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Abstract

Annual epidemics of influenza cause considerable morbidity and mortality. Trivalent inactivated vaccine (TIV) and live, attenuated influenza vaccine (LAIV) are licensed in the United States, and both are effective in preventing disease in persons younger than 49. Serum hemagglutination inhibition (HI) titers correlate with TIV but not LAIV efficacy, suggesting that additional effector mechanisms are induced to the live, attenuated vaccine and play an important role in protection against disease. For this reason there is a need to identify surrogate markers of LAIV efficacy that are easily measured in robust assays. We have compared the immunogenicity of TIV and LAIV in a small clinical study (16 age-matched volunteers in each vaccine group) by measuring serologic responses using traditional HI and NA inhibition assays as well as a sensitive cell-based neutralization assay. In addition, we evaluated cellular responses by measuring the quantity and quality of antigen-specific CD4+ and CD8+ T cells following vaccination. The quality of the CD4+ T cell response was different for each vaccination group, with CD4+ T cell proliferation and increased secretion of IFN-γ characteristic of responses following immunization with LAIV, while antigen-specific T cells that secreted IL-5 were more frequently measured from TIV recipients. Our results suggest that sensitive, serologic assays with broad specificity, together with CD4+ T cell proliferation and IFN-γ secretion provide a more complete measure of the immunogenicity of LAIV in adults, and could be used to enhance the identification of vaccine responders.