Impact of hemagglutination activity and M2e immunity on conferring protection against influenza viruses

• Published in: Virology (New York, N.Y.) Vol. 574; pp. 37 - 46
• Main Authors: Oh, Judy, Subbiah, Jeeva, Kim, Ki-Hye, Park, Bo Ryoung, Bhatnagar, Noopur, Garcia, Karla Ruiz, Liu, Rong, Jung, Yu-Jin, Shin, Chong-Hyun, Seong, Baik-Lin, Kang, Sang-Moo
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.09.2022
• Subjects: Animals; Antibodies, Viral; Cross Protection; Hemagglutination; Hemagglutinin integrity; Humans; Influenza Vaccines; Influenza, Human - prevention & control; M2e immunity; Mice; Mice, Inbred BALB C; Orthomyxoviridae; Orthomyxoviridae Infections; Protection; M2e immunity; Hemagglutinin integrity; Protection
• ISSN: 0042-6822; 1096-0341
• DOI: 10.1016/j.virol.2022.07.010

To improve cross-protection of influenza vaccination, we tested conjugation of conserved M2e epitopes to the surface of inactivated influenza virus (iPR8-M2e*). Treatment of virus with chemical cross-linker led to diminished hemagglutination activity and failure to induce hemagglutination inhibiting antibodies. Conjugated iPR8-M2e* vaccine was less protective against homologous and heterosubtypic viruses, despite the induction of virus-specific binding IgG antibodies. In alternative approaches to enhance cross-protection, we developed a genetically linked chimeric protein (M2e-B stalk) vaccine with M2e of influenza A and hemagglutinin (HA) stalk of influenza B virus. Vaccination of mice with inactivated influenza A virus supplemented with M2e-B stalk effectively induced hemagglutination inhibiting antibodies, humoral and cellular M2e immune responses, and enhanced heterosubtypic protection. This study demonstrates the importance of HA functional integrity in influenza vaccine efficacy and that supplementation of influenza vaccines with M2e-B stalk protein could be a feasible strategy of improving cross-protection against influenza viruses. •Chemical modification of inactivated influenza virus can lead to a loss of hemagglutination activity.•HA functional integrity in influenza vaccines is critical for inducing protective antibodies and homo and hetero protection.•Supplementing M2e immunity to influenza vaccination provides a feasible strategy for enhancing cross protection.