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Updated: Jul 30, 2025
An Optimized Hemagglutination Inhibition HI Assay to Quantify Influenza-specific Antibody Titers
Published on: December 1, 2017
M2e-specific antibodies protect against influenza PR8 virus in an isotype and route dependent manner
Tingting Sun1,2, Yingdan Wang1, Peng Zou1
1Shanghai Public Health Clinical Center and Shanghai Institute of Infectious Disease and Biosecurity, Key Laboratory of Medical Molecular Virology (MOE/NHC/CAMS), School of Basic Medical Sciences, Fudan University, Shanghai, China.
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.
Insights
Influenza M2e antibodies show promise for universal vaccines. The IgG2a variant offered superior protection against influenza in mice, with intranasal delivery and pre-challenge timing being most effective.
Area of Science:
- Immunology
- Virology
- Vaccinology
Background:
- The ectodomain of influenza matrix protein 2 (M2e) is a key target for universal influenza virus vaccines.
- Developing broadly protective influenza therapeutics remains a critical public health goal.
Purpose of the Study:
- To compare the protective efficacy of different M2e-specific monoclonal antibody isotypes (IgG1, IgG2a, IgG2b) against influenza.
- To evaluate the impact of administration route and timing on antibody-mediated protection.
Main Methods:
- Construction of three M2e-specific monoclonal antibody variants with identical Fab regions but differing isotypes (IgG1, IgG2a, IgG2b).
- Assessment of antibody efficacy in a mouse model of influenza PR8 infection.
- Analysis of virus titers, lung injury, administration routes, and timing of antibody administration.
Main Results:
- The IgG2a M2e-specific antibody variant demonstrated significantly better protection compared to IgG1 and IgG2b isotypes.
- Intranasal administration of antibodies was more effective than intraperitoneal administration.
- Pre-challenge antibody administration was crucial for protection; post-challenge administration showed minimal efficacy, even with IgG2a.
Conclusions:
- M2e-specific antibodies, particularly the IgG2a isotype, offer significant protection against influenza virus infection.
- Optimizing administration route (intranasal) and timing (pre-challenge) is essential for maximizing the therapeutic potential of M2e antibodies.
- These findings support the development of M2e-based universal influenza vaccines and therapeutics.
