ABSTRACT
mRNA-1273 vaccine efficacy against SARS-CoV-2 Delta wanes over time; however, there are limited data on the impact of durability of immune responses on protection. We immunized rhesus macaques at weeks 0 and 4 and assessed immune responses over one year in blood, upper and lower airways. Serum neutralizing titers to Delta were 280 and 34 reciprocal ID50 at weeks 6 (peak) and 48 (challenge), respectively. Antibody binding titers also decreased in bronchoalveolar lavage (BAL). Four days after challenge, virus was unculturable in BAL and subgenomic RNA declined ∼3-log10 compared to control animals. In nasal swabs, sgRNA declined 1-log10 and virus remained culturable. Anamnestic antibody responses (590-fold increase) but not T cell responses were detected in BAL by day 4 post-challenge. mRNA-1273-mediated protection in the lungs is durable but delayed and potentially dependent on anamnestic antibody responses. Rapid and sustained protection in upper and lower airways may eventually require a boost.
Competing Interest Statement
K.S.C. and B.S.G. are inventors on U.S. Patent No. 10,960,070 B2 and International Patent Application No. WO/2018/081318 entitled Prefusion Coronavirus Spike Proteins and Their Use. K.S.C. and B.S.G. are inventors on U.S. Patent Application No. 62/972,886 entitled 2019-nCoV Vaccine. L.W., E.S.Y., W.S., J.R.M., M.R., N.J.S. and D.C.D are inventors on U.S. Patent Application No. 63/147,419 entitled Antibodies Targeting the Spike Protein of Coronaviruses. L.P., A.C., A.D., A.G., S.K., H.A. and M.G.L. are employees of Bioqual. K.S.C, L.W., W.S. and B.S.G are inventors on multiple U.S. Patent Applications entitled Anti-Coronavirus Antibodies and Methods of Use. A.C. and D.K.E. are employees of Moderna. M.S.S. serves on the scientific board of advisors for Moderna. The other authors declare no competing interests.
