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Center for Infectious Disease and Vaccine Research, University of Massachusetts Medical School, Worcester, MA 01655, United States.
Vaccine (Impact Factor: 3.62). 05/2008; 26(16):1990-8. DOI: 10.1016/j.vaccine.2008.02.024
Source: PubMed


Thirty adults were tested for humoral and cellular immune responses following immunization with the trivalent inactivated influenza vaccine. Modest but significant inverse correlations between the baseline and the fold changes in the number of IFNgamma-producing cells and the levels of neutralizing antibodies were observed. Specific increases in proliferative responses in the CD8 CD45RA+ population were noted after vaccination. Minimal correlations between neutralizing antibody titers and the number of IFNgamma-producing cells in terms of prevaccination levels or fold increases were observed. These results show specific increases in a CD8 T cell subset and discordant T and B responses induced by the trivalent inactivated influenza vaccine.

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Available from: Pamela Pazoles, Oct 09, 2015
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    • "Although CD4 T cells are important for generating NAb, there is some debate as to whether CD4 T cells and antibodies correlate following influenza vaccination [10,28,29]. Moreover, the role of pre-existing Ab in vaccine-induced CD4 T cell expansion is not well defined. "
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    ABSTRACT: Current yearly influenza virus vaccines induce strain-specific neutralizing antibody (NAb) responses providing protective immunity to closely matched viruses. However, these vaccines are often poorly effective in high-risk groups such as the elderly and challenges exist in predicting yearly or emerging pandemic influenza virus strains to include in the vaccines. Thus, there has been considerable emphasis on understanding broadly protective immunological mechanisms for influenza virus. Recent studies have implicated memory CD4 T cells in heterotypic immunity in animal models and in human challenge studies. Here we examined how influenza virus vaccination boosted CD4 T cell responses in younger versus aged humans. Our results demonstrate that while the magnitude of the vaccine-induced CD4 T cell response and number of subjects responding on day 7 did not differ between younger and aged subjects, fewer aged subjects had peak responses on day 14. While CD4 T cell responses were inefficiently boosted against NA, both HA and especially nucleocaspid protein- and matrix-(NP+M) specific responses were robustly boosted. Pre-existing CD4 T cell responses were associated with more robust responses to influenza virus NP+M, but not H1 or H3. Finally pre-existing strain-specific NAb decreased the boosting of CD4 T cell responses. Thus, accumulation of pre-existing influenza virus-specific immunity in the form of NAb and cross-reactive T cells to conserved virus proteins (e.g. NP and M) over a lifetime of exposure to infection and vaccination may influence vaccine-induced CD4 T cell responses in the aged.
    PLoS ONE 10/2013; 8(10):e77164. DOI:10.1371/journal.pone.0077164 · 3.23 Impact Factor
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    • "The phenotype or activation state of T cells is important for protection against influenza such that naïve cells are less able to protect than activated or memory cells against a lethal influenza infection [10], [11]. Activated influenza specific T cells have been shown to be associated with protection against influenza in human studies [12], [13], [14], [15] but no study of surface or intracellular phenotype was done. "
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    ABSTRACT: Current influenza vaccines stimulate neutralising antibody to the haemagglutinin antigen but as there is antigenic drift in HA it is difficult to prepare a vaccine in advance against an emergent strain. A potential strategy is to induce CD8(+) and CD4(+) T cells that recognize epitopes within internal proteins that are less subject to antigenic drift. Augmenting humoral responses to HA with T cell responses to more conserved antigens may result in a more broadly protective vaccine. In this study, we evaluate the quality of influenza specific T cell responses in a clinical trial using MVA-NP+M1 vaccination followed by influenza virus challenge. In vaccinated volunteers, the expression of Granzyme A, Perforin and CD57 on influenza HLA A*02 M158-66 antigen specific cells was higher than non-vaccinated volunteers before and after challenge despite a similar frequency of antigen specific cells. BCL2 expression was lower in vaccinated volunteers. These data indicate that antigen specific T cells are a useful additional measure for use in human vaccination or immunization studies.
    PLoS ONE 05/2013; 8(5):e62778. DOI:10.1371/journal.pone.0062778 · 3.23 Impact Factor
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    • "A number of studies have attempted to identify correlates of protection to distinguish individuals who are at greater risk of acquiring a severe influenza infection. Studies have confirmed that antibody titers and T cell responses post-vaccination with TIV do not correlate with one another [24], [25]. Although some literature has suggested that the cell-mediated compartment is less functional in older donors, these studies were done on bulk peripheral blood mononuclear cells (PBMC) and did not definitively identify a T cell population responsible for producing the protective or detrimental factors [25], [26]. "
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    ABSTRACT: T cells specific for persistent pathogens accumulate with age and express markers of immune senescence. In contrast, much less is known about the state of T cell memory for acutely infecting pathogens. Here we examined T cell responses to influenza in human peripheral blood mononuclear cells from older (>64) and younger (<40) donors using whole virus restimulation with influenza A (A/PR8/34) ex vivo. Although most donors had pre-existing influenza reactive T cells as measured by IFNγ production, older donors had smaller populations of influenza-responsive T cells than young controls and had lost a significant proportion of their CD45RA-negative functional memory population. Despite this apparent dysfunction in a proportion of the older T cells, both old and young donors' T cells from 2008 could respond to A/California/07/2009 ex vivo. For HLA-A2+ donors, MHC tetramer staining showed that a higher proportion of influenza-specific memory CD8 T cells from the 65+ group co-express the markers killer cell lectin-like receptor G1 (KLRG1) and CD57 compared to their younger counterparts. These markers have previously been associated with a late differentiation state or immune senescence. Thus, memory CD8 T cells to an acutely infecting pathogen show signs of advanced differentiation and functional deterioration with age. There was a significant negative correlation between the frequency of KLRG1(+)CD57(+) influenza M1-specific CD8 T cells pre-vaccination and the ability to make antibodies in response to vaccination with seasonal trivalent inactivated vaccine, whereas no such trend was observed when the total CD8(+)KLRG1(+)CD57(+) population was analyzed. These results suggest that the state of the influenza-specific memory CD8 T cells may be a predictive indicator of a vaccine responsive healthy immune system in old age.
    PLoS ONE 08/2011; 6(8):e23698. DOI:10.1371/journal.pone.0023698 · 3.23 Impact Factor
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