Neutralizing antibody responses gradually wane against several variants of concern (VOCs) after vaccination with the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccine messenger RNA-1273 (mRNA-1273. We evaluated the immune responses in nonhuman primates that received a primary vaccination series of mRNA-1273 and were boosted about 6 months later with either homologous mRNA-1273 or heterologous mRNA-1273.b, which encompasses the spike sequence of the B.1.351 Beta variant. After boost, animals had increased neutralizing antibody responses across all VOCs, which was sustained for at least 8 weeks after boost. Nine weeks after boost, animals were challenged with the SARS-CoV-2 Beta variant. Viral replication was low to undetectable in bronchoalveolar lavage and significantly reduced in nasal swabs in all boosted animals, suggesting that booster vaccinations may be required to sustain immunity and protection.

B.1.351 is the SARS-CoV-2 variant most resistant to antibody neutralization. We demonstrate how the dose and number of immunizations influence protection. Nonhuman primates (NHP) received two doses of 30 or 100 μg of Moderna’s mRNA-1273 vaccine, a single immunization of 30 μg, or no vaccine. Two doses of 100 μg of mRNA-1273 induced reciprocal ID 50 mean neutralizing antibody titers against live SARS-CoV-2 D614G and B.1.351 of 3,300 and 240, respectively. Higher neutralizing responses against B.1.617.2 were also observed after two doses compared to a single dose. Following challenge with B.1.351, there was ~4–5−log 10 reduction of viral subgenomic RNA (sgRNA) and low to undetectable replication in bronchoalveolar lavages in the two-dose vaccine groups, with a 1−log 10 reduction in nasal swabs (NS) in the 100 μg dose group. These data establish that a two-dose regimen of mRNA-1273 will be critical for providing upper and lower airway protection against major variants of concern.