Mapping SARS-CoV-2 antigenic relationships and serological responses
Samuel Wilks, Barbara Mühlemann, Xiaoying Shen, Sina Türeli, Eric B. LeGresley, Antonia Netzl, Miguela A. Caniza, Jesus N. Chacaltana-Huarcaya, Victor M. Corman, Xiaoju Daniell, Michael Datto, Fatimah S. Dawood, Thomas N. Denny, Christian Drosten, Ron A. M. Fouchier, Patricia García, Peter Halfmann, Agatha N. Jassem, Lara M. Jeworowski, Terry C. Jones, Yoshihiro Kawaoka, Florian Krammer, Charlene McDanal, Rolando Pajón, Viviana Simon, Melissa S. Stockwell, Haili Tang, Harm van Bakel, Vic Veguilla, Richard J. Webby, David C. Montefiori, Derek J. Smith
Abstract
During the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic, multiple variants escaping preexisting immunity emerged, causing reinfections of previously exposed individuals. Here, we used antigenic cartography to analyze patterns of cross-reactivity among 21 variants and 15 groups of human sera obtained after primary infection with 10 different variants or after messenger RNA (mRNA)-1273 or mRNA-1273.351 vaccination. We found antigenic differences among pre-Omicron variants caused by substitutions at spike-protein positions 417, 452, 484, and 501. Quantifying changes in response breadth over time and with additional vaccine doses, our results show the largest increase between 4 weeks and >3 months after a second dose. We found changes in immunodominance of different spike regions, depending on the variant an individual was first exposed to, with implications for variant risk assessment and vaccine-strain selection.