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Detection of Neutralization-sensitive Epitopes in Antigens Displayed on Virus-Like Particle VLP-Based Vaccines Using a Capture Assay
Published on: February 10, 2022
Potent neutralization by antibodies targeting the MPXV A28 protein
Ron Yefet1, Leandro Battini2, Mathieu Hubert3
1Department of Clinical Microbiology and Immunology, Gray Faculty of Medical and Health Sciences, Tel Aviv University, Tel Aviv, Israel.
Abstract:
Monkeypox virus (MPXV) is the most pathogenic Poxvirus in circulation, yet key viral antigens remain immunologically unexplored. We isolate and characterize a panel of monoclonal antibodies (mAbs) targeting MPXV A28 (OPG153), an important membranal protein present on mature MPXV virions. From male convalescent individuals, we isolate anti-A28 mAbs alongside additional mAbs targeting the A35 and H3 proteins. Anti-A28 mAbs potently neutralize MPXV and Vaccinia virus (VACV) through complement-dependent mechanisms involving C1q and C3 deposition. High-resolution crystal structures of two anti-A28 mAbs, 10M2146 and 8M2110, in complex with VACV A26 reveal two distinct and highly conserved proximal epitopes within the N-terminal domain. Passive transfer of 8M2110 modestly attenuates disease in infected female mice. Moreover, immunization with A28 elicits antigen-specific B cells and robust neutralizing antibody responses and provides protection against lethal VACV challenge. These findings identify MPXV A28 as a promising central target for the induction of neutralizing antibodies and antiviral interventions.
Insights
Researchers developed monoclonal antibodies targeting Monkeypox virus (MPXV) A28 protein. These antibodies neutralize MPXV and Vaccinia virus (VACV), offering a potential new antiviral intervention strategy.
Area of Science:
- Virology
- Immunology
- Structural Biology
Background:
- Monkeypox virus (MPXV) is a highly pathogenic Poxvirus with unexplored antigens.
- MPXV A28 is a key viral membrane protein on mature virions.
Purpose of the Study:
- To isolate and characterize monoclonal antibodies (mAbs) targeting MPXV A28.
- To investigate the neutralizing capabilities and mechanisms of anti-A28 mAbs.
- To explore A28 as a target for antiviral interventions.
Main Methods:
- Isolation and characterization of anti-A28 mAbs from convalescent individuals.
- Assessment of viral neutralization assays, including complement-dependent mechanisms (C1q, C3 deposition).
- High-resolution crystal structures of anti-A28 mAbs complexed with VACV A26.
- In vivo studies involving passive antibody transfer and A28 immunization in mouse models.
Main Results:
- Isolated potent anti-A28 mAbs that neutralize MPXV and Vaccinia virus (VACV).
- Demonstrated complement-dependent neutralization mechanisms involving C1q and C3.
- Determined high-resolution structures revealing conserved epitopes on A28.
- Showed modest disease attenuation via passive transfer and protection against VACV challenge upon immunization.
Conclusions:
- MPXV A28 is a viable target for inducing neutralizing antibodies.
- Anti-A28 mAbs represent a promising strategy for antiviral interventions against poxviruses.
- Further research into A28-based therapies is warranted for poxvirus control.
