Protection against SARS-CoV-2 Beta variant in mRNA-1273 vaccine–boosted nonhuman primates

Abstract

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.

mRNA-based COVID-19 vaccine boosters induce neutralizing immunity against SARS-CoV-2 Omicron variant

“…Interestingly, vaccinated individuals who received an additional “booster” mRNA vaccine dose generated the most potent and cross-reactive antibody responses of any cohort tested, including individuals who recently received their primary series. The effect was similar to that observed following mRNA vaccine boosting in rhesus macaques ( Corbett et al, 2021 ). This substantial difference in Omicron cross-neutralization was surprising, given that two-dose and three-dose vaccine regimens elicited comparable levels of wild-type neutralization and because the immunogen was identical for all doses, which would be expected to elicit memory responses from the existing, strain-specific antibody repertoire.…”

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

“…In contrast to the data with B.1.617.2, live virus neutralizing titers to B.1.351 showed a modest increase from week 24 to 48 (p = 0.0323). This observation, together with a difference in the kinetics of neutralizing titers to B.1.617.2 and B.1.351, suggests a change in serum epitope dominance and/or increased antibody affinity maturation, consistent with data showing a continued evolution of antibody responses induced by mRNA and adenovirus-vectored vaccines in NHPs and humans (Barouch et al, 2021;Corbett et al, 2021a;Gonzalez Lopez Ledesma et al, 2021).…”

“…Recent studies in the United Kingdom, United States, and Qatar have shown a reduced efficacy of mRNA-based vaccines against asymptomatic and symptomatic, but not severe, B.1.617.2 infection (Bruxvoort et al, 2021;Chemaitelly et al, 2021;Lopez Bernal et al, 2021;Puranik et al, 2021;Tang et al, 2021). Antibody titers significantly decrease over a 6-month interval after the initial immunization series (Canaday et al, 2021;Corbett et al, 2021a;Levin et al, 2021), raising the concern that protection may wane. We and others reported that binding and neutralizing antibody titers in nonhuman primates (NHPs) and humans are key correlates of protection for mRNA and adenovirus-vectored COVID-19 vaccines (Corbett et al, 2021b;Gilbert et al, 2021;Khoury et al, 2021;Roozendaal et al, 2021).…”

Molecular probes of spike ectodomain and its subdomains for SARS-CoV-2 variants, Alpha through Omicron

“…Through this strategy, we have produced wildtype SARS-CoV-2 spike ectodomain and subdomain probes allowing for the identification of potent neutralizing antibodies and nanobodies that target the receptor binding domain (RBD) or the N-terminal domain (NTD) of SARS-CoV-2 [14–19], the characterization of antibody binding affinities and specificities, and the quantification of immune responses against spike and its subdomains in nonhuman primates to inform vaccine development [20, 21] and to find correlates of elicited responses with neutralization [22]. Moreover, with the rise of SARS-CoV-2 VOCs, we found that probes incorporating mutations defined by the variants could be helpful in the characterization of the impact of VOC mutations on vaccine effectiveness [23–25].…”