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<p>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.</p>

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Potent neutralization by antibodies targeting the MPXV A28 protein

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2025年12月10日

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  • Ron Yefet,
  • Leandro Battini,
  • Mathieu Hubert,
  • Katya Rakayev,
  • Florence Guivel-Benhassine,
  • Noam Rattner,
  • Francoise Porrot,
  • Lilach Abramovitz,
  • Gilad Ostashinsky,
  • Noam Ben-Shalom,
  • Jeanne Postal,
  • Ksenia Polonsky,
  • Maya Ralph-Altman,
  • Sireen Sweed,
  • Tal Korner,
  • Nadav Friedel,
  • David Hagin,
  • Eli Sprecher,
  • Zvi Fishelson,
  • Oren Kobiler,
  • Lihi Adler-Abramovich,
  • Olivier Schwartz,
  • Pablo Guardado-Calvo,
  • Natalia T. Freund

摘要

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.