tetano
Editor, Senior Moderator
N Engl J Med
. 2020 Jul 28.
doi: 10.1056/NEJMoa2024671. Online ahead of print.
Evaluation of the mRNA-1273 Vaccine against SARS-CoV-2 in Nonhuman Primates
Kizzmekia S Corbett[SUP] 1 [/SUP], Barbara Flynn[SUP] 1 [/SUP], Kathryn E Foulds[SUP] 1 [/SUP], Joseph R Francica[SUP] 1 [/SUP], Seyhan Boyoglu-Barnum[SUP] 1 [/SUP], Anne P Werner[SUP] 1 [/SUP], Britta Flach[SUP] 1 [/SUP], Sarah O'Connell[SUP] 1 [/SUP], Kevin W Bock[SUP] 1 [/SUP], Mahnaz Minai[SUP] 1 [/SUP], Bianca M Nagata[SUP] 1 [/SUP], Hanne Andersen[SUP] 1 [/SUP], David R Martinez[SUP] 1 [/SUP], Amy T Noe[SUP] 1 [/SUP], Naomi Douek[SUP] 1 [/SUP], Mitzi M Donaldson[SUP] 1 [/SUP], Nadesh N Nji[SUP] 1 [/SUP], Gabriela S Alvarado[SUP] 1 [/SUP], Darin K Edwards[SUP] 1 [/SUP], Dillon R Flebbe[SUP] 1 [/SUP], Evan Lamb[SUP] 1 [/SUP], Nicole A Doria-Rose[SUP] 1 [/SUP], Bob C Lin[SUP] 1 [/SUP], Mark K Louder[SUP] 1 [/SUP], Sijy O'Dell[SUP] 1 [/SUP], Stephen D Schmidt[SUP] 1 [/SUP], Emily Phung[SUP] 1 [/SUP], Lauren A Chang[SUP] 1 [/SUP], Christina Yap[SUP] 1 [/SUP], John-Paul M Todd[SUP] 1 [/SUP], Laurent Pessaint[SUP] 1 [/SUP], Alex Van Ry[SUP] 1 [/SUP], Shanai Browne[SUP] 1 [/SUP], Jack Greenhouse[SUP] 1 [/SUP], Tammy Putman-Taylor[SUP] 1 [/SUP], Amanda Strasbaugh[SUP] 1 [/SUP], Tracey-Ann Campbell[SUP] 1 [/SUP], Anthony Cook[SUP] 1 [/SUP], Alan Dodson[SUP] 1 [/SUP], Katelyn Steingrebe[SUP] 1 [/SUP], Wei Shi[SUP] 1 [/SUP], Yi Zhang[SUP] 1 [/SUP], Olubukola M Abiona[SUP] 1 [/SUP], Lingshu Wang[SUP] 1 [/SUP], Amarendra Pegu[SUP] 1 [/SUP], Eun Sung Yang[SUP] 1 [/SUP], Kwanyee Leung[SUP] 1 [/SUP], Tongqing Zhou[SUP] 1 [/SUP], I-Ting Teng[SUP] 1 [/SUP], Alicia Widge[SUP] 1 [/SUP], Ingelise Gordon[SUP] 1 [/SUP], Laura Novik[SUP] 1 [/SUP], Rebecca A Gillespie[SUP] 1 [/SUP], Rebecca J Loomis[SUP] 1 [/SUP], Juan I Moliva[SUP] 1 [/SUP], Guillaume Stewart-Jones[SUP] 1 [/SUP], Sunny Himansu[SUP] 1 [/SUP], Wing-Pui Kong[SUP] 1 [/SUP], Martha C Nason[SUP] 1 [/SUP], Kaitlyn M Morabito[SUP] 1 [/SUP], Tracy J Ruckwardt[SUP] 1 [/SUP], Julie E Ledgerwood[SUP] 1 [/SUP], Martin R Gaudinski[SUP] 1 [/SUP], Peter D Kwong[SUP] 1 [/SUP], John R Mascola[SUP] 1 [/SUP], Andrea Carfi[SUP] 1 [/SUP], Mark G Lewis[SUP] 1 [/SUP], Ralph S Baric[SUP] 1 [/SUP], Adrian McDermott[SUP] 1 [/SUP], Ian N Moore[SUP] 1 [/SUP], Nancy J Sullivan[SUP] 1 [/SUP], Mario Roederer[SUP] 1 [/SUP], Robert A Seder[SUP] 1 [/SUP], Barney S Graham[SUP] 1 [/SUP]
Affiliations
Abstract
Background: Vaccines to prevent coronavirus disease 2019 (Covid-19) are urgently needed. The effect of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccines on viral replication in both upper and lower airways is important to evaluate in nonhuman primates.
