Safety and Immunogenicity of M2-Deficient, Single Replication, Live Influenza Vaccine (M2SR) in Adults.

Joseph Eiden,Yoshihiro Kawaoka,Carlos Fierro,Daniel Hoft,Gilad Gordon,Gabriele Neumann,Paul Radspinner,Robert Belshe,Renee Herber,Michael J Moser,Roger Aitchison,Pamuk Bilsel,Harry Greenberg,Yasuko Hatta,Magdalena Tary-Lehmann

doi:10.3390/vaccines9121388

Abstract

M2SR (M2-deficient single replication) is an investigational live intranasal vaccine that protects against multiple influenza A subtypes in influenza-naïve and previously infected ferrets. We conducted a phase 1, first-in-human, randomized, dose-escalation, placebo-controlled study of M2SR safety and immunogenicity. Adult subjects received a single intranasal administration with either placebo or one of three M2SR dose levels (106, 107 or 108 tissue culture infectious dose (TCID50)) expressing hemagglutinin and neuraminidase from A/Brisbane/10/2007 (H3N2) (24 subjects per group). Subjects were evaluated for virus replication, local and systemic reactions, adverse events (AE), and immune responses post-vaccination. Infectious virus was not detected in nasal swabs from vaccinated subjects. At least one AE (most commonly mild nasal rhinorrhea/congestion) was reported among 29%, 58%, and 83% of M2SR subjects administered a low, medium or high dose, respectively, and among 46% of placebo subjects. No subject had fever or a severe reaction to the vaccine. Influenza-specific serum and mucosal antibody responses and B- and T-cell responses were significantly more frequent among vaccinated subjects vs. placebo recipients. The M2SR vaccine was safe and well tolerated and generated dose-dependent durable serum antibody responses against diverse H3N2 influenza strains. M2SR demonstrated a multi-faceted immune response in seronegative and seropositive subjects.

Highlights

Licensee MDPI, Basel, Switzerland.Influenza viruses cause respiratory disease and additional medical complications, resulting in over 200,000 hospitalizations and 12,000 to 61,000 deaths per year in the United States [1]
There is a need for new effective influenza vaccines that induce broader, cross-reactive and durable immune responses
More subjects (46%) had a baseline hemagglutination inhibition (HAI) ≥40 in the high-dose group compared to placebo, low and medium-dose groups (25%, 31%, 33%, respectively), but the differences were not statistically significant

Summary

Introduction

Influenza viruses cause respiratory disease and additional medical complications, resulting in over 200,000 hospitalizations and 12,000 to 61,000 deaths per year in the United States [1]. The CDC recommends seasonal influenza vaccination for all individuals aged 6 months and older. VE against the H3N2 subtype is especially problematic, accounting for higher hospitalization rates and excess mortality compared with H1N1 and influenza B infections [3]. Concerns have been raised regarding waning of protection within the course of a single influenza season [4,5,6,7]. There is a need for new effective influenza vaccines that induce broader, cross-reactive and durable immune responses

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