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Cellular immune responses of older adults to four influenza vaccines: Results of a randomized, controlled comparison.
Hum Vaccin Immunother 2017; 13(9):2048-2057HV

Abstract

Cellular immunity is important for protection against the serious complications of influenza in older adults. As it is unclear if newer influenza vaccines elicit greater cellular responses than standard vaccines, we compared responses to 2 standard and 2 newer licensed trivalent inactivated vaccines (TIVs) in a randomized trial in older adults. Non-frail adults ≥ 65 y old were randomly assigned to receive standard subunit, MF59-adjuvanted subunit, standard split-virus or intradermal split-virus TIV. Peripheral blood mononuclear cells (PBMC) harvested pre- and 3-weeks post-vaccination were stimulated with live A/H3N2 virus. PBMC supernatants were tested for interleukin 10 (IL-10) and interferon gamma (IFN-γ), and lysates for granzyme B (GrB). Flow cytometry identified CD4+ and CD8+ T- cells expressing intracellular IL-2, IL-10, IFN-γ, GrB, or perforin. Differences following immunization were assessed for paired subject samples and among vaccines. 120 seniors participated, 29-31 per group, which were well matched demographically. Virus-stimulated PBMCs were GrB-rich before and after vaccination, with minimal increases evident. Immunization did not increase secretion of IFN-γ or IL-10. However, cytolytic effector T-cells (CD8+GrB+perforin+) increased significantly in percentage post-vaccination in all groups, to similar mean values across groups. CD4+GrB+perforin+ T-cells also increased significantly after each vaccine, to similar mean values among vaccines. Vaccination did not increase the low baseline percentages of CD4+ or CD8+ T-cells expressing IFN-γ, IL-2 or IL-10 . In conclusion, participants had pre-existing cellular immunity to H3N2 virus. All 4 vaccines boosted cellular responses to a similar but limited extent, particularly cytolytic effector CD8+ T-cells associated with clinical protection against influenza.

Authors+Show Affiliations

a Health Sciences North Research Institute , Sudbury , Ontario , Canada.a Health Sciences North Research Institute , Sudbury , Ontario , Canada. b Northern Ontario School of Medicine , Sudbury , Ontario , Canada. c VITALITY Research Center , Vancouver Coastal Health Research Institute , Vancouver , BC , Canada. d Public Health Agency of Canada/Canadian Institutes of Health Research Influenza Research Network (PCIRN), Dalhousie University , Halifax , NS , Canada.e Regulatory Research Division , Biologics and Genetic Therapies Directorate Health Canada , Ottawa , Canada.e Regulatory Research Division , Biologics and Genetic Therapies Directorate Health Canada , Ottawa , Canada.a Health Sciences North Research Institute , Sudbury , Ontario , Canada.d Public Health Agency of Canada/Canadian Institutes of Health Research Influenza Research Network (PCIRN), Dalhousie University , Halifax , NS , Canada. f Vaccine Evaluation Center , University of British Columbia , Vancouver , BC , Canada.d Public Health Agency of Canada/Canadian Institutes of Health Research Influenza Research Network (PCIRN), Dalhousie University , Halifax , NS , Canada. g Canadian Center for Vaccinology , Dalhousie University , Halifax , NS , Canada.d Public Health Agency of Canada/Canadian Institutes of Health Research Influenza Research Network (PCIRN), Dalhousie University , Halifax , NS , Canada. f Vaccine Evaluation Center , University of British Columbia , Vancouver , BC , Canada.

Pub Type(s)

Clinical Trial
Comparative Study
Journal Article
Randomized Controlled Trial
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

28635557

Citation

Kumar, Arun, et al. "Cellular Immune Responses of Older Adults to Four Influenza Vaccines: Results of a Randomized, Controlled Comparison." Human Vaccines & Immunotherapeutics, vol. 13, no. 9, 2017, pp. 2048-2057.
Kumar A, McElhaney JE, Walrond L, et al. Cellular immune responses of older adults to four influenza vaccines: Results of a randomized, controlled comparison. Hum Vaccin Immunother. 2017;13(9):2048-2057.
Kumar, A., McElhaney, J. E., Walrond, L., Cyr, T. D., Merani, S., Kollmann, T. R., ... Scheifele, D. W. (2017). Cellular immune responses of older adults to four influenza vaccines: Results of a randomized, controlled comparison. Human Vaccines & Immunotherapeutics, 13(9), pp. 2048-2057. doi:10.1080/21645515.2017.1337615.
Kumar A, et al. Cellular Immune Responses of Older Adults to Four Influenza Vaccines: Results of a Randomized, Controlled Comparison. Hum Vaccin Immunother. 2017 09 2;13(9):2048-2057. PubMed PMID: 28635557.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Cellular immune responses of older adults to four influenza vaccines: Results of a randomized, controlled comparison. AU - Kumar,Arun, AU - McElhaney,Janet E, AU - Walrond,Lisa, AU - Cyr,Terry D, AU - Merani,Shahzma, AU - Kollmann,Tobias R, AU - Halperin,Scott A, AU - Scheifele,David W, Y1 - 2017/06/21/ PY - 2017/6/22/pubmed PY - 2018/5/15/medline PY - 2017/6/22/entrez KW - adults KW - cellular immunity KW - immune response KW - immunization KW - influenza SP - 2048 EP - 2057 JF - Human vaccines & immunotherapeutics JO - Hum Vaccin Immunother VL - 13 IS - 9 N2 - Cellular immunity is important for protection against the serious complications of influenza in older adults. As it is unclear if newer influenza vaccines elicit greater cellular responses than standard vaccines, we compared responses to 2 standard and 2 newer licensed trivalent inactivated vaccines (TIVs) in a randomized trial in older adults. Non-frail adults ≥ 65 y old were randomly assigned to receive standard subunit, MF59-adjuvanted subunit, standard split-virus or intradermal split-virus TIV. Peripheral blood mononuclear cells (PBMC) harvested pre- and 3-weeks post-vaccination were stimulated with live A/H3N2 virus. PBMC supernatants were tested for interleukin 10 (IL-10) and interferon gamma (IFN-γ), and lysates for granzyme B (GrB). Flow cytometry identified CD4+ and CD8+ T- cells expressing intracellular IL-2, IL-10, IFN-γ, GrB, or perforin. Differences following immunization were assessed for paired subject samples and among vaccines. 120 seniors participated, 29-31 per group, which were well matched demographically. Virus-stimulated PBMCs were GrB-rich before and after vaccination, with minimal increases evident. Immunization did not increase secretion of IFN-γ or IL-10. However, cytolytic effector T-cells (CD8+GrB+perforin+) increased significantly in percentage post-vaccination in all groups, to similar mean values across groups. CD4+GrB+perforin+ T-cells also increased significantly after each vaccine, to similar mean values among vaccines. Vaccination did not increase the low baseline percentages of CD4+ or CD8+ T-cells expressing IFN-γ, IL-2 or IL-10 . In conclusion, participants had pre-existing cellular immunity to H3N2 virus. All 4 vaccines boosted cellular responses to a similar but limited extent, particularly cytolytic effector CD8+ T-cells associated with clinical protection against influenza. SN - 2164-554X UR - https://www.unboundmedicine.com/medline/citation/28635557/Cellular_immune_responses_of_older_adults_to_four_influenza_vaccines:_Results_of_a_randomized_controlled_comparison_ L2 - http://www.tandfonline.com/doi/full/10.1080/21645515.2017.1337615 DB - PRIME DP - Unbound Medicine ER -