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Cellular immune responses of older adults to four influenza vaccines: Results of a randomized, controlled comparison.

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-?), and lysates for granzyme B (GrB). Flow cytometry identified CD4+ and CD8+ T- cells expressing intracellular IL-2, IL-10, IFN-?, 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-? 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-?, 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.

SUBMITTER: Kumar A

PROVIDER: S-EPMC5612046 | biostudies-literature | 2017 Sep

REPOSITORIES: biostudies-literature

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Cellular immune responses of older adults to four influenza vaccines: Results of a randomized, controlled comparison.

Kumar Arun A McElhaney Janet E JE Walrond Lisa L Cyr Terry D TD Merani Shahzma S Kollmann Tobias R TR Halperin Scott A SA Scheifele David W DW

Human vaccines & immunotherapeutics 20170621 9

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 ...[more]

PMID: 28635557

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Project description:IntroductionTrivalent influenza vaccines (TIVs) are currently reimbursed for subjects aged ≥ 65 years and children between 6 and 59 months of age under a national immunization program in South Korea. Quadrivalent influenza vaccines (QIVs) are expected to address the potential problem of influenza B-lineage mismatch for TIVs.ObjectiveThe objective of this analysis was to compare the cost effectiveness of QIV versus TIV in children aged 6-59 months and older adults ≥ 65 years of age in South Korea.MethodsA 1-year static population model was employed to compare the costs and outcomes of a QIV vaccination program compared with TIV in children aged 6-59 months and older adults ≥ 65 years of age in South Korea. Influenza-related parameters (probabilities, health resource use, and costs) were derived from an analysis of the National Health Insurance System claims database between 2010 and 2013 under a broad and narrow set of International Classification of Diseases, Tenth Revision (ICD-10) codes used to identify influenza. Other inputs were extracted from published literature. Incremental cost-effectiveness ratios (2016 South Korean Won [KRW] per quality-adjusted life-year [QALY] gained) were estimated using a 'limited' societal perspective as per the Korean pharmacoeconomic guidelines. QALYs lost due to premature mortality were discounted at 5% annually.ResultsFor both age groups combined, under the narrow definition of influenza, QIV is expected to prevent nearly 16,000 (2923 in children and 13,011 in older adults) medically attended influenza cases, nearly 8000 (672 in children, 7048 in older adults) cases of complications, and over 230 (0 in children, 238 in older adults) deaths annually compared with TIV. The impact of using QIV versus TIV in this setting translates into savings of KRW 24 billion (KRW 0.6 billion in children, KRW 23.4 billion in older adults) in annual medical costs, and over 2100 (18 in children, 2084 in older adults) QALYs. Under the broad definition, the corresponding results are over 190,000 (50,697 in children, 140,644 in older adults) influenza cases, over 37,000 (12,623 in children, 24,526 in older adults) complications, 270 deaths (0 in children, 270 in older adults), KRW 94.22 billion (KRW 16 billion in children, KRW 78.2 billion in older adults), and over 3500 QALYs saved (316 in children, 3260 in older adults).ConclusionThe use of QIV over TIV was estimated to not be cost effective in children 6-59 months of age, but cost saving in older adults, using the narrow definition of influenza; however, QIV use was cost saving in both age groups using the broad definition. QIV is expected to yield more benefits in older adults ≥ 65 years of age than in children aged 6-59 months due to higher influenza-related mortality and costs among the older adults. Further analyses considering the indirect effects of influenza vaccination in children are required.

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Cellular immune responses of older adults to four influenza vaccines: Results of a randomized, controlled comparison.

Publications

Cellular immune responses of older adults to four influenza vaccines: Results of a randomized, controlled comparison.

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