Protection from SARS-CoV-2 Delta one year after mRNA-1273 vaccination in rhesus macaques coincides with anamnestic antibody response in the lung

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. Here, we immunized rhesus macaques and assessed immune responses over 1 year in blood and 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 Delta challenge, the virus was unculturable in BAL, and subgenomic RNA declined by ∼3-log10 compared with control animals. In nasal swabs, sgRNA was reduced by 1-log10, and the virus remained culturable. Anamnestic antibodies (590-fold increased titer) 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. [Display omitted] •Protection from severe lung disease 1 year after mRNA-1273 vaccination in macaques•Protection in the lungs is coincident with a local anamnestic antibody response•Protection in upper airway is limited 1 year after mRNA-1273 vaccination•Neutralizing responses to Delta are low to undetectable 1 year after mRNA-1273 vaccination A study looking at immunity against the SARS-CoV-2 Delta variant one year after mRNA vaccination found durable but delayed anamnestic antibody responses in the lung but limited protection in the upper airway and low neutralizing responses, thus advocating for booster shots for sustained upper and lower airway protection.