Abstract

Influenza virus is a source of significant health and economic burden from yearly epidemics and sporadic pandemics. Given the potential for the emerging H7N9 influenza virus to cause severe respiratory infections and the lack of exposure to H7 and N9 influenza viruses in the human population, we aimed to quantify the H7N9 cross-reactive memory T cell reservoir in humans and mice previously exposed to common circulating influenza viruses. We identified significant cross-reactive T cell populations in humans and mice; we also found that cross-reactive memory T cells afforded heterosubtypic protection by reducing morbidity and mortality upon lethal H7N9 challenge. In context with our observation that PR8-primed mice have limited humoral cross-reactivity with H7N9, our data suggest protection from H7N9 challenge is indeed mediated by cross-reactive T cell populations established upon previous priming with another influenza virus. Thus, pre-existing cross-reactive memory T cells may limit disease severity in the event of an H7N9 influenza virus pandemic.

Highlights

  • Influenza viruses are a primary cause of severe respiratory tract infections worldwide

  • IFN-γ responses to inactivated H7N9 influenza virus stimulations were directly compared to paired samples that were either left unstimulated or were stimulated with inactivated Sendai virus as a negative control, as Sendai virus does not share any cross-reactive T cell epitopes with influenza virus

  • For mice infected with each of the three priming conditions (PR8, X31, pandemic A/California/09 H1N1 (pH1N1)), there was a significant percentage of CD8 (Fig. 1B, top) and CD4 (Fig. 1B, bottom) T cells cross-reactive to H7N9 as compared to matched unstimulated or Sendai virus stimulated samples

Read more

Summary

Introduction

Influenza viruses are a primary cause of severe respiratory tract infections worldwide. In February of 2013, an H7N9 influenza A virus (H7N9) of avian origin was laboratory confirmed in four human cases, resulting in three deaths [1]. Clinical symptoms in these cases included fever and intractable pneumonia unresponsive to antibiotics, which progressively extended to more severe systemic complications [2]. The majority of human cases have been associated with either direct contact with avian sources or poultry markets, and transmission studies on H7N9 in guinea pigs and ferrets have demonstrated a limited.

Objectives
Results
Conclusion
Full Text
Published version (Free)

Talk to us

Join us for a 30 min session where you can share your feedback and ask us any queries you have

Schedule a call