tetano
Editor, Senior Moderator
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[SUP] 1 2 [/SUP], Barbara J Flynn[SUP] 1 2 [/SUP], Kathryn E Foulds[SUP] 1 2 [/SUP], Amy T Noe[SUP] 1 2 [/SUP], Anne P Werner[SUP] 1 2 [/SUP], Ian N Moore[SUP] 1 2 [/SUP], Matthew Gagne[SUP] 1 2 [/SUP], Timothy S Johnston[SUP] 1 2 [/SUP], Courtney Tucker[SUP] 1 2 [/SUP], Rachel L Davis[SUP] 1 2 [/SUP], Britta Flach[SUP] 1 2 2 [/SUP], Sarah O'Connell[SUP] 1 2 [/SUP], Shayne F Andrew[SUP] 1 2 [/SUP], Evan Lamb[SUP] 1 2 [/SUP], Dillon R Flebbe[SUP] 1 2 [/SUP], Saule T Nurmukhambetova[SUP] 3 2 [/SUP], Mitzi M Donaldson[SUP] 1 2 [/SUP], John-Paul M Todd[SUP] 1 2 [/SUP], Alex Lee Zhu[SUP] 4 5 1 4 [/SUP], Caroline Atyeo[SUP] 4 6 1 5 [/SUP], Stephanie Fischinger[SUP] 4 5 1 4 [/SUP], Matthew J Gorman[SUP] 4 1 [/SUP], Sally Shin[SUP] 4 1 [/SUP], Venkata Viswanadh Edara[SUP] 7 8 9 6 10 7 [/SUP], Katharine Floyd[SUP] 7 8 9 6 10 7 [/SUP], Lilin Lai[SUP] 7 8 9 6 10 7 [/SUP], Seyhan Boyoglu-Barnum[SUP] 1 2 [/SUP], Renee Van De Wetering[SUP] 1 2 [/SUP], Alida Taylor[SUP] 1 2 [/SUP], Elizabeth McCarthy[SUP] 1 2 [/SUP], Valerie Lecouturier[SUP] 11 8 [/SUP], Sophie Ruiz[SUP] 11 8 [/SUP], Catherine Berry[SUP] 11 12 8 [/SUP], Timothy Tibbitts[SUP] 12 9 [/SUP], Hanne Andersen[SUP] 13 11 [/SUP], Anthony Cook[SUP] 13 11 [/SUP], Alan Dodson[SUP] 13 11 [/SUP], Laurent Pessaint[SUP] 13 11 [/SUP], Alex Van Ry[SUP] 13 11 [/SUP], Marguerite Koutsoukos[SUP] 12 [/SUP], Cindy Gutzeit[SUP] 3 [/SUP], I-Ting Teng[SUP] 1 2 [/SUP], Tongqing Zhou[SUP] 1 2 [/SUP], Dapeng Li[SUP] 13 [/SUP], Barton F Haynes[SUP] 13 [/SUP], Peter D Kwong[SUP] 1 2 [/SUP], Adrian McDermott[SUP] 1 2 [/SUP], Mark G Lewis[SUP] 13 11 [/SUP], Tong Ming Fu[SUP] 12 9 [/SUP], Roman Chicz[SUP] 12 9 [/SUP], Robbert van der Most[SUP] 10 3 [/SUP], Kizzmekia S Corbett[SUP] 1 2 [/SUP], Mehul S Suthar[SUP] 7 8 9 6 10 7 [/SUP], Galit Alter[SUP] 4 1 [/SUP], Mario Roederer[SUP] 1 2 [/SUP], Nancy J Sullivan[SUP] 1 2 [/SUP], Daniel C Douek[SUP] 1 2 [/SUP], Barney S Graham[SUP] 1 2 [/SUP], Danilo Casimiro[SUP] 12 9 [/SUP], Robert A Seder[SUP] 14 2 [/SUP]
Affiliations
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 F[SUB]C[/SUB] receptors mediating immune cell effector functions in vitro. The neutralizing 50% inhibitory concentration (IC[SUB]50[/SUB]) 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 (3x10[SUP]6[/SUP] 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.
