Abstract

BACKGROUND: Older adults are at high-risk of influenza disease, but generally respond poorly to vaccination. Antibody-dependent cellular cytotoxicity (ADCC) may be an important component of protection against influenza infection. An improved understanding of the ADCC response to influenza vaccination in older adults is required.

METHODS: We studied sera samples from three groups of subjects aged 65 years (n=16-17/group) receiving the 2008/2009 seasonal trivalent influenza vaccine (TIV). Subjects had minimal pre-existing hemagglutination inhibiting (HAI) antibodies and TIV induced either no, low or high HAI responses. Serum ADCC activity was analyzed using Fc receptor cross-linking, NK cell activation and influenza-infected cell killing.

RESULTS: Most subjects from TIV non-responder, low-responder and high-responder groups had detectable ADCC antibodies pre-vaccination, but baseline ADCC was not predictive of HAI vaccine responsiveness. Interestingly, ADCC and HAI responses tracked closely across all groups, against all three TIV HAs and in all ADCC assays tested.

CONCLUSIONS: Older adults commonly have pre-existing ADCC antibodies in the absence of high HAI titres to circulating influenza strains. In older vaccinees, the ADCC response mirrored HAI antibodies and was readily detectable despite high post-vaccination HAI titres. There is a need for alternate measures of vaccine responsiveness and improved vaccinations in this at-risk group.

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