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

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 (ID50) 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.)

Tradeoffs between income, biodiversity, and ecosystem functioning during tropical rainforest conversion and agroforestry intensification

Losses of biodiversity and ecosystem functioning due to rainforest destruction and agricultural intensification are prime concerns for science and society alike. Potentially, ecosystems show nonlinear responses to land-use intensification that would open management options with limited ecological losses but satisfying economic gains. However, multidisciplinary studies to quantify ecological losses and socioeconomic tradeoffs under different management options are rare. Here, we evaluate opposing land use strategies in cacao agroforestry in Sulawesi, Indonesia, by using data on species richness of nine plant and animal taxa, six related ecosystem functions, and on socioeconomic drivers of agroforestry expansion. Expansion of cacao cultivation by 230% in the last two decades was triggered not only by economic market mechanisms, but also by rarely considered cultural factors. Transformation from near-primary forest to agroforestry had little effect on overall species richness, but reduced plant biomass and carbon storage by ≈75% and species richness of forest-using species by ≈60%. In contrast, increased land use intensity in cacao agroforestry, coupled with a reduction in shade tree cover from 80% to 40%, caused only minor quantitative changes in biodiversity and maintained high levels of ecosystem functioning while doubling farmers' net income. However, unshaded systems further increased income by ≈40%, implying that current economic incentives and cultural preferences for new intensification practices put shaded systems at risk. We conclude that low-shade agroforestry provides the best available compromise between economic forces and ecological needs. Certification schemes for shade-grown crops may provide a market-based mechanism to slow down current intensification trends