Key result
Immunization of macaques with an AS03-adjuvanted SARS-CoV-2 subunit vaccine generated extremely potent pan-sarbecovirus neutralizing antibodies, such as 25F9 and 20A7, which provided complete prophylactic protection against multiple sarbecoviruses in mice.
Why the study?
The rapid emergence of SARS-CoV-2 variants evading vaccine immunity created a global need for therapeutic countermeasures providing broad protection against SARS-CoV-2 and related sarbecoviruses.
Extremely potent pan-sarbecovirus neutralizing antibodies isolated from vaccinated macaques provide complete prophylactic protection against multiple SARS-CoV-2 variants and related sarbecoviruses in mice.
This is the authors' abstract. We don't add key points for this paper.
The rapid emergence of SARS-CoV-2 variants that evade immunity to vaccination has placed a global health imperative on the development of therapeutic countermeasures that provide broad protection against SARS-CoV-2 and related sarbecoviruses. Here, we identified extremely potent pan-sarbecovirus antibodies from non-human primates vaccinated with an AS03 adjuvanted subunit vaccine against SARS-CoV-2 that recognize conserved epitopes in the receptor binding domain (RBD) with femtomolar affinities. Longitudinal analysis revealed progressive accumulation of somatic mutation in the immunoglobulin genes of antigen-specific memory B cells for at least one year following primary vaccination. 514 monoclonal antibodies (mAbs) were generated from antigen-specific memory B cells. Antibodies isolated at 5 to 12 months following vaccination displayed greater potency and breadth, relative to those identified at 1.4 months. Notably, 15 out of 338 (∼4.4%) antibodies isolated at 1.4∼6 months after the primary vaccination showed extraordinary neutralization potency against SARS-CoV-2 omicron BA.1, despite the absence of BA.1 neutralization in serum. Two of them, 25F9 and 20A7, neutralized authentic clade Ia sarbecoviruses (SARS-CoV, WIV-1, SHC014) and clade Ib sarbecoviruses (SARS-CoV-2 D614G, SARS-CoV-2 BA.1, Pangolin-GD) with half-maximal inhibition concentrations of (0.85 ng/ml, 3 ng/ml, 6 ng/ml, 6 ng/ml, 42 ng/ml, 6 ng/ml) and (13 ng/ml, 2 ng/ml, 18 ng/ml, 9 ng/ml, 6 ng/ml, 345 ng/ml), respectively. Furthermore, 20A7 and 27A12 showed potent neutralization against all SARS-CoV-2 variants of concern and multiple Omicron sublineages, including BA.1, BA.2, BA.3, BA.4/5, BQ.1, BQ.1.1 and XBB variants. X-ray crystallography studies revealed the molecular basis of broad and potent neutralization through targeting conserved RBD sites. In vivo prophylactic protection of 25F9, 20A7 and 27A12 was confirmed in aged Balb/c mice. Notably, administration of 25F9 provided complete protection against SARS-CoV-2, SARS-CoV-2 BA.1, SARS-CoV, and SHC014 challenge, underscoring that these mAbs are promising pan-sarbecovirus therapeutic antibodies. One Sentence Summary: Extremely potent pan-sarbecovirus neutralizing antibodies.
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May guide broad sarbecovirus vaccine design; leaves open human translation from NHP data.
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Feng et al. (2023) studied SARS-CoV-2 infection (preclinical model) (n=11). AS03-adjuvanted monovalent subunit vaccine against SARS-CoV-2 and isolated monoclonal antibodies (e.g., 25F9, 20A7) vs. Isotype control antibody (in mice) was evaluated on Neutralization potency (IC50) and in vivo protection against SARS-CoV-2 variants and sarbecoviruses. Immunization of macaques with an AS03-adjuvanted SARS-CoV-2 subunit vaccine generated extremely potent pan-sarbecovirus neutralizing antibodies, such as 25F9 and 20A7, which provided complete prophylactic protection against multiple sarbecoviruses in mice.
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