Universal antibody targeting the highly conserved fusion peptide provides cross-protection in mice. Issue 5 (30th November 2022)

• Record Type: Journal Article
• Authors: Muralidharan, Abenaya; Gravel, Caroline; Harris, Greg; Hashem, Anwar M.; Zhang, Wanyue; Safronetz, David; Van Domselaar, Gary; Krammer, Florian; Sauve, Simon; Rosu-Myles, Michael; Wang, Lisheng; Chen, Wangxue; Li, Xuguang
• Is Part Of: Human vaccines & immunotherapeutics. Volume 18:Issue 5(2022)
• Publication Date: 2022-11-30
• Subjects: Influenza -- universal antibody -- Uni-1 -- antibody-dependent cellular cytotoxicity (ADCC) -- cross-protection; Vaccines -- Periodicals; 615.372
• DOI: 10.1080/21645515.2022.2083428
• Languages: English
• ISSNs: 2164-5515

Abstract

ABSTRACT: Influenza is a major public health concern causing millions of hospitalizations every year. The current vaccines need annual updating based on prediction of likely strains in the upcoming season. However, mismatches between vaccines and the actual circulating viruses can occur, reducing vaccine effectiveness significantly because of the remarkably high rate of mutation in the viral glycoprotein, hemagglutinin (HA). Clearly, it would be of great interest to determine the potential role of universally conserved epitopes in inducing protective immunity. Here, an antibody against the 14-aa fusion peptide sequence at the N -terminus of the HA2 subunit (Uni-1) was investigated for its ability to elicit antibody-dependent cellular cytotoxicity (ADCC) in vitro and cross-protection against lethal infection in animals. Uni-1, known to neutralize influenza type A (IAV) in vitro, was found to induce strong ADCC against diverse influenza viruses, including human and avian IAVs and both lineages of type B (IBV). The ADCC effects against human IAVs by Uni-1 was comparable to ADCC induced by well-characterized antibodies, F10 and FI6V3. Importantly, mice treated with Uni-1 were protected against lethal challenge of IAV and IBV. These results revealed the versatile effector functions of this universal antibody against markedly diverse strains of both IAV and IBV. Highlights: The fusion peptide is the only universally conserved epitope in both IAV and IBV Mono-specific universal antibody induces strong ADCC against human and avian IAV Mono-specific universal antibody induces strong ADCC against IBV from both genetic lineages of IBV The antibody has bi-functional effector functions against several influenza viruses