Multiple heterologous M2 extracellular domains presented on virus-like particles confer broader and stronger M2 immunity than live influenza A virus infection

• Type of Material: Article
• Authors: Min-Chul Kim, Georgia State University; Jong-Seok Lee, Georgia State University; Young-Man Kwon, Georgia State University; O Eunju, Georgia State University; Youn-Jeong Lee, Animal, Plant and Fisheries Quarantine and Inspection Agency; Jun-Gu Choi, Animal, Plant and Fisheries Quarantine and Inspection Agency; Baozhong Wang, Emory University; Richard W Compans, Emory University; Sang-Moo Kang, Georgia State University
• Language: English
• Date: 2013-09-01
• Publisher: Elsevier Masson
• Publication Version: Author Accepted Manuscript (After Peer Review)
• Copyright Statement: © 2013 Elsevier B.V. All rights reserved.
• License: Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International
• Final Published Version (URL): http://dx.doi.org/10.1016/j.antiviral.2013.06.010
• Title of Journal or Parent Work: Antiviral Research
• ISSN: 0166-3542
• Volume: 99
• Issue: 3
• Start Page: 328
• End Page: 335
• Grant/Funding Information: This work was supported by NIH/NIAID grants AI0680003 (R.W.C.), AI105170 (S.M.K.) AI093772 (S.M.K.), and AI087782 (S.M.K.); Georgia State University & Georgia Research Alliance research funds (S.M.K); TOBICO Co. & Dankook University (S.M.K); and Animal, Plant, and Fisheries Quarantine Inspection Agency grant (I-1541781-2012-15-01), Republic of Korea.
• Keywords: VACCINATION; CONJUGATE VACCINES; M2e cross-reactivity; MUCOSAL; IMMUNOGENICITY; IMPROVED CROSS-PROTECTION; ECTODOMAIN; Cross protection; M2e VLPs; PROVIDES; Pharmacology & Pharmacy; SUBTYPES; Virology; INDUCTION; Science & Technology; MATRIX PROTEIN-2; Life Sciences & Biomedicine
• Research Categories: Health Sciences, Immunology; Biology, Virology

Abstract

The influenza M2 ectodomain (M2e) is poorly immunogenic and has some amino acid changes among isolates from different host species. We expressed a tandem repeat construct of heterologous M2e sequences (M2e5x) derived from human, swine, and avian origin influenza A viruses on virus-like particles (M2e5x VLPs) in a membrane-anchored form. Immunization of mice with M2e5x VLPs induced protective antibodies cross-reactive to antigenically different influenza A viruses and conferred cross protection. Anti-M2e antibodies induced by heterologous M2e5x VLPs showed a wider range of cross reactivity to influenza A viruses at higher levels than those by live virus infection, homologous M2e VLPs, or M2e monoclonal antibody 14C2. Fc receptors were found to be important for mediating protection by immune sera from M2e5x VLP vaccination. The present study provides evidence that heterologous recombinant M2e5x VLPs can be more effective in inducing protective M2e immunity than natural virus infection and further supports an approach for developing an effective universal influenza vaccine.