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- Title
SARS-CoV-2 BA.1 variant is neutralized by vaccine booster–elicited serum but evades most convalescent serum and therapeutic antibodies.
- Authors
Lusvarghi, Sabrina; Pollett, Simon D.; Neerukonda, Sabari Nath; Wang, Wei; Wang, Richard; Vassell, Russell; Epsi, Nusrat J.; Fries, Anthony C.; Agan, Brian K.; Lindholm, David A.; Colombo, Christopher J.; Mody, Rupal; Ewers, Evan C.; Lalani, Tahaniyat; Ganesan, Anuradha; Goguet, Emilie; Hollis-Perry, Monique; Coggins, Si'Ana A.; Simons, Mark P.; Katzelnick, Leah C.
- Abstract
The rapid spread of the highly contagious Omicron variant of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) along with its high number of mutations in the spike gene has raised alarms about the effectiveness of current medical countermeasures. To address this concern, we measured the neutralization of the Omicron BA.1 variant pseudovirus by postvaccination serum samples after two and three immunizations with the Pfizer/BioNTech162b2 SARS-CoV-2 mRNA (Pfizer/BNT162b2) vaccine, convalescent serum samples from unvaccinated individuals infected by different variants, and clinical-stage therapeutic antibodies. We found that titers against the Omicron variant were low or undetectable after two immunizations and in many convalescent serum samples, regardless of the infecting variant. A booster vaccination increased titers more than 30-fold against Omicron to values comparable to those seen against the D614G variant after two immunizations. Neither age nor sex was associated with the differences in postvaccination antibody responses. We also evaluated 18 clinical-stage therapeutic antibody products and an antibody mimetic protein product obtained directly from the manufacturers. Five monoclonal antibodies, the antibody mimetic protein, three antibody cocktails, and two polyclonal antibody preparations retained measurable neutralization activity against Omicron with a varying degree of potency. Of these, only three retained potencies comparable to the D614G variant. Two therapeutic antibody cocktails in the tested panel that are authorized for emergency use in the United States did not neutralize Omicron. These findings underscore the potential benefit of mRNA vaccine boosters for protection against Omicron and the need for rapid development of antibody therapeutics that maintain potency against emerging variants. Variable variant neutralization: As the SARS-CoV-2 Omicron BA.1 variant spreads across the world, the degree to which vaccine- and infection-elicited antibodies conferred protection from infection and severe disease remained unclear. Moreover, the neutralizing capacity of therapeutic antibodies was not well defined. Here, Lusvarghi and colleagues tested the ability of serum from individuals previously infected with SARS-CoV-2, serum from individuals vaccinated and boosted with mRNA vaccines, and therapeutic antibodies to neutralize the Omicron BA.1 variant. The authors found that those receiving three doses of a SARS-CoV-2 mRNA vaccine had Omicron BA.1–neutralizing antibodies. However, convalescent serum poorly neutralized Omicron BA.1, regardless of infecting variant. Last, most, but not all, therapeutic antibodies tested lost potency against the Omicron BA.1 variant. Together, these results underscore the value of vaccination and highlight the need to develop therapeutics that can neutralize Omicron and other emerging SARS-CoV-2 variants.
- Subjects
PFIZER Inc.; SARS-CoV-2; CONVALESCENT plasma; IMMUNOGLOBULINS; VIRAL antibodies; SARS-CoV-2 Omicron variant; MONOCLONAL antibodies
- Publication
Science Translational Medicine, 2022, Vol 14, Issue 645, p1
- ISSN
1946-6234
- Publication type
Article
- DOI
10.1126/scitranslmed.abn8543