Qualitative Differences in T cell responses to Live, Attenuated and Inactivated Influenza Vaccines

Maryna C Eichelberger

doi:10.4172/2155-9899.s4-002

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.

Highlights

Influenza viruses cause annual epidemics during winter months, with substantial respiratory illness and mortality worldwide, in the elderly and very young [1]
The induction of cellular responses by LAIV is confirmed in clinical studies: for example, increased numbers of influenza-specific CD4+ and CD8+ T cell responses can be measured in young children vaccinated and boosted with LAIV but not trivalent inactivated influenza vaccines (TIV) [17]
The following influenza viruses were grown in 10-day old embryonated chicken eggs: Viruses corresponding to the 2006/07 vaccine: A/New Caledonia/20/99 (H1N1) (A/NC/99), A/ Wisconsin/67/2005 X161B (H3N2) (A/WI/05), B/Malaysia/2506/04 (BM/04), and viruses used for NA inhibition assays: H6N1NC/99, and H6N1WI/05

Summary

Introduction

Influenza viruses cause annual epidemics during winter months, with substantial respiratory illness and mortality worldwide, in the elderly and very young [1]. In April 2009, a swine-origin H1N1 virus emerged in humans that was antigenically distinct from other viruses previously circulating, resulting in efforts to rapidly manufacture and distribute a vaccine with matching HA and NA antigens Both monovalent inactivated and live, attenuated vaccines were licensed and available by October 2009, and this strain was subsequently included as the H1N1 component of seasonal trivalent influenza vaccines. The interactions and soluble factors elicited during initiation of the response are different for TIV and LAIV and would be expected to induce distinct CD4+ T cell types following immunization that may dictate the quality and quantity of the influenza-specific antibody response. The induction of cellular responses by LAIV is confirmed in clinical studies: for example, increased numbers of influenza-specific CD4+ and CD8+ T cell responses can be measured in young children vaccinated and boosted with LAIV but not TIV [17]. Our results show that the cellular responses after vaccination with LAIV and TIV are distinct: a greater number of LAIV recipients had increased IFN-γ secretion, whereas IL-5 secretion was more frequently increased in TIV-immunized adults

Materials and Methods

Results and Discussion

Evaluation of LAIV immunogenicity in adults