Antigenic cartography of well-characterized human sera shows SARS-CoV-2 neutralization differences based on infection and vaccination history

Wei Wang; Sabrina Lusvarghi; Rahul Subramanian; Nusrat J Epsi; Richard Wang; Emilie Goguet; Anthony C Fries; Fernando Echegaray; Russell Vassell; Si'Ana A Coggins; Stephanie A Richard; David A Lindholm; Katrin Mende; Evan C Ewers; Derek T Larson; Rhonda E Colombo; Christopher J Colombo; Janet O Joseph; Julia S Rozman; Alfred Smith; Tahaniyat Lalani; Catherine M Berjohn; Ryan C Maves; Milissa U Jones; Rupal Mody; Nikhil Huprikar; Jeffrey Livezey; David Saunders; Monique Hollis-Perry; Gregory Wang; Anuradha Ganesan; Mark P Simons; Christopher C Broder; David R Tribble; Eric D Laing; Brian K Agan; Timothy H Burgess; Edward Mitre; Simon D Pollett; Leah C Katzelnick; Carol D Weiss

doi:10.1016/j.chom.2022.10.012

Antigenic cartography of well-characterized human sera shows SARS-CoV-2 neutralization differences based on infection and vaccination history

Cell Host Microbe. 2022 Dec 14;30(12):1745-1758.e7. doi: 10.1016/j.chom.2022.10.012. Epub 2022 Oct 21.

Authors

Wei Wang¹, Sabrina Lusvarghi¹, Rahul Subramanian², Nusrat J Epsi³, Richard Wang¹, Emilie Goguet⁴, Anthony C Fries⁵, Fernando Echegaray⁶, Russell Vassell¹, Si'Ana A Coggins⁴, Stephanie A Richard³, David A Lindholm⁷, Katrin Mende³, Evan C Ewers⁸, Derek T Larson⁸, Rhonda E Colombo⁹, Christopher J Colombo¹⁰, Janet O Joseph⁶, Julia S Rozman³, Alfred Smith¹¹, Tahaniyat Lalani¹², Catherine M Berjohn¹³, Ryan C Maves¹⁴, Milissa U Jones¹⁵, Rupal Mody¹⁶, Nikhil Huprikar¹⁷, Jeffrey Livezey¹⁸, David Saunders¹⁹, Monique Hollis-Perry²⁰, Gregory Wang²¹, Anuradha Ganesan²², Mark P Simons²³, Christopher C Broder²⁴, David R Tribble²³, Eric D Laing²⁴, Brian K Agan³, Timothy H Burgess²³, Edward Mitre²⁴, Simon D Pollett²⁵, Leah C Katzelnick²⁶, Carol D Weiss²⁷

