4.7 Article

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

Journal

BIOMEDICINES
Volume 9, Issue 2, Pages -

Publisher

MDPI
DOI: 10.3390/biomedicines9020133

Keywords

influenza; universal influenza vaccine; live attenuated influenza vaccine; M2e antigen; recombinant influenza virus; cross-protection; mouse model; CDC; ADCC; IgG

Funding

  1. Russian Science Foundation [19-15-00015]
  2. National Institutes of Health/National Institute of Allergy and Infectious Diseases (NIH/NIAID) [AI1093772, AI147042]
  3. Russian Science Foundation [19-15-00015] Funding Source: Russian Science Foundation

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Influenza viruses remain a serious public health problem, with seasonal influenza vaccines showing low effectiveness against drifted and new viruses. Research is ongoing to develop strategies to elicit immune responses against conserved parts of influenza virus proteins. A study constructing a universal live attenuated influenza vaccine (LAIV) candidate with enhanced breadth of protection showed promising results in increasing protection against heterosubtypic challenge viruses compared to classical LAIV. Further investigation in pre-clinical and clinical trials is warranted.
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.

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