaccination on the disease incidence might not be fully revealed in the change (or the lack thereof) in the effective reproduction number with interventions, but could still be substantial. The estimated per contact transmission probability for susceptible elderly is significantly higher than that of any other age group, perhaps highlighting the vulnerability of the elderly due to close contacts with their caretakers from other age groups. The relative impact of targeting the very young and the very old for vaccination was weakened by their relative inactivity, thus giving evidence of the lack of impact of vaccinating these two groups on the overall transmissibility of the disease in the community. This further underscores the need for morbidity-based strategy to prevent elderly mortality.

Dataset Information

Age dependent differences in the kinetics of ?? T cells after influenza vaccination.

Publications

Age dependent differences in the kinetics of γδ T cells after influenza vaccination.

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