TY - JOUR
T1 - SARS-CoV-2 BA.1 variant is neutralized by vaccine booster-elicited serum but evades most convalescent serum and therapeutic antibodies
AU - Lusvarghi, Sabrina
AU - Pollett, Simon D.
AU - Neerukonda, Sabari Nath
AU - Wang, Wei
AU - Wang, Richard
AU - Vassell, Russell
AU - Epsi, Nusrat J.
AU - Fries, Anthony C.
AU - Agan, Brian K.
AU - Lindholm, David A.
AU - Colombo, Christopher J.
AU - Mody, Rupal
AU - Ewers, Evan C.
AU - Lalani, Tahaniyat
AU - Ganesan, Anuradha
AU - Goguet, Emilie
AU - Hollis-Perry, Monique
AU - Coggins, Si'Ana A.
AU - Simons, Mark P.
AU - Katzelnick, Leah C.
AU - Wang, Gregory
AU - Tribble, David R.
AU - Bentley, Lisa
AU - Eakin, Ann E.
AU - Broder, Christopher C.
AU - Erlandson, Karl J.
AU - Laing, Eric D.
AU - Burgess, Timothy H.
AU - Mitre, Edward
AU - Weiss, Carol D.
N1 - Publisher Copyright:
Copyright © 2022 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science.
PY - 2022/5/18
Y1 - 2022/5/18
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=85130278825&partnerID=8YFLogxK
U2 - 10.1126/scitranslmed.abn8543
DO - 10.1126/scitranslmed.abn8543
M3 - Article
C2 - 35380448
AN - SCOPUS:85130278825
SN - 1946-6234
VL - 14
JO - Science Translational Medicine
JF - Science Translational Medicine
IS - 645
M1 - eabn8543
ER -