Broadly Neutralizing Antibodies Against Sarbecoviruses Generated by Immunization of Macaques with an As03-Adjuvanted Covid-19 Vaccine

Strategic Insights -

Research conducted at Stanford University has identified extremely potent monoclonal antibodies (mAbs) that neutralized multiple sarbecoviruses from macaques vaccinated with AS03-adjuvanted monovalent subunit vaccines. These findings have significant implications for the development of countermeasures against SARS-CoV-2 and related sarbecoviruses. The research was supported by various institutions, including the Bill & Melinda Gates Foundation, the NIH National Institute of Allergy & Infectious Diseases, and the US Food & Drug Administration.

Key Takeaways:

  • The rapid emergence of SARS-CoV-2 variants that evade immunity elicited by vaccination has necessitated the development of countermeasures that provide broad protection against SARS-CoV-2 and related sarbecoviruses.
  • The study identified extremely potent monoclonal antibodies (mAbs) that neutralized multiple sarbecoviruses from macaques vaccinated with AS03-adjuvanted monovalent subunit vaccines.
  • The mAbs, 25F9, 20A7, and 27A12, demonstrated potent neutralization against all SARS-CoV-2 variants, including BA.1, BA.2, BA.3, BA.4/5, BQ.1, BQ.1.1, and XBB.
  • Crystallography studies revealed the molecular basis of broad and potent neutralization through targeting conserved sites within the RBD.
  • Prophylactic protection of 25F9, 20A7, and 27A12 was confirmed in mice, and administration of 25F9 particularly provided complete protection against SARS-CoV-2, BA.1, SARS-CoV, and SHC014 challenge.
  • The study concluded that the mAbs identified offer extremely potent and broad activity against sarbecoviruses.

Statistics:

  • 25F9, 20A7, and 27A12 mAbs neutralized all SARS-CoV-2 variants, including BA.1, BA.2, BA.3, BA.4/5, BQ.1, BQ.1.1, and XBB.
  • 15 out of 338 (4.4%) antibodies isolated at 1.4 to 6 months after primary vaccination showed potency against SARS-CoV-2 BA.1, despite the absence of serum BA.1 neutralization.
  • Crystallography studies revealed the molecular basis of broad and potent neutralization through targeting conserved sites within the RBD.

Sources:

  • NewsRx. Data on COVID-19 Reported by Researchers at Stanford University (Broadly Neutralizing Antibodies Against Sarbecoviruses Generated By Immunization of Macaques With an As03-adjuvanted Covid-19 Vaccine). Medical Letter on the CDC & FDA. July 9, 2023; p 148.
  • Bali Pulendran, Stanford University, Inst Immun Transplantat & Infect, Stanford, CA 94305, United States.
  • Yupeng Feng, Mengyun Hu, Prabhu S. Arunachalam, Meng Yuan, Xueyong Zhu, Ian A. Wilson, John M. Powers, Jennifer E. Munt, Sarah R. Leist, Lily E. Adams, Michael L. Mallory, Trevor D. Scobey, Ralph S. Baric, Lorenza Bellusci, JungHyun Kim, Surender Khurana, Kaitlin R. Sprouse, David Veesler, Neil P. King, Sumana Sundaramurthy, Lisa M. Shirreff, Francois J. Villinger, Alberto Moreno, Derek T. O'Hagan, Harry Kleanthous, and Mehul S. Suthar.