Innovative Mucosal Vaccine Formulations Against Influenza A Virus Infections.

Cynthia Calzas,Christophe Chevalier

doi:10.3389/fimmu.2019.01605

Cynthia Calzas, Christophe Chevalier

Open Access

https://doi.org/10.3389/fimmu.2019.01605

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Abstract

Despite efforts made to develop efficient preventive strategies, infections with influenza A viruses (IAV) continue to cause serious clinical and economic problems. Current licensed human vaccines are mainly inactivated whole virus particles or split-virion administered via the parenteral route. These vaccines provide incomplete protection against IAV in high-risk groups and are poorly/not effective against the constant antigenic drift/shift occurring in circulating strains. Advances in mucosal vaccinology and in the understanding of the protective anti-influenza immune mechanisms suggest that intranasal immunization is a promising strategy to fight against IAV. To date, human mucosal anti-influenza vaccines consist of live attenuated strains administered intranasally, which elicit higher local humoral and cellular immune responses than conventional parenteral vaccines. However, because of inconsistent protective efficacy and safety concerns regarding the use of live viral strains, new vaccine candidates are urgently needed. To prime and induce potent and long-lived protective immune responses, mucosal vaccine formulations need to ensure the immunoavailability and the immunostimulating capacity of the vaccine antigen(s) at the mucosal surfaces, while being minimally reactogenic/toxic. The purpose of this review is to compile innovative delivery/adjuvant systems tested for intranasal administration of inactivated influenza vaccines, including micro/nanosized particulate carriers such as lipid-based particles, virus-like particles and polymers associated or not with immunopotentiatory molecules including microorganism-derived toxins, Toll-like receptor ligands and cytokines. The capacity of these vaccines to trigger specific mucosal and systemic humoral and cellular responses against IAV and their (cross)-protective potential are considered.

Highlights

Despite progress in antiviral therapies, influenza viruses remain an important cause of respiratory tract (RT) infections in humans and animals worldwide [1]
In our research group, we have demonstrated that mice intranasally immunized with three repetitions of M2e sequence from a H1N1 virus exposed at the surface of nucleoprotein of the respiratory syncytial virus (NRSV)-virus-like particle (VLP) developed strong local and systemic M2e-specific Ab responses and were successfully protected against an i.n. homologous challenge [147]
Vaccination via the i.n. route has the potential to elicit longlasting and cross-protective humoral and cellular immune responses at the portal of entry of respiratory pathogens

Summary

Introduction

Despite progress in antiviral therapies, influenza viruses remain an important cause of respiratory tract (RT) infections in humans and animals worldwide [1]. Influenza A viruses (IAV), whose natural reservoirs are aquatic birds, can infect a broad spectrum of animal species including humans and poultry. Each segment is associated with the viral nucleoprotein (NP) and the three polymerase components, namely the polymerase basic protein 1 (PB1) and 2 (PB2) and the polymerase acidic protein (PA). These ribonucleoprotein complexes are encapsidated by the matrix protein 1 (M1) beneath an envelope composed of a lipid bilayer derived from the host plasma membrane where are embedded the surface glycoproteins HA, NA and the matrix protein 2 (M2). NA is a tetrameric glycoprotein which enzymatically removes sialic acid residues from the surface of infected cells, allowing the release of budding virions. M2 is a tetrameric protein acting as a protonselective ion channel which triggers the uncoating of the viral

Objectives

Conclusion