mRNA-1273 or mRNA-Omicron boost in vaccinated macaques elicits similar B cell expansion, neutralizing responses, and protection from Omicron

• Published in: Cell Vol. 185; no. 9; pp. 1556 - 1571.e18
• Main Authors: Gagne, Matthew, Moliva, Juan I., Foulds, Kathryn E., Andrew, Shayne F., Flynn, Barbara J., Werner, Anne P., Wagner, Danielle A., Teng, I-Ting, Lin, Bob C., Moore, Christopher, Jean-Baptiste, Nazaire, Carroll, Robin, Foster, Stephanie L., Patel, Mit, Ellis, Madison, Edara, Venkata-Viswanadh, Maldonado, Nahara Vargas, Minai, Mahnaz, McCormick, Lauren, Honeycutt, Christopher Cole, Nagata, Bianca M., Bock, Kevin W., Dulan, Caitlyn N.M., Cordon, Jamilet, Flebbe, Dillon R., Todd, John-Paul M., McCarthy, Elizabeth, Pessaint, Laurent, Van Ry, Alex, Narvaez, Brandon, Valentin, Daniel, Cook, Anthony, Dodson, Alan, Steingrebe, Katelyn, Nurmukhambetova, Saule T., Godbole, Sucheta, Henry, Amy R., Laboune, Farida, Roberts-Torres, Jesmine, Lorang, Cynthia G., Amin, Shivani, Trost, Jessica, Naisan, Mursal, Basappa, Manjula, Willis, Jacquelyn, Wang, Lingshu, Shi, Wei, Doria-Rose, Nicole A., Zhang, Yi, Yang, Eun Sung, Leung, Kwanyee, O’Dell, Sijy, Schmidt, Stephen D., Olia, Adam S., Liu, Cuiping, Harris, Darcy R., Chuang, Gwo-Yu, Stewart-Jones, Guillaume, Renzi, Isabella, Lai, Yen-Ting, Malinowski, Agata, Wu, Kai, Mascola, John R., Carfi, Andrea, Kwong, Peter D., Edwards, Darin K., Lewis, Mark G., Andersen, Hanne, Corbett, Kizzmekia S., Nason, Martha C., McDermott, Adrian B., Suthar, Mehul S., Moore, Ian N., Roederer, Mario, Sullivan, Nancy J., Douek, Daniel C., Seder, Robert A.
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 28.04.2022; Cell Press
• Subjects: 2019-nCoV Vaccine mRNA-1273; Animals; Antibodies, Neutralizing; Antibodies, Viral; antibody; B cells; B-lymphocytes; boost; COVID-19; COVID-19 - prevention & control; immune memory; immunity; immunization; Macaca; mRNA vaccine; neutralization; Omicron; original antigenic sin; RNA, Messenger; SARS-CoV-2; Severe acute respiratory syndrome coronavirus 2; T cells; virus replication; COVID-19; original antigenic sin; SARS-CoV-2; antibody; immune memory; boost; Omicron; B cells; T cells; mRNA vaccine
• ISSN: 0092-8674; 1097-4172; 1097-4172
• DOI: 10.1016/j.cell.2022.03.038

SARS-CoV-2 Omicron is highly transmissible and has substantial resistance to neutralization following immunization with ancestral spike-matched vaccines. It is unclear whether boosting with Omicron-matched vaccines would enhance protection. Here, nonhuman primates that received mRNA-1273 at weeks 0 and 4 were boosted at week 41 with mRNA-1273 or mRNA-Omicron. Neutralizing titers against D614G were 4,760 and 270 reciprocal ID50 at week 6 (peak) and week 41 (preboost), respectively, and 320 and 110 for Omicron. 2 weeks after the boost, titers against D614G and Omicron increased to 5,360 and 2,980 for mRNA-1273 boost and 2,670 and 1,930 for mRNA-Omicron, respectively. Similar increases against BA.2 were observed. Following either boost, 70%–80% of spike-specific B cells were cross-reactive against WA1 and Omicron. Equivalent control of virus replication in lower airways was observed following Omicron challenge 1 month after either boost. These data show that mRNA-1273 and mRNA-Omicron elicit comparable immunity and protection shortly after the boost. [Display omitted] •mRNA-1273 prime induces cross-reactive B cells to Omicron and ancestral strains•Boosting with mRNA-1273 or mRNA-Omicron enhances neutralization of Omicron•Either boost expands B cells cross-reactive to Omicron and ancestral strains•mRNA-1273 or mRNA-Omicron boost is protective against Omicron replication in the lungs Boosting previously vaccinated nonhuman primates with either the mRNA-1273 or mRNA-Omicron vaccine expands cross-reactive memory B cells and elicits similar levels of protection upon challenge with SARS-CoV-2 Omicron.