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Evaluation of the mRNA-1273 Vaccine against SARS-CoV-2 in Nonhuman Primates.

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 ?g 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 (ID50) geometric mean titers of 501 in the 10-?g dose group and 3481 in the 100-?g 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-?g 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.).

SUBMITTER: Corbett KS

PROVIDER: S-EPMC7449230 | biostudies-literature | 2020 Oct

REPOSITORIES: biostudies-literature

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Evaluation of the mRNA-1273 Vaccine against SARS-CoV-2 in Nonhuman Primates.

Corbett Kizzmekia S KS Flynn Barbara B Foulds Kathryn E KE Francica Joseph R JR Boyoglu-Barnum Seyhan S Werner Anne P AP Flach Britta B O'Connell Sarah S Bock Kevin W KW Minai Mahnaz M Nagata Bianca M BM Andersen Hanne H Martinez David R DR Noe Amy T AT Douek Naomi N Donaldson Mitzi M MM Nji Nadesh N NN Alvarado Gabriela S GS Edwards Darin K DK Flebbe Dillon R DR Lamb Evan E Doria-Rose Nicole A NA Lin Bob C BC Louder Mark K MK O'Dell Sijy S Schmidt Stephen D SD Phung Emily E Chang Lauren A LA Yap Christina C Todd John-Paul M JM Pessaint Laurent L Van Ry Alex A Browne Shanai S Greenhouse Jack J Putman-Taylor Tammy T Strasbaugh Amanda A Campbell Tracey-Ann TA Cook Anthony A Dodson Alan A Steingrebe Katelyn K Shi Wei W Zhang Yi Y Abiona Olubukola M OM Wang Lingshu L Pegu Amarendra A Yang Eun Sung ES Leung Kwanyee K Zhou Tongqing T Teng I-Ting IT Widge Alicia A Gordon Ingelise I Novik Laura L Gillespie Rebecca A RA Loomis Rebecca J RJ Moliva Juan I JI Stewart-Jones Guillaume G Himansu Sunny S Kong Wing-Pui WP Nason Martha C MC Morabito Kaitlyn M KM Ruckwardt Tracy J TJ Ledgerwood Julie E JE Gaudinski Martin R MR Kwong Peter D PD Mascola John R JR Carfi Andrea A Lewis Mark G MG Baric Ralph S RS McDermott Adrian A Moore Ian N IN Sullivan Nancy J NJ Roederer Mario M Seder Robert A RA Graham Barney S BS

The New England journal of medicine 20200728 16

<h4>Background</h4>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.<h4>Methods</h4>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 l ...[more]

PMID: 32722908

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Project description:BackgroundThe incidence of coronavirus disease 2019 (Covid-19) among adolescents between 12 and 17 years of age was approximately 900 per 100,000 population from April 1 through June 11, 2021. The safety, immunogenicity, and efficacy of the mRNA-1273 vaccine in adolescents are unknown.MethodsIn this ongoing phase 2-3, placebo-controlled trial, we randomly assigned healthy adolescents (12 to 17 years of age) in a 2:1 ratio to receive two injections of the mRNA-1273 vaccine (100 μg in each) or placebo, administered 28 days apart. The primary objectives were evaluation of the safety of mRNA-1273 in adolescents and the noninferiority of the immune response in adolescents as compared with that in young adults (18 to 25 years of age) in a phase 3 trial. Secondary objectives included the efficacy of mRNA-1273 in preventing Covid-19 or asymptomatic severe acute respiratory syndrome coronavirus 2 infection.ResultsA total of 3732 participants were randomly assigned to receive mRNA-1273 (2489 participants) or placebo (1243 participants). In the mRNA-1273 group, the most common solicited adverse reactions after the first or second injections were injection-site pain (in 93.1% and 92.4%, respectively), headache (in 44.6% and 70.2%, respectively), and fatigue (in 47.9% and 67.8%, respectively); in the placebo group, the most common solicited adverse reactions after the first or second injections were injection-site pain (in 34.8% or 30.3%, respectively), headache (in 38.5% and 30.2%, respectively), and fatigue (in 36.6% and 28.9%, respectively). No serious adverse events related to mRNA-1273 or placebo were noted. The geometric mean titer ratio of pseudovirus neutralizing antibody titers in adolescents relative to young adults was 1.08 (95% confidence interval [CI], 0.94 to 1.24), and the absolute difference in serologic response was 0.2 percentage points (95% CI, -1.8 to 2.4), which met the noninferiority criterion. No cases of Covid-19 with an onset of 14 days after the second injection were reported in the mRNA-1273 group, and four cases occurred in the placebo group.ConclusionsThe mRNA-1273 vaccine had an acceptable safety profile in adolescents. The immune response was similar to that in young adults, and the vaccine was efficacious in preventing Covid-19. (Funded by Moderna and the Biomedical Advanced Research and Development Authority; Teen COVE ClinicalTrials.gov number, NCT04649151.).

Project description:BackgroundVaccines are needed to prevent coronavirus disease 2019 (Covid-19) and to protect persons who are at high risk for complications. The mRNA-1273 vaccine is a lipid nanoparticle-encapsulated mRNA-based vaccine that encodes the prefusion stabilized full-length spike protein of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the virus that causes Covid-19.MethodsThis phase 3 randomized, observer-blinded, placebo-controlled trial was conducted at 99 centers across the United States. Persons at high risk for SARS-CoV-2 infection or its complications were randomly assigned in a 1:1 ratio to receive two intramuscular injections of mRNA-1273 (100 μg) or placebo 28 days apart. The primary end point was prevention of Covid-19 illness with onset at least 14 days after the second injection in participants who had not previously been infected with SARS-CoV-2.ResultsThe trial enrolled 30,420 volunteers who were randomly assigned in a 1:1 ratio to receive either vaccine or placebo (15,210 participants in each group). More than 96% of participants received both injections, and 2.2% had evidence (serologic, virologic, or both) of SARS-CoV-2 infection at baseline. Symptomatic Covid-19 illness was confirmed in 185 participants in the placebo group (56.5 per 1000 person-years; 95% confidence interval [CI], 48.7 to 65.3) and in 11 participants in the mRNA-1273 group (3.3 per 1000 person-years; 95% CI, 1.7 to 6.0); vaccine efficacy was 94.1% (95% CI, 89.3 to 96.8%; P<0.001). Efficacy was similar across key secondary analyses, including assessment 14 days after the first dose, analyses that included participants who had evidence of SARS-CoV-2 infection at baseline, and analyses in participants 65 years of age or older. Severe Covid-19 occurred in 30 participants, with one fatality; all 30 were in the placebo group. Moderate, transient reactogenicity after vaccination occurred more frequently in the mRNA-1273 group. Serious adverse events were rare, and the incidence was similar in the two groups.ConclusionsThe mRNA-1273 vaccine showed 94.1% efficacy at preventing Covid-19 illness, including severe disease. Aside from transient local and systemic reactions, no safety concerns were identified. (Funded by the Biomedical Advanced Research and Development Authority and the National Institute of Allergy and Infectious Diseases; COVE ClinicalTrials.gov number, NCT04470427.).

Dataset Information

Evaluation of the mRNA-1273 Vaccine against SARS-CoV-2 in Nonhuman Primates.

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Evaluation of the mRNA-1273 Vaccine against SARS-CoV-2 in Nonhuman Primates.

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