Enhanced cross protection by hetero prime-boost vaccination with recombinant influenza viruses containing chimeric hemagglutinin-M2e epitopes

Bo Ryoung Park; Jeeva Subbiah; Ki-Hye Kim; Young-Man Kwon; Judy Oh; Min-Chul Kim; Chong-Hyun Shin; Baik Lin Seong; Sang-Moo Kang

doi:10.1016/j.virol.2021.12.003

Enhanced cross protection by hetero prime-boost vaccination with recombinant influenza viruses containing chimeric hemagglutinin-M2e epitopes

Virology. 2022 Jan:566:143-152. doi: 10.1016/j.virol.2021.12.003. Epub 2021 Dec 10.

Authors

Bo Ryoung Park¹, Jeeva Subbiah¹, Ki-Hye Kim¹, Young-Man Kwon¹, Judy Oh¹, Min-Chul Kim², Chong-Hyun Shin¹, Baik Lin Seong³, Sang-Moo Kang⁴

Affiliations

¹ Institute for Biomedical Sciences, Georgia State University, Atlanta, GA, 30303, USA.
² Institute for Biomedical Sciences, Georgia State University, Atlanta, GA, 30303, USA; CARESIDE Co., Ltd., Seongnam, Gyeonggi-do, Republic of Korea.
³ Department of Microbiology, College of Medicine, Yonsei University, 50 Yonsei-ro, Seodaemun-gu, Seoul, 03722, Republic of Korea; Vaccine Innovative Technology ALliance (VITAL)-Korea, Yonsei University, 50 Yonsei-ro, Seodaemun-gu, Seoul, 03722, Republic of Korea.
⁴ Institute for Biomedical Sciences, Georgia State University, Atlanta, GA, 30303, USA. Electronic address: [email protected].

Abstract

Annual repeat influenza vaccination raises concerns about protective efficacy against mismatched viruses. We investigated the impact of heterologous prime-boost vaccination on inducing cross protection by designing recombinant influenza viruses with chimeric hemagglutinin (HA) carrying M2 extracellular domains (M2e-HA). Heterologous prime-boost vaccination of C57BL/6 mice with M2e-HA chimeric virus more effectively induced M2e and HA stalk specific IgG antibodies correlating with cross protection than homologous prime-boost vaccination. Induction of M2e and HA stalk specific IgG antibodies was compromised in 1-year old mice, indicating significant aging effects on priming subdominant M2e and HA stalk IgG antibody responses. This study demonstrates that a heterologous prime-boost strategy with recombinant influenza virus expressing extra M2e epitopes provides more effective cross protection than homologous vaccination.

Keywords: Cross protection; Live attenuated virus; M2e; Recombinant influenza virus.

Publication types

Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

MeSH terms

Age Factors
Aging / genetics
Aging / immunology*
Animals
Antibodies, Viral / biosynthesis*
Antigens, Viral / genetics
Antigens, Viral / immunology
Cross Protection
Female
Hemagglutinin Glycoproteins, Influenza Virus / genetics*
Hemagglutinin Glycoproteins, Influenza Virus / immunology
Humans
Immunization, Secondary / methods
Immunogenicity, Vaccine
Immunoglobulin G / biosynthesis*
Influenza A Virus, H1N1 Subtype / immunology
Influenza A Virus, H1N1 Subtype / pathogenicity
Influenza A Virus, H3N2 Subtype / immunology
Influenza A Virus, H3N2 Subtype / pathogenicity
Influenza Vaccines / administration & dosage
Influenza Vaccines / biosynthesis
Influenza Vaccines / genetics*
Influenza, Human / immunology
Influenza, Human / prevention & control*
Influenza, Human / virology
Mice
Mice, Inbred C57BL
Models, Molecular
Orthomyxoviridae Infections / immunology
Orthomyxoviridae Infections / prevention & control*
Orthomyxoviridae Infections / virology
Recombinant Fusion Proteins / chemistry
Recombinant Fusion Proteins / genetics
Recombinant Fusion Proteins / immunology
Vaccination / methods
Vaccines, Synthetic
Viral Matrix Proteins / genetics
Viral Matrix Proteins / immunology

Substances

Antibodies, Viral
Antigens, Viral
Hemagglutinin Glycoproteins, Influenza Virus
Immunoglobulin G
Influenza Vaccines
M1 protein, Influenza A virus
Recombinant Fusion Proteins
Vaccines, Synthetic
Viral Matrix Proteins

Abstract

Publication types

MeSH terms

Substances

Grants and funding