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Deprecated: Implicit conversion from float 231.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 N+Engl+J+Med 2020 ; 383 (16): 1544-1555 Nephropedia Template TP
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Evaluation of the mRNA-1273 Vaccine against SARS-CoV-2 in Nonhuman Primates #MMPMID32722908
Corbett KS; Flynn B; Foulds KE; Francica JR; Boyoglu-Barnum S; Werner AP; Flach B; O'Connell S; Bock KW; Minai M; Nagata BM; Andersen H; Martinez DR; Noe AT; Douek N; Donaldson MM; Nji NN; Alvarado GS; Edwards DK; Flebbe DR; Lamb E; Doria-Rose NA; Lin BC; Louder MK; O'Dell S; Schmidt SD; Phung E; Chang LA; Yap C; Todd JM; Pessaint L; Van Ry A; Browne S; Greenhouse J; Putman-Taylor T; Strasbaugh A; Campbell TA; Cook A; Dodson A; Steingrebe K; Shi W; Zhang Y; Abiona OM; Wang L; Pegu A; Yang ES; Leung K; Zhou T; Teng IT; Widge A; Gordon I; Novik L; Gillespie RA; Loomis RJ; Moliva JI; Stewart-Jones G; Himansu S; Kong WP; Nason MC; Morabito KM; Ruckwardt TJ; Ledgerwood JE; Gaudinski MR; Kwong PD; Mascola JR; Carfi A; Lewis MG; Baric RS; McDermott A; Moore IN; Sullivan NJ; Roederer M; Seder RA; Graham BS
N Engl J Med 2020[Oct]; 383 (16): 1544-1555 PMID32722908show ga
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 mug 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(50)) geometric mean titers of 501 in the 10-mug dose group and 3481 in the 100-mug 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-mug 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.).