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 SmithTahaniyat 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*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

25 Scopus citations


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.

Original languageEnglish
Pages (from-to)1745-1758.e7
JournalCell Host and Microbe
Issue number12
StatePublished - 14 Dec 2022
Externally publishedYes


  • COVID-19 vaccine
  • Omicron
  • SARS-CoV-2
  • SARS-CoV-2 variants
  • antigenic cartography
  • antigenic landscape
  • cartography
  • hybrid immunity
  • mRNA vaccine
  • spike


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