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Generation of Escape Variants of Neutralizing Influenza Virus Monoclonal Antibodies
Published on: August 29, 2017
Passively transferred M2e-specific monoclonal antibody reduces influenza A virus transmission in mice
Annasaheb Kolpe1, Bert Schepens1, Liang Ye2
1VIB Center for Medical Biotechnology, VIB, Technologiepark 927, Ghent, B-9052, Belgium; Department of Biomedical Molecular Biology, Ghent University, Ghent, B-9052, Belgium.
Abstract:
Influenza represents a global public health threat. Currently available influenza vaccines are effective against strain-matched influenza A and B viruses but do not protect against novel pandemic viruses. Vaccine candidates that target conserved B or T cell epitopes of influenza viruses could circumvent this shortcoming. The conserved extracellular domain of matrix protein 2 (M2e) of influenza A is an example of such a broadly protective vaccine candidate. Protection by M2e-based vaccine candidates largely depends on M2e-specific IgG antibodies. Here we show that the M2e-specific IgG2a monoclonal antibody 65 (MAb 65) can reduce influenza A/Udorn/72 (H3N2) and A/Hong Kong/68 (H3N2) virus plaque formation. This effect was not observed with other influenza A virus strains tested. We further show that passive transfer of MAb 65 to mice can reduce viral loads in the upper and lower airways, which results in reduced transmission of A/Udorn/72 and A/Hong Kong/68 viruses to cohoused, unimmunized contact mice. Virus restriction by passively transferred Mab 65 was significantly less pronounced in Fcgr1-/-Fcgr3-/- mutant mice compared with wild type controls, suggesting that in vivo protection provided by MAb 65 depends on Fcγ receptor-mediated antibody effector mechanisms. We conclude that M2e-based antibody immune therapy has the potential to diminish influenza A virus replication in the immunized host as well as in exposed naïve contacts.
Insights
Monoclonal antibody 65 targeting the M2e protein of influenza A viruses can reduce viral replication and transmission. This antibody-based immunotherapy shows potential for controlling influenza A infections in both treated and exposed individuals.
Area of Science:
- Virology
- Immunology
- Vaccinology
Background:
- Influenza A poses a global health risk, with current vaccines lacking protection against novel strains.
- Vaccine candidates targeting conserved epitopes, like the M2e protein, offer broad protection.
- M2e-based vaccines rely on M2e-specific IgG antibodies for efficacy.
Purpose of the Study:
- To investigate the protective potential of M2e-specific IgG2a monoclonal antibody 65 (MAb 65) against influenza A.
- To determine if MAb 65 can reduce viral replication and transmission in vivo.
- To elucidate the Fcγ receptor-dependent mechanisms of MAb 65-mediated protection.
Main Methods:
- Assessed MAb 65's ability to reduce plaque formation of influenza A viruses.
- Evaluated the effect of passive MAb 65 transfer on viral loads and transmission in mice.
- Compared MAb 65 efficacy in wild-type versus Fcγ receptor-deficient mice.
Main Results:
- MAb 65 significantly reduced plaque formation for influenza A/Udorn/72 and A/Hong Kong/68 strains.
- Passive transfer of MAb 65 decreased viral loads in mouse airways and reduced virus transmission to contacts.
- Protection was diminished in Fcγ receptor-deficient mice, indicating Fcγ receptor-mediated mechanisms.
Conclusions:
- M2e-specific MAb 65 demonstrates efficacy in reducing influenza A virus replication and transmission.
- Fcγ receptor engagement is crucial for the in vivo protective effects of MAb 65.
- M2e-based antibody immune therapy presents a promising strategy for controlling influenza A.
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