Hanné Andersen

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: ) 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.).

Prototype DNA vaccines for SARS-CoV-2 The development of a vaccine to protect against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is an urgent biomedical need. Yu et al. designed a series of prototype DNA vaccines against the SARS-CoV-2 spike protein, which is used by the virus to bind and invade human cells. Analysis of the vaccine candidates in rhesus macaques showed that animals developed protective humoral and cellular immune responses when challenged with the virus. Neutralizing antibody titers were also observed at levels similar to those seen in humans who have recovered from SARS-CoV-2 infection. Science , this issue p. 806

Immunity from reinfection One of the many open questions about severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is whether an individual who has cleared the virus can be infected a second time and get sick. Chandrashekar et al. and Deng et al. generated rhesus macaque models of SARS-CoV-2 infection and tested whether natural SARS-CoV-2 infection could result in immunity to viral rechallenge. They found that animals indeed developed immune responses that protected against a second infection. Although there are differences between SARS-CoV-2 infection in macaques and in humans, these findings have key implications for public health and economic initiatives if validated in human studies. Science , this issue p. 812 , p. 818