A second wave of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections in India is leading to the emergence of SARS-CoV-2 variants. The B.1.617.1 (or kappa) and B.1.617.2 (or delta) variants were first identified in India and have rapidly spread to several countries throughout the world. These variants contain mutations within the spike protein located in antigenic sites recognized by antibodies with potent neutralizing activity.^1-3 We used serum samples obtained from infected and vaccinated persons to assess neutralizing activity against the SARS-CoV-2 variants in a live-virus assay.

Antibodies dovetail with protection: Immune correlates of protection are clinical end points used to gauge vaccine-induced immunogenicity and protection. Corbett et al . studied nonhuman primate (NHP) immune responses to various doses of the mRNA-1273 (Moderna) vaccine to provide a range of immune responses and protective outcomes. They determined that circulating spike protein–specific antibodies correlated with protection against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) replication in the airways. Passively transferred NHP antibodies were sufficient to mediate protection against SARS-CoV-2 challenge in hamsters, emphasizing that antibodies are mechanistic correlates. Protection of the lower respiratory tract required lower serum antibody concentrations, possibly explaining why most current vaccines are highly effective against severe lower airway disease. The higher antibody threshold required for reducing upper airway infection has potential implications for boosting to limit transmission. —STS

A look at variant-specific boosters: The evolution of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants of concern (VOCs) has raised the question of whether current COVID-19 vaccines protect against VOCs and if a variant specific vaccine may be needed. Of the currently identified VOCs, the Delta variant is believed to be the most transmissible, whereas the Beta variant appears to be the most vaccine resistant. Corbett et al . looked at the effect of vaccine boosting using either the original WA-1 strain vaccine or a Beta variant–specific booster. Around 6 months after the primary two-dose vaccine series, a third boost vaccination resulted in higher neutralizing antibody levels against VOCs in nonhuman primates. Regardless of whether the boost was from the original vaccine or the Beta-specific version, similar increases in neutralizing antibody levels were observed and resulted in enhanced viral protection. —PNK

Coronavirus vaccines that are highly effective against current and anticipated SARS-CoV-2 variants are needed to control COVID-19. We previously reported a receptor-binding domain (RBD)-sortase A-conjugated ferritin nanoparticle (scNP) vaccine that induced neutralizing antibodies against SARS-CoV-2 and pre-emergent sarbecoviruses and protected non-human primates (NHPs) from SARS-CoV-2 WA-1 infection. Here, we find the RBD-scNP induced neutralizing antibodies in NHPs against pseudoviruses of SARS-CoV and SARS-CoV-2 variants including 614G, Beta, Delta, Omicron BA.1, BA.2, BA.2.12.1, and BA.4/BA.5, and a designed variant with escape mutations, PMS20. Adjuvant studies demonstrate variant neutralization titers are highest with 3M-052-aqueous formulation (AF). Immunization twice with RBD-scNPs protect NHPs from SARS-CoV-2 WA-1, Beta, and Delta variant challenge, and protect mice from challenges of SARS-CoV-2 Beta variant and two other heterologous sarbecoviruses. These results demonstrate the ability of RBD-scNPs to induce broad neutralization of SARS-CoV-2 variants and to protect animals from multiple different SARS-related viruses. Such a vaccine could provide broad immunity to SARS-CoV-2 variants.