Methods: Nonhuman primates received 10 or 100 μg of mRNA-1273, a vaccine encoding the prefusion-stabilized spike protein of SARS-CoV-2, or no vaccine. Antibody and T-cell responses were assessed before upper- and lower-airway challenge with SARS-CoV-2. Active viral replication and viral genomes in bronchoalveolar-lavage (BAL) fluid and nasal swab specimens were assessed by polymerase chain reaction, and histopathological analysis and viral quantification were performed on lung-tissue specimens.
Results: The mRNA-1273 vaccine candidate induced antibody levels exceeding those in human convalescent-phase serum, with live-virus reciprocal 50% inhibitory dilution (ID[SUB]50[/SUB]) geometric mean titers of 501 in the 10-μg dose group and 3481 in the 100-μg dose group. Vaccination induced type 1 helper T-cell (Th1)-biased CD4 T-cell responses and low or undetectable Th2 or CD8 T-cell responses. Viral replication was not detectable in BAL fluid by day 2 after challenge in seven of eight animals in both vaccinated groups. No viral replication was detectable in the nose of any of the eight animals in the 100-μg dose group by day 2 after challenge, and limited inflammation or detectable viral genome or antigen was noted in lungs of animals in either vaccine group.
Conclusions: Vaccination of nonhuman primates with mRNA-1273 induced robust SARS-CoV-2 neutralizing activity, rapid protection in the upper and lower airways, and no pathologic changes in the lung. (Funded by the National Institutes of Health and others.).
. 2020 Jul 28.
doi: 10.1056/NEJMoa2024671. Online ahead of print.
Evaluation of the mRNA-1273 Vaccine against SARS-CoV-2 in Nonhuman Primates
Kizzmekia S Corbett[SUP] 1 [/SUP], Barbara Flynn[SUP] 1 [/SUP], Kathryn E Foulds[SUP] 1 [/SUP], Joseph R Francica[SUP] 1 [/SUP], Seyhan Boyoglu-Barnum[SUP] 1 [/SUP], Anne P Werner[SUP] 1 [/SUP], Britta Flach[SUP] 1 [/SUP], Sarah O'Connell[SUP] 1 [/SUP], Kevin W Bock[SUP] 1 [/SUP], Mahnaz Minai[SUP] 1 [/SUP], Bianca M Nagata[SUP] 1 [/SUP], Hanne Andersen[SUP] 1 [/SUP], David R Martinez[SUP] 1 [/SUP], Amy T Noe[SUP] 1 [/SUP], Naomi Douek[SUP] 1 [/SUP], Mitzi M Donaldson[SUP] 1 [/SUP], Nadesh N Nji[SUP] 1 [/SUP], Gabriela S Alvarado[SUP] 1 [/SUP], Darin K Edwards[SUP] 1 [/SUP], Dillon R Flebbe[SUP] 1 [/SUP], Evan Lamb[SUP] 1 [/SUP], Nicole A Doria-Rose[SUP] 1 [/SUP], Bob C Lin[SUP] 1 [/SUP], Mark K Louder[SUP] 1 [/SUP], Sijy O'Dell[SUP] 1 [/SUP], Stephen D Schmidt[SUP] 1 [/SUP], Emily Phung[SUP] 1 [/SUP], Lauren A Chang[SUP] 1 [/SUP], Christina Yap[SUP] 1 [/SUP], John-Paul M Todd[SUP] 1 [/SUP], Laurent Pessaint[SUP] 1 [/SUP], Alex Van Ry[SUP] 1 [/SUP], Shanai Browne[SUP] 1 [/SUP], Jack Greenhouse[SUP] 1 [/SUP], Tammy Putman-Taylor[SUP] 1 [/SUP], Amanda Strasbaugh[SUP] 1 [/SUP], Tracey-Ann Campbell[SUP] 1 [/SUP], Anthony Cook[SUP] 1 [/SUP], Alan Dodson[SUP] 1 [/SUP], Katelyn Steingrebe[SUP] 1 [/SUP], Wei Shi[SUP] 1 [/SUP], Yi Zhang[SUP] 1 [/SUP], Olubukola M Abiona[SUP] 1 [/SUP], Lingshu Wang[SUP] 1 [/SUP], Amarendra Pegu[SUP] 1 [/SUP], Eun Sung Yang[SUP] 1 [/SUP], Kwanyee Leung[SUP] 1 [/SUP], Tongqing Zhou[SUP] 1 [/SUP], I-Ting Teng[SUP] 1 [/SUP], Alicia Widge[SUP] 1 [/SUP], Ingelise Gordon[SUP] 1 [/SUP], Laura Novik[SUP] 1 [/SUP], Rebecca A Gillespie[SUP] 1 [/SUP], Rebecca J Loomis[SUP] 1 [/SUP], Juan I Moliva[SUP] 1 [/SUP], Guillaume Stewart-Jones[SUP] 1 [/SUP], Sunny Himansu[SUP] 1 [/SUP], Wing-Pui Kong[SUP] 1 [/SUP], Martha C Nason[SUP] 1 [/SUP], Kaitlyn M Morabito[SUP] 1 [/SUP], Tracy J Ruckwardt[SUP] 1 [/SUP], Julie E Ledgerwood[SUP] 1 [/SUP], Martin R Gaudinski[SUP] 1 [/SUP], Peter D Kwong[SUP] 1 [/SUP], John R Mascola[SUP] 1 [/SUP], Andrea Carfi[SUP] 1 [/SUP], Mark G Lewis[SUP] 1 [/SUP], Ralph S Baric[SUP] 1 [/SUP], Adrian McDermott[SUP] 1 [/SUP], Ian N Moore[SUP] 1 [/SUP], Nancy J Sullivan[SUP] 1 [/SUP], Mario Roederer[SUP] 1 [/SUP], Robert A Seder[SUP] 1 [/SUP], Barney S Graham[SUP] 1 [/SUP]
Affiliations
- PMID: 32722908
- DOI: 10.1056/NEJMoa2024671
Abstract
Background: Vaccines to prevent coronavirus disease 2019 (Covid-19) are urgently needed. The effect of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccines on viral replication in both upper and lower airways is important to evaluate in nonhuman primates.
Methods: Nonhuman primates received 10 or 100 μg of mRNA-1273, a vaccine encoding the prefusion-stabilized spike protein of SARS-CoV-2, or no vaccine. Antibody and T-cell responses were assessed before upper- and lower-airway challenge with SARS-CoV-2. Active viral replication and viral genomes in bronchoalveolar-lavage (BAL) fluid and nasal swab specimens were assessed by polymerase chain reaction, and histopathological analysis and viral quantification were performed on lung-tissue specimens.
Results: The mRNA-1273 vaccine candidate induced antibody levels exceeding those in human convalescent-phase serum, with live-virus reciprocal 50% inhibitory dilution (ID[SUB]50[/SUB]) geometric mean titers of 501 in the 10-μg dose group and 3481 in the 100-μg dose group. Vaccination induced type 1 helper T-cell (Th1)-biased CD4 T-cell responses and low or undetectable Th2 or CD8 T-cell responses. Viral replication was not detectable in BAL fluid by day 2 after challenge in seven of eight animals in both vaccinated groups. No viral replication was detectable in the nose of any of the eight animals in the 100-μg dose group by day 2 after challenge, and limited inflammation or detectable viral genome or antigen was noted in lungs of animals in either vaccine group.
Conclusions: Vaccination of nonhuman primates with mRNA-1273 induced robust SARS-CoV-2 neutralizing activity, rapid protection in the upper and lower airways, and no pathologic changes in the lung. (Funded by the National Institutes of Health and others.).