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

• Published in: Virology (New York, N.Y.) Vol. 566; pp. 143 - 152
• Main Authors: Park, Bo Ryoung, Subbiah, Jeeva, Kim, Ki-Hye, Kwon, Young-Man, Oh, Judy, Kim, Min-Chul, Shin, Chong-Hyun, Seong, Baik Lin, Kang, Sang-Moo
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.01.2022
• Subjects: 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; Live attenuated virus; M2e; 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; Recombinant influenza virus; Vaccination - methods; Vaccines, Synthetic; Viral Matrix Proteins - genetics; Viral Matrix Proteins - immunology; M2e; Recombinant influenza virus; Cross protection; Live attenuated virus
• ISSN: 0042-6822; 1096-0341
• DOI: 10.1016/j.virol.2021.12.003

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. •Recombinant 4xM2e-HA influenza viruses are effective in inducing M2e specific antibodies.•Hetero prime-boost vaccination induces more cross protective immunity.•M2e specific IgG and partially HA stalk IgG antibodies correlate with cross protection controlling lung viral replications.•Aged mice show lower capacity to induce IgG antibodies for immune-subdominant epitopes.