Affiliations

¹ Center for Biologics Evaluation and Research, U.S. Food and Drug Administration, Silver Spring, MD, USA.
² Office of Data Science and Emerging Technologies, Office of Science Management and Operations, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA.
³ Infectious Diseases Clinical Research Program, Department of Preventive Medicine and Biostatistics, Uniformed Services University of the Health Sciences, Bethesda, MD, USA; Henry M. Jackson Foundation for the Advancement of Military Medicine, Inc., Bethesda, MD, USA.
⁴ Henry M. Jackson Foundation for the Advancement of Military Medicine, Inc., Bethesda, MD, USA; Department of Microbiology and Immunology, Uniformed Services University of the Health Sciences, Bethesda, MD, USA.
⁵ U.S. Air Force School of Aerospace Medicine, Wright-Patterson Air Force Base, Fairborn, OH, USA.
⁶ Viral Epidemiology and Immunity Unit, Laboratory of Infectious Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA.
⁷ Brooke Army Medical Center, Joint Base San Antonio-Fort Sam Houston, San Antonio, TX, USA; Department of Medicine, Uniformed Services University of the Health Sciences, Bethesda, MD, USA.
⁸ Fort Belvoir Community Hospital, Fort Belvoir, VA, USA.
⁹ Infectious Diseases Clinical Research Program, Department of Preventive Medicine and Biostatistics, Uniformed Services University of the Health Sciences, Bethesda, MD, USA; Henry M. Jackson Foundation for the Advancement of Military Medicine, Inc., Bethesda, MD, USA; Department of Medicine, Uniformed Services University of the Health Sciences, Bethesda, MD, USA; Madigan Army Medical Center, Tacoma, WA, USA.
¹⁰ Department of Medicine, Uniformed Services University of the Health Sciences, Bethesda, MD, USA; Madigan Army Medical Center, Tacoma, WA, USA.
¹¹ Naval Medical Center Portsmouth, Portsmouth, VA, USA.
¹² Infectious Diseases Clinical Research Program, Department of Preventive Medicine and Biostatistics, Uniformed Services University of the Health Sciences, Bethesda, MD, USA; Henry M. Jackson Foundation for the Advancement of Military Medicine, Inc., Bethesda, MD, USA; Naval Medical Center Portsmouth, Portsmouth, VA, USA.
¹³ Infectious Diseases Clinical Research Program, Department of Preventive Medicine and Biostatistics, Uniformed Services University of the Health Sciences, Bethesda, MD, USA; Department of Medicine, Uniformed Services University of the Health Sciences, Bethesda, MD, USA; Naval Medical Center San Diego, San Diego, CA, USA.
¹⁴ Infectious Diseases Clinical Research Program, Department of Preventive Medicine and Biostatistics, Uniformed Services University of the Health Sciences, Bethesda, MD, USA; Department of Medicine, Uniformed Services University of the Health Sciences, Bethesda, MD, USA; Section of Infectious Diseases, Wake Forest University School of Medicine, Winston-Salem, NC, USA.
¹⁵ Tripler Army Medical Center, Honolulu, HI, USA.
¹⁶ William Beaumont Army Medical Center, El Paso, TX, USA.
¹⁷ Walter Reed National Military Medical Center, Bethesda, MD, USA.
¹⁸ Department of Pediatrics, Uniformed Services University of the Health Sciences, Bethesda, MD, USA.
¹⁹ Department of Medicine, Uniformed Services University of the Health Sciences, Bethesda, MD, USA.
²⁰ Clinical Trials Center, Infectious Diseases Directorate, Naval Medical Research Center, Silver Spring, MD, USA.
²¹ General Dynamics Information Technology, Falls Church, VA, USA.
²² Infectious Diseases Clinical Research Program, Department of Preventive Medicine and Biostatistics, Uniformed Services University of the Health Sciences, Bethesda, MD, USA; Henry M. Jackson Foundation for the Advancement of Military Medicine, Inc., Bethesda, MD, USA; Walter Reed National Military Medical Center, Bethesda, MD, USA.
²³ Infectious Diseases Clinical Research Program, Department of Preventive Medicine and Biostatistics, Uniformed Services University of the Health Sciences, Bethesda, MD, USA.
²⁴ Department of Microbiology and Immunology, Uniformed Services University of the Health Sciences, Bethesda, MD, USA.
²⁵ Infectious Diseases Clinical Research Program, Department of Preventive Medicine and Biostatistics, Uniformed Services University of the Health Sciences, Bethesda, MD, USA; Henry M. Jackson Foundation for the Advancement of Military Medicine, Inc., Bethesda, MD, USA. Electronic address: spollett@idcrp.org.
²⁶ Viral Epidemiology and Immunity Unit, Laboratory of Infectious Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA. Electronic address: leah.katzelnick@nih.gov.
²⁷ Center for Biologics Evaluation and Research, U.S. Food and Drug Administration, Silver Spring, MD, USA. Electronic address: carol.weiss@fda.hhs.gov.

Abstract

The rapid emergence of SARS-CoV-2 variants challenges vaccination strategies. Here, we collected 201 serum samples from persons with a single infection or multiple vaccine exposures, or both. We measured their neutralization titers against 15 natural variants and 7 variants with engineered spike mutations and analyzed antigenic diversity. Antigenic maps of primary infection sera showed that Omicron sublineages BA.2, BA.4/BA.5, and BA.2.12.1 are distinct from BA.1 and more similar to Beta/Gamma/Mu variants. Three mRNA COVID-19 vaccinations increased neutralization of BA.1 more than BA.4/BA.5 or BA.2.12.1. BA.1 post-vaccination infection elicited higher neutralization titers to all variants than three vaccinations alone, although with less neutralization to BA.2.12.1 and BA.4/BA.5. Those with BA.1 infection after two or three vaccinations had similar neutralization titer magnitude and antigenic recognition. Accounting for antigenic differences among variants when interpreting neutralization titers can aid the understanding of complex patterns in humoral immunity that informs the selection of future COVID-19 vaccine strains.

Keywords: COVID-19 vaccine; Omicron; SARS-CoV-2; SARS-CoV-2 variants; antigenic cartography; antigenic landscape; cartography; hybrid immunity; mRNA vaccine; spike.

Published by Elsevier Inc.

MeSH terms

Antibodies, Neutralizing
Antibodies, Viral
COVID-19 Vaccines*
COVID-19* / prevention & control
Humans
SARS-CoV-2 / genetics
Vaccination

Substances

COVID-19 Vaccines
Antibodies, Viral
Antibodies, Neutralizing

Supplementary concepts

SARS-CoV-2 variants

Grants and funding

Y01 AI005072/AI/NIAID NIH HHS/United States