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Neutralization of Mu and C.1.2 SARS-CoV-2 Variants by Vaccine-elicited Antibodies in Individuals With and Without Previous History of Infection

View ORCID ProfileTakuya Tada, Hao Zhou, View ORCID ProfileBelinda M. Dcosta, Marie I. Samanovic, Amber Cornelius, Ramin S. Herati, Mark J. Mulligan, View ORCID ProfileNathaniel R. Landau
doi: https://doi.org/10.1101/2021.10.19.463727
Takuya Tada
1Department of Microbiology, NYU Grossman School of Medicine, New York, NY, USA
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Hao Zhou
1Department of Microbiology, NYU Grossman School of Medicine, New York, NY, USA
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Belinda M. Dcosta
1Department of Microbiology, NYU Grossman School of Medicine, New York, NY, USA
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Marie I. Samanovic
2NYU Langone Vaccine Center and Department of Medicine, NYU Grossman School of Medicine, New York, NY, USA
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Amber Cornelius
2NYU Langone Vaccine Center and Department of Medicine, NYU Grossman School of Medicine, New York, NY, USA
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Ramin S. Herati
2NYU Langone Vaccine Center and Department of Medicine, NYU Grossman School of Medicine, New York, NY, USA
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Mark J. Mulligan
2NYU Langone Vaccine Center and Department of Medicine, NYU Grossman School of Medicine, New York, NY, USA
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Nathaniel R. Landau
1Department of Microbiology, NYU Grossman School of Medicine, New York, NY, USA
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  • ORCID record for Nathaniel R. Landau
  • For correspondence: nathaniel.landau@med.nyu.edu
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Abstract

Recently identified SARS-CoV-2 variants Mu and C.1.2 have mutations in the receptor binding domain and N- and C-terminal domains that might confer resistance to natural and vaccine-elicited antibody. Analysis with pseudotyped lentiviruses showed that viruses with the Mu and C.1.2 spike proteins were partially resistant to neutralization by antibodies in convalescent sera and those elicited by mRNA and adenoviral vector-based vaccine-elicited antibodies. Virus with the C.1.2 variant spike, which is heavily mutated, was more neutralization-resistant than that of any of variants of concern. The resistance of the C.1.2 spike was caused by a combination of the RBD mutations N501Y, Y449H and E484K and the NTD mutations. Although Mu and C.1.2 were partially resistant to neutralizing antibody, neutralizing titers elicited by mRNA vaccination remained above what is found in convalescent sera and thus are likely to remain protective against severe disease. The neutralizing titers of sera from infection-experienced BNT162b2-vaccinated individuals, those with a history of previous SARS-CoV-2 infection, were as much as 15-fold higher than those of vaccinated individuals without previous infection and effectively neutralized all of the variants. The findings demonstrate that individuals can raise a broadly neutralizing humoral response by generating a polyclonal response to multiple spike protein epitopes that should protect against current and future variants.

Competing Interest Statement

The authors declare no competing interests except M.J.M. who received research grants from Lilly, Pfizer, and Sanofi, and serves on advisory boards for Pfizer, Merck, and Meissa Vaccines.

Copyright 
The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. All rights reserved. No reuse allowed without permission.
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Posted October 20, 2021.
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Neutralization of Mu and C.1.2 SARS-CoV-2 Variants by Vaccine-elicited Antibodies in Individuals With and Without Previous History of Infection
Takuya Tada, Hao Zhou, Belinda M. Dcosta, Marie I. Samanovic, Amber Cornelius, Ramin S. Herati, Mark J. Mulligan, Nathaniel R. Landau
bioRxiv 2021.10.19.463727; doi: https://doi.org/10.1101/2021.10.19.463727
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Neutralization of Mu and C.1.2 SARS-CoV-2 Variants by Vaccine-elicited Antibodies in Individuals With and Without Previous History of Infection
Takuya Tada, Hao Zhou, Belinda M. Dcosta, Marie I. Samanovic, Amber Cornelius, Ramin S. Herati, Mark J. Mulligan, Nathaniel R. Landau
bioRxiv 2021.10.19.463727; doi: https://doi.org/10.1101/2021.10.19.463727

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