Sci Transl Med
. 2021 Jul 27;eabi4547.
doi: 10.1126/scitranslmed.abi4547. Online ahead of print.
Protective antibodies elicited by SARS-CoV-2 spike protein vaccination are boosted in the lung after challenge in nonhuman primates
Joseph R Francica 1 2 , Barbara J Flynn 1 2 , Kathryn E Foulds 1 2 , Amy T Noe 1 2 , Anne P Werner 1 2 , Ian N Moore 1 2 , Matthew Gagne 1 2 , Timothy S Johnston 1 2 , Courtney Tucker 1 2 , Rachel L Davis 1 2 , Britta Flach 1 2 2 , Sarah O'Connell 1 2 , Shayne F Andrew 1 2 , Evan Lamb 1 2 , Dillon R Flebbe 1 2 , Saule T Nurmukhambetova 3 2 , Mitzi M Donaldson 1 2 , John-Paul M Todd 1 2 , Alex Lee Zhu 4 5 1 4 , Caroline Atyeo 4 6 1 5 , Stephanie Fischinger 4 5 1 4 , Matthew J Gorman 4 1 , Sally Shin 4 1 , Venkata Viswanadh Edara 7 8 9 6 10 7 , Katharine Floyd 7 8 9 6 10 7 , Lilin Lai 7 8 9 6 10 7 , Seyhan Boyoglu-Barnum 1 2 , Renee Van De Wetering 1 2 , Alida Taylor 1 2 , Elizabeth McCarthy 1 2 , Valerie Lecouturier 11 8 , Sophie Ruiz 11 8 , Catherine Berry 11 12 8 , Timothy Tibbitts 12 9 , Hanne Andersen 13 11 , Anthony Cook 13 11 , Alan Dodson 13 11 , Laurent Pessaint 13 11 , Alex Van Ry 13 11 , Marguerite Koutsoukos 12 , Cindy Gutzeit 3 , I-Ting Teng 1 2 , Tongqing Zhou 1 2 , Dapeng Li 13 , Barton F Haynes 13 , Peter D Kwong 1 2 , Adrian McDermott 1 2 , Mark G Lewis 13 11 , Tong Ming Fu 12 9 , Roman Chicz 12 9 , Robbert van der Most 10 3 , Kizzmekia S Corbett 1 2 , Mehul S Suthar 7 8 9 6 10 7 , Galit Alter 4 1 , Mario Roederer 1 2 , Nancy J Sullivan 1 2 , Daniel C Douek 1 2 , Barney S Graham 1 2 , Danilo Casimiro 12 9 , Robert A Seder 14 2
Affiliations
- PMID: 34315825
- DOI: 10.1126/scitranslmed.abi4547
Abstract
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 (NHP). Binding and functional neutralization assays and systems serology revealed that the vaccinated NHP developed AS03-dependent multi-functional 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 (IC50) titers for pseudovirus and live SARS-CoV-2 were higher than titers for a panel of human convalescent serum samples. NHP were challenged intranasally and intratracheally with a high dose (3x106 plaque forming units, PFU) of SARS-CoV-2 (USA-WA1/2020 isolate). Two days post-challenge, vaccinated NHP showed rapid control of viral replication in both the upper and lower airways. Notably, vaccinated NHP also had increased spike protein-specific IgG antibody responses in the lung as early as two days post 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 NHP and that rapid anamnestic antibody responses in the lung may be a key mechanism for protection.