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Circulating SARS-CoV-2 variants escape neutralization by vaccine-induced humoral immunity.
medRxiv. 2021 Feb 18M

Abstract

Vaccination elicits immune responses capable of potently neutralizing SARS-CoV-2. However, ongoing surveillance has revealed the emergence of variants harboring mutations in spike, the main target of neutralizing antibodies. To understand the impact of globally circulating variants, we evaluated the neutralization potency of 48 sera from BNT162b2 and mRNA-1273 vaccine recipients against pseudoviruses bearing spike proteins derived from 10 strains of SARS-CoV-2. While multiple strains exhibited vaccine-induced cross-neutralization comparable to wild-type pseudovirus, 5 strains harboring receptor-binding domain mutations, including K417N/T, E484K, and N501Y, were highly resistant to neutralization. Cross-neutralization of B.1.351 variants was weak and comparable to SARS-CoV and bat-derived WIV1-CoV, suggesting that a relatively small number of mutations can mediate potent escape from vaccine responses. While the clinical impact of neutralization resistance remains uncertain, these results highlight the potential for variants to escape from neutralizing humoral immunity and emphasize the need to develop broadly protective interventions against the evolving pandemic.

Authors+Show Affiliations

These authors contributed equally. Department of Pathology, Massachusetts General Hospital, Boston, MA, 02114, USA. Department of Pathology, Brigham and Women's Hospital, Boston, MA, 02115, USA.These authors contributed equally. Ragon Institute of MGH, MIT, and Harvard, Cambridge, MA, 02139, USA.These authors contributed equally. Ragon Institute of MGH, MIT, and Harvard, Cambridge, MA, 02139, USA.Ragon Institute of MGH, MIT, and Harvard, Cambridge, MA, 02139, USA.Ragon Institute of MGH, MIT, and Harvard, Cambridge, MA, 02139, USA.Ragon Institute of MGH, MIT, and Harvard, Cambridge, MA, 02139, USA.Ragon Institute of MGH, MIT, and Harvard, Cambridge, MA, 02139, USA.Vaccine and Immunotherapy Center, Massachusetts General Hospital, Boston, MA, 02129, USA.Vaccine and Immunotherapy Center, Massachusetts General Hospital, Boston, MA, 02129, USA. Pedriatric Infectious Disease, Massachusetts General Hospital for Children, Boston, MA 02114, USA.Vaccine and Immunotherapy Center, Massachusetts General Hospital, Boston, MA, 02129, USA. Department of Medicine, Massachusetts General Hospital, Boston, MA, 02114, USA.Africa Health Research Institute, Durban, 4001, South Africa. School of Laboratory Medicine and Medical Sciences, University of KwaZulu-Natal, Durban, 4041 South Africa. Max Planck Institute for Infection Biology, Berlin, 10117, Germany.Ragon Institute of MGH, MIT, and Harvard, Cambridge, MA, 02139, USA.Department of Pathology, Massachusetts General Hospital, Boston, MA, 02114, USA.Department of Medicine, Massachusetts General Hospital, Boston, MA, 02114, USA. Dana-Farber Cancer Institute, Boston, MA, 02215, USA. Center for the AIDS Programme of Research in South Africa, Durban, 4001, South Africa.Ragon Institute of MGH, MIT, and Harvard, Cambridge, MA, 02139, USA.

Pub Type(s)

Preprint

Language

eng

PubMed ID

33619506

Citation

Garcia-Beltran, Wilfredo F., et al. "Circulating SARS-CoV-2 Variants Escape Neutralization By Vaccine-induced Humoral Immunity." MedRxiv : the Preprint Server for Health Sciences, 2021.
Garcia-Beltran WF, Lam EC, St Denis K, et al. Circulating SARS-CoV-2 variants escape neutralization by vaccine-induced humoral immunity. medRxiv. 2021.
Garcia-Beltran, W. F., Lam, E. C., St Denis, K., Nitido, A. D., Garcia, Z. H., Hauser, B. M., Feldman, J., Pavlovic, M. N., Gregory, D. J., Poznansky, M. C., Sigal, A., Schmidt, A. G., Iafrate, A. J., Naranbhai, V., & Balazs, A. B. (2021). Circulating SARS-CoV-2 variants escape neutralization by vaccine-induced humoral immunity. MedRxiv : the Preprint Server for Health Sciences. https://doi.org/10.1101/2021.02.14.21251704
Garcia-Beltran WF, et al. Circulating SARS-CoV-2 Variants Escape Neutralization By Vaccine-induced Humoral Immunity. medRxiv. 2021 Feb 18; PubMed PMID: 33619506.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Circulating SARS-CoV-2 variants escape neutralization by vaccine-induced humoral immunity. AU - Garcia-Beltran,Wilfredo F, AU - Lam,Evan C, AU - St Denis,Kerri, AU - Nitido,Adam D, AU - Garcia,Zeidy H, AU - Hauser,Blake M, AU - Feldman,Jared, AU - Pavlovic,Maia N, AU - Gregory,David J, AU - Poznansky,Mark C, AU - Sigal,Alex, AU - Schmidt,Aaron G, AU - Iafrate,A John, AU - Naranbhai,Vivek, AU - Balazs,Alejandro B, Y1 - 2021/02/18/ PY - 2021/2/23/entrez PY - 2021/2/24/pubmed PY - 2021/2/24/medline JF - medRxiv : the preprint server for health sciences JO - medRxiv N2 - Vaccination elicits immune responses capable of potently neutralizing SARS-CoV-2. However, ongoing surveillance has revealed the emergence of variants harboring mutations in spike, the main target of neutralizing antibodies. To understand the impact of globally circulating variants, we evaluated the neutralization potency of 48 sera from BNT162b2 and mRNA-1273 vaccine recipients against pseudoviruses bearing spike proteins derived from 10 strains of SARS-CoV-2. While multiple strains exhibited vaccine-induced cross-neutralization comparable to wild-type pseudovirus, 5 strains harboring receptor-binding domain mutations, including K417N/T, E484K, and N501Y, were highly resistant to neutralization. Cross-neutralization of B.1.351 variants was weak and comparable to SARS-CoV and bat-derived WIV1-CoV, suggesting that a relatively small number of mutations can mediate potent escape from vaccine responses. While the clinical impact of neutralization resistance remains uncertain, these results highlight the potential for variants to escape from neutralizing humoral immunity and emphasize the need to develop broadly protective interventions against the evolving pandemic. UR - https://www.unboundmedicine.com/medline/citation/33619506/Circulating_SARS_CoV_2_variants_escape_neutralization_by_vaccine_induced_humoral_immunity_ L2 - https://doi.org/10.1101/2021.02.14.21251704 DB - PRIME DP - Unbound Medicine ER -
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