Protective antibodies elicited by SARS-CoV-2 spike protein vaccination are boosted in the lung after challenge in nonhuman primates

Joseph R. Francica, Barbara J. Flynn, Kathryn E. Foulds, Amy T. Noe, Anne P. Werner, Ian N. Moore, Matthew Gagne, Timothy S. Johnston, Courtney Tucker, Rachel L. Davis, Britta Flach, Sarah O'Connell, Shayne F. Andrew, Evan Lamb, Dillon R. Flebbe, Saule T. Nurmukhambetova, Mitzi M. Donaldson, John Paul M. Todd, Alex Lee Zhu, Caroline AtyeoStephanie Fischinger, Matthew J. Gorman, Sally Shin, Venkata Viswanadh Edara, Katharine Floyd, Lilin Lai, Seyhan Boyoglu-Barnum, Renee Van De Wetering, Alida Tylor, Elizabeth McCarthy, Valerie Lecouturier, Sophie Ruiz, Catherine Berry, Timothy Tibbitts, Hanne Andersen, Anthony Cook, Alan Dodson, Laurent Pessaint, Alex Van Ry, Marguerite Koutsoukos, Cindy Gutzeit, I. Ting Teng, Tongqing Zhou, Dapeng Li, Barton F. Haynes, Peter D. Kwong, Adrian McDermott, Mark G. Lewis, Tong Ming Fu, Roman Chicz, Robbert Van der Most, Kizzmekia S. Corbett, Mehul S. Suthar, Galit Alter, Mario Roederer, Nancy J. Sullivan, Daniel C. Douek, Barney S. Graham, Danilo Casimiro, Robert A. Seder

Research output: Contribution to journalArticlepeer-review

35 Scopus citations


Adjuvanted soluble protein vaccines have been used extensively in humans for protection against various viral infections based on their robust induction of antibody responses. Here, soluble prefusion-stabilized spike protein trimers (preS dTM) from severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) were formulated with the adjuvant AS03 and administered twice to nonhuman primates (NHPs). Binding and functional neutralization assays and systems serology revealed that the vaccinated NHP developed AS03-dependent multifunctional humoral responses that targeted distinct domains of the spike protein and bound to a variety of Fc receptors mediating immune cell effector functions in vitro. The neutralizing 50% inhibitory concentration titers for pseudovirus and live SARS-CoV-2 were higher than titers for a panel of human convalescent serum samples. NHPs were challenged intranasally and intratracheally with a high dose (3 × 106 plaque forming units) of SARS-CoV-2 (USA-WA1/2020 isolate). Two days after challenge, vaccinated NHPs showed rapid control of viral replication in both the upper and lower airways. Vaccinated NHPs also had increased spike protein-specific immunoglobulin G (IgG) antibody responses in the lung as early as 2 days after challenge. Moreover, passive transfer of vaccine-induced IgG to hamsters mediated protection from subsequent SARS-CoV-2 challenge. These data show that antibodies induced by the AS03-adjuvanted preS dTM vaccine were sufficient to mediate protection against SARS-CoV-2 in NHPs and that rapid anamnestic antibody responses in the lung may be a key mechanism for protection.

Original languageEnglish
Article numbereabi4547
JournalScience Translational Medicine
Issue number607
StatePublished - 18 Aug 2021
Externally publishedYes


Dive into the research topics of 'Protective antibodies elicited by SARS-CoV-2 spike protein vaccination are boosted in the lung after challenge in nonhuman primates'. Together they form a unique fingerprint.

Cite this