A Strategy to Elicit M2e-Specific Antibodies Using a Recombinant H7N9 Live Attenuated Influenza Vaccine Expressing Multiple M2e Tandem Repeats.

Sang-Moo Kang,Larisa Rudenko,Tatiana Kotomina,Min-Chul Kim,Ki-Hye Kim,Irina Isakova-Sivak,Noopur Bhatnagar,Victoria Matyushenko,Daria Mezhenskaya

doi:10.3390/biomedicines9020133

Abstract

Influenza viruses remain a serious public health problem. Vaccination is the most effective way to prevent the disease; however, seasonal influenza vaccines demonstrate low or no effectiveness against antigenically drifted and newly emerged influenza viruses. Different strategies of eliciting immune responses against conserved parts of various influenza virus proteins are being developed worldwide. We constructed a universal live attenuated influenza vaccine (LAIV) candidate with enhanced breadth of protection by modifying H7N9 LAIV by incorporating four epitopes of M2 protein extracellular part into its hemagglutinin molecule. The new recombinant H7N9+4M2e vaccine induced anti-M2e antibody responses and demonstrated increased protection against heterosubtypic challenge viruses in direct and serum passive protection studies, compared to the classical H7N9 LAIV. The results of our study suggest that the H7N9+4M2e warrants further investigation in pre-clinical and phase 1 clinical trials.

Highlights

Despite the ongoing COVID-19 pandemic, influenza remains a serious public health concern, especially in light of a number of documented cases of SARS-CoV-2 and influenzaA co-infections in humans [1,2,3,4]
We showed that the H7N9+4M2e recombinant virus was genetically stable, i.e., the insert was preserved after serial passages of the viruses in eggs and no mutations have been detected in the viral genome by passage E10
Comparison of H7N9+4M2e chimeric virus with H7N9 classical counterpart revealed the absence of any negative effect of the 4M2e insert on the replicative characteristics of the H7N9 live attenuated influenza vaccine (LAIV) virus (Figure 3B,C). These results suggest that the insertion of 4M2e epitopes into the HA molecule did not interfere with HA functional activity or alter major LAIV properties

Summary

Introduction

Despite the ongoing COVID-19 pandemic, influenza remains a serious public health concern, especially in light of a number of documented cases of SARS-CoV-2 and influenzaA co-infections in humans [1,2,3,4]. The World Health Organization (WHO) estimated that seasonal influenza can cause up to 645,832 deaths around the world annually [5]. New antigenic variants of influenza viruses periodically arise in circulation causing devastating pandemics [6]. Vaccination is considered the first line of defense against influenza, but the ever-changing nature of influenza viruses result in ineffectiveness of vaccination after a single season or against new pandemic strains. Among several conserved influenza A viral proteins and epitopes, the ectodomain of matrix 2 protein (M2e) is a promising target for universal influenza vaccine design [9]. This domain is highly conserved among influenza

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