Modulation of Immune Responses to Influenza A Virus Vaccines by Natural Killer T Cells.

John P Driver,Jürgen A Richt,Darling Melany De Carvalho Madrid,Weihong Gu,Bianca L Artiaga

doi:10.3389/fimmu.2020.02172

John P Driver, Jürgen A Richt + Show 3 more

Open Access

https://doi.org/10.3389/fimmu.2020.02172

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Abstract

Influenza A viruses (IAVs) circulate widely among different mammalian and avian hosts and sometimes give rise to zoonotic infections. Vaccination is a mainstay of IAV prevention and control. However, the efficacy of IAV vaccines is often suboptimal because of insufficient cross-protection among different IAV genotypes and subtypes as well as the inability to keep up with the rapid molecular evolution of IAV strains. Much attention is focused on improving IAV vaccine efficiency using adjuvants, which are substances that can modulate and enhance immune responses to co-administered antigens. The current review is focused on a non-traditional approach of adjuvanting IAV vaccines by therapeutically targeting the immunomodulatory functions of a rare population of innate-like T lymphocytes called invariant natural killer T (iNKT) cells. These cells bridge the innate and adaptive immune systems and are capable of stimulating a wide array of immune cells that enhance vaccine-mediated immune responses. Here we discuss the factors that influence the adjuvant effects of iNKT cells for influenza vaccines as well as the obstacles that must be overcome before this novel adjuvant approach can be considered for human or veterinary use.

Highlights

Influenza A viruses (IAVs) are a genetically diverse group of segmented RNA viruses capable of infecting birds and mammals, including swine, bats, and humans [1,2,3]
We summarize the current knowledge about therapeutically harnessing invariant natural killer T (iNKT) cell activities to improve IAV vaccines in mice and other animal models
Ko et al were the first group to explore adjuvanting IAV vaccines with iNKT cell agonists [26]. They reported that BALB/c mice intranasally co-administered with three doses (1 week apart) of α-GalCer and HA antigen derived from the mouse-adapted A/PR/8/34 (PR8, H1N1) IAV were much better protected from a lethal dose of the homologous virus than mice immunized with vaccine alone. α-GalCer induced greater levels of mucosal and systemic IgA and IgG antibodies

Summary

Introduction

Influenza A viruses (IAVs) are a genetically diverse group of segmented RNA viruses capable of infecting birds and mammals, including swine, bats, and humans [1,2,3]. They reported that BALB/c mice intranasally co-administered with three doses (1 week apart) of α-GalCer and HA antigen derived from the mouse-adapted A/PR/8/34 (PR8, H1N1) IAV were much better protected from a lethal dose of the homologous virus than mice immunized with vaccine alone.

Results

Conclusion