M2e‐specific antibodies protect against influenza PR8 virus in an isotype and route dependent manner

Abstract

The ectodomain of influenza matrix protein 2 (M2e) is a promising target for the development of universal prophylactic and therapeutic agents against influenza viruses of different subtypes. We constructed three M2e-specific monoclonal antibody variants, M2A1-1 (IgG1), M2A1-2a (IgG2a), M2A1-2b (IgG2b), which have the same Fab region targeting the M2e epitope but different isotypes, and compared their protective efficacy in influenza PR8-infected mice. We found that anti-M2e antibodies provided protection against influenza virus in a subtype-dependent manner, with the IgG2a variant providing significantly better protection with lower virus titers and milder lung injury than IgG1 and IgG2b isotypes. Additionally, we observed that the protective efficacy was dependent on the administration routes, with intranasal administration of antibody providing better protection than intraperitoneal administration. The timing of administration was also critical in determining the protective efficacy; while all the antibody isotypes provided protection when administered before influenza challenge, only IgG2a provided minimal protection when the antibodies were administered after virus challenge. These results provide valuable information for optimizing the therapeutics usage of M2e-based antibodies and furthering the development of M2e-based universal influenza vaccines.

Respiratory delivery of passive immunotherapies for SARS-CoV-2 prophylaxis and therapy

“… 6 In comparison to parenteral treatment, inhalation of IgG’s gave better protection and a greater therapeutic response in pneumonia models using the influenza virus. 7 , 8 Nasal delivery of viral vectors encoding anti-influenza IgG has also been tested successfully in mice. 9 More limited experiences have been reported for monkeypox virus 10 and respiratory syncytial virus.…”