. 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[SUP] 1 2 [/SUP], Barbara J Flynn[SUP] 1 2 [/SUP], Kathryn E Foulds[SUP] 1 2 [/SUP], Amy T Noe[SUP] 1 2 [/SUP], Anne P Werner[SUP] 1 2 [/SUP], Ian N Moore[SUP] 1 2 [/SUP], Matthew Gagne[SUP] 1 2 [/SUP], Timothy S Johnston[SUP] 1 2 [/SUP], Courtney Tucker[SUP] 1 2 [/SUP], Rachel L Davis[SUP] 1 2 [/SUP], Britta Flach[SUP] 1 2 2 [/SUP], Sarah O'Connell[SUP] 1 2 [/SUP], Shayne F Andrew[SUP] 1 2 [/SUP], Evan Lamb[SUP] 1 2 [/SUP], Dillon R Flebbe[SUP] 1 2 [/SUP], Saule T Nurmukhambetova[SUP] 3 2 [/SUP], Mitzi M Donaldson[SUP] 1 2 [/SUP], John-Paul M Todd[SUP] 1 2 [/SUP], Alex Lee Zhu[SUP] 4 5 1 4 [/SUP], Caroline Atyeo[SUP] 4 6 1 5 [/SUP], Stephanie Fischinger[SUP] 4 5 1 4 [/SUP], Matthew J Gorman[SUP] 4 1 [/SUP], Sally Shin[SUP] 4 1 [/SUP], Venkata Viswanadh Edara[SUP] 7 8 9 6 10 7 [/SUP], Katharine Floyd[SUP] 7 8 9 6 10 7 [/SUP], Lilin Lai[SUP] 7 8 9 6 10 7 [/SUP], Seyhan Boyoglu-Barnum[SUP] 1 2 [/SUP], Renee Van De Wetering[SUP] 1 2 [/SUP], Alida Taylor[SUP] 1 2 [/SUP], Elizabeth McCarthy[SUP] 1 2 [/SUP], Valerie Lecouturier[SUP] 11 8 [/SUP], Sophie Ruiz[SUP] 11 8 [/SUP], Catherine Berry[SUP] 11 12 8 [/SUP], Timothy Tibbitts[SUP] 12 9 [/SUP], Hanne Andersen[SUP] 13 11 [/SUP], Anthony Cook[SUP] 13 11 [/SUP], Alan Dodson[SUP] 13 11 [/SUP], Laurent Pessaint[SUP] 13 11 [/SUP], Alex Van Ry[SUP] 13 11 [/SUP], Marguerite Koutsoukos[SUP] 12 [/SUP], Cindy Gutzeit[SUP] 3 [/SUP], I-Ting Teng[SUP] 1 2 [/SUP], Tongqing Zhou[SUP] 1 2 [/SUP], Dapeng Li[SUP] 13 [/SUP], Barton F Haynes[SUP] 13 [/SUP], Peter D Kwong[SUP] 1 2 [/SUP], Adrian McDermott[SUP] 1 2 [/SUP], Mark G Lewis[SUP] 13 11 [/SUP], Tong Ming Fu[SUP] 12 9 [/SUP], Roman Chicz[SUP] 12 9 [/SUP], Robbert van der Most[SUP] 10 3 [/SUP], Kizzmekia S Corbett[SUP] 1 2 [/SUP], Mehul S Suthar[SUP] 7 8 9 6 10 7 [/SUP], Galit Alter[SUP] 4 1 [/SUP], Mario Roederer[SUP] 1 2 [/SUP], Nancy J Sullivan[SUP] 1 2 [/SUP], Daniel C Douek[SUP] 1 2 [/SUP], Barney S Graham[SUP] 1 2 [/SUP], Danilo Casimiro[SUP] 12 9 [/SUP], Robert A Seder[SUP] 14 2 [/SUP]
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 F[SUB]C[/SUB] receptors mediating immune cell effector functions in vitro. The neutralizing 50% inhibitory concentration (IC[SUB]50[/SUB]) 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 (3x10[SUP]6[/SUP] 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.