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T cell responses are better correlates of vaccine protection in the elderly.

Abstract

It is commonly held that increased risk of influenza in the elderly is due to a decline in the Ab response to influenza vaccination. This study prospectively evaluated the relationship between the development of influenza illness, and serum Ab titers and ex vivo cellular immune responses to influenza vaccination in community dwelling older adults including those with congestive heart failure (CHF). Adults age 60 years and older (90 subjects), and 10 healthy young adult controls received the 2003-04 trivalent inactivated influenza vaccine. Laboratory diagnosed influenza (LDI) was documented in 9 of 90 older adults. Pre- and postvaccination Ab titers did not distinguish between subjects who would subsequently develop influenza illness (LDI subjects) and those who would not (non-LDI subjects). In contrast, PBMC restimulated ex vivo with live influenza virus preparations showed statistically significant differences between LDI and non-LDI subjects. The mean IFN-gamma:IL-10 ratio in influenza A/H3N2-stimulated PBMC was 10-fold lower in LDI vs non-LDI subjects. Pre-and postvaccination granzyme B levels were significantly lower in CHF subjects with LDI compared with subjects without LDI. In non-CHF subjects with LDI, granzyme B levels increased to high levels at the time of influenza infection. In conclusion, measures of the ex vivo cellular immune response to influenza are correlated with protection against influenza while serum Ab responses may be limited as a sole measure of vaccine efficacy in older people. Ex vivo measures of the cell-mediated immune response should be incorporated into evaluation of new vaccines for older adults.

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  • Authors+Show Affiliations

    ,

    Center for Immunotherapy of Cancer and Infectious Diseases, MC1601, University of Connecticut Health Center, 263 Farmington Avenue, Farmington, CT 06030-1601, USA. jmcelhaney@uchc.edu

    , , , , , , ,

    Source

    MeSH

    Adult
    Aged
    Antibodies, Viral
    Cells, Cultured
    Granzymes
    Humans
    Influenza A Virus, H1N1 Subtype
    Influenza A Virus, H3N2 Subtype
    Influenza Vaccines
    Influenza, Human
    Interferon-gamma
    Interleukin-10
    Middle Aged
    Prospective Studies
    Serine Endopeptidases
    T-Lymphocytes

    Pub Type(s)

    Comparative Study
    Journal Article
    Research Support, N.I.H., Extramural
    Research Support, Non-U.S. Gov't

    Language

    eng

    PubMed ID

    16670345

    Citation

    McElhaney, Janet E., et al. "T Cell Responses Are Better Correlates of Vaccine Protection in the Elderly." Journal of Immunology (Baltimore, Md. : 1950), vol. 176, no. 10, 2006, pp. 6333-9.
    McElhaney JE, Xie D, Hager WD, et al. T cell responses are better correlates of vaccine protection in the elderly. J Immunol. 2006;176(10):6333-9.
    McElhaney, J. E., Xie, D., Hager, W. D., Barry, M. B., Wang, Y., Kleppinger, A., ... Bleackley, R. C. (2006). T cell responses are better correlates of vaccine protection in the elderly. Journal of Immunology (Baltimore, Md. : 1950), 176(10), pp. 6333-9.
    McElhaney JE, et al. T Cell Responses Are Better Correlates of Vaccine Protection in the Elderly. J Immunol. 2006 May 15;176(10):6333-9. PubMed PMID: 16670345.
    * Article titles in AMA citation format should be in sentence-case
    TY - JOUR T1 - T cell responses are better correlates of vaccine protection in the elderly. AU - McElhaney,Janet E, AU - Xie,Dongxu, AU - Hager,W David, AU - Barry,Mary Beth, AU - Wang,Yazhen, AU - Kleppinger,Alison, AU - Ewen,Catherine, AU - Kane,Kevin P, AU - Bleackley,R Chris, PY - 2006/5/4/pubmed PY - 2006/6/23/medline PY - 2006/5/4/entrez SP - 6333 EP - 9 JF - Journal of immunology (Baltimore, Md. : 1950) JO - J. Immunol. VL - 176 IS - 10 N2 - It is commonly held that increased risk of influenza in the elderly is due to a decline in the Ab response to influenza vaccination. This study prospectively evaluated the relationship between the development of influenza illness, and serum Ab titers and ex vivo cellular immune responses to influenza vaccination in community dwelling older adults including those with congestive heart failure (CHF). Adults age 60 years and older (90 subjects), and 10 healthy young adult controls received the 2003-04 trivalent inactivated influenza vaccine. Laboratory diagnosed influenza (LDI) was documented in 9 of 90 older adults. Pre- and postvaccination Ab titers did not distinguish between subjects who would subsequently develop influenza illness (LDI subjects) and those who would not (non-LDI subjects). In contrast, PBMC restimulated ex vivo with live influenza virus preparations showed statistically significant differences between LDI and non-LDI subjects. The mean IFN-gamma:IL-10 ratio in influenza A/H3N2-stimulated PBMC was 10-fold lower in LDI vs non-LDI subjects. Pre-and postvaccination granzyme B levels were significantly lower in CHF subjects with LDI compared with subjects without LDI. In non-CHF subjects with LDI, granzyme B levels increased to high levels at the time of influenza infection. In conclusion, measures of the ex vivo cellular immune response to influenza are correlated with protection against influenza while serum Ab responses may be limited as a sole measure of vaccine efficacy in older people. Ex vivo measures of the cell-mediated immune response should be incorporated into evaluation of new vaccines for older adults. SN - 0022-1767 UR - https://www.unboundmedicine.com/medline/citation/16670345/T_cell_responses_are_better_correlates_of_vaccine_protection_in_the_elderly_ L2 - http://www.jimmunol.org/cgi/pmidlookup?view=long&pmid=16670345 DB - PRIME DP - Unbound Medicine ER -