Superior in vitro stimulation of human CD8+ T-cells by whole virus versus split virus influenza vaccines.

Benedict R Halbroth,Hans Christian Probst,Eva Distler,Eva M Wagner,Anita Karner,Udo F Hartwig,Katharina Landfester,Alexander Heil,Otfried Kistner,Martin Dass,Wolfgang Herr,Gerald Aichinger,Dennis Strand,Bodo Plachter,John Stambas

doi:10.1371/journal.pone.0103392

Abstract

Pandemic and seasonal influenza viruses cause considerable morbidity and mortality in the general human population. Protection from severe disease may result from vaccines that activate antigen-presenting DC for effective stimulation of influenza-specific memory T cells. Special attention is paid to vaccine-induced CD8+ T-cell responses, because they are mainly directed against conserved internal influenza proteins thereby presumably mediating cross-protection against circulating seasonal as well as emerging pandemic virus strains. Our study showed that influenza whole virus vaccines of major seasonal A and B strains activated DC more efficiently than those of pandemic swine-origin H1N1 and pandemic-like avian H5N1 strains. In contrast, influenza split virus vaccines had a low ability to activate DC, regardless which strain was investigated. We also observed that whole virus vaccines stimulated virus-specific CD8+ memory T cells much stronger compared to split virus counterparts, whereas both vaccine formats activated CD4+ Th cell responses similarly. Moreover, our data showed that whole virus vaccine material is delivered into the cytosolic pathway of DC for effective activation of virus-specific CD8+ T cells. We conclude that vaccines against seasonal and pandemic (-like) influenza strains that aim to stimulate cross-reacting CD8+ T cells should include whole virus rather than split virus formulations.

Highlights

Seasonal influenza A and B viruses cause recurrent epidemics typically during the cold months, resulting in hundreds of thousands of deaths every year
Whole virus vaccines were analyzed for the ability to induce maturation in monocyte-derived immature DC of healthy individuals
Vaccines were available from seasonal strains A/ H1N1-Brisbane, A/H3N2-Uruguay, and B/Brisbane, as well as from recent pandemic-like avian and pandemic swine-origin strains A/H5N1-Indonesia, A/H5N1-Vietnam, and A/H1N1California, respectively (Table 1)

Summary

Introduction

Seasonal influenza A and B viruses cause recurrent epidemics typically during the cold months, resulting in hundreds of thousands of deaths every year. The swine-origin H1N1 virus, which has provoked the latest influenza pandemic in 2009, and the pandemic-like H5N1 virus, which was recently reported to require as few as 5 amino acid substitutions to become airborne transmissible between ferrets, create common fears of a pandemic with a highly pathogenic influenza virus [1,2,3]. Strategies to overcome this threat include the development of influenza vaccines designed to elicit protective immunity against heterologous influenza virus strains [4,5]. There is accumulating interest in whole virus vaccination strategies that elicit influenzaspecific CD8+ CTL responses in humans and the question if such responses are directed against seasonal and recently circulating pandemic (-like) influenza strains

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Results

Conclusion