Inactivated SARS-CoV-2 Variant B.1.351(South_Africa/KRISP-K005325/2020)

Since its initial emergence, SARS-CoV-2 has evolved significantly, including the emergence of a variant harboring the D614G mutation that has become dominant. However, viruses harboring this mutation alone do not appear to differ significantly in antigenicity. SARS-CoV-2 B.1.1.7 (also known as 501Y.V1 within the GR clade) was first detected in southeast England in September 2020 and quickly became the dominant variant in the UK, likely due to its enhanced transmissibility. This strain has now spread to over 50 countries, and there are signs that it may be more virulent. In addition to the mutation causing the D614G substitution, the spike gene of B.1.1.7 contains eight mutations, including two deletions (ΔH69/ΔV70 and ΔY144) in the N-terminal domain (NTD), a substitution (N501Y) in the receptor binding domain (RBD), and a substitution (P681H) near the furin cleavage site.

SARS-CoV-2 B.1.351 (also known as 501Y.V2 in the GH clade) was first detected in the Eastern Cape province of South Africa in late 2020. Since then, the variant has become the predominant virus species there, raising the possibility of increased transmissibility. In addition to the mutation that causes the D614G substitution, the spike gene of B.1.351 contains nine mutations, including a cluster of mutations in the nerve segment (NTD) (e.g., mutations causing Δ242–Δ244 and R246I), three substitutions in the receptor binding domain (RBD) (K417N, E484K, and N501Y), and one substitution near the furin cleavage site (A701V). The B.1.351 variant neutralizes not only most monoclonal antibodies targeting the N-terminal domain but also multiple monoclonal antibodies targeting the receptor-binding motif of the receptor-binding domain, primarily due to a mutation resulting in the E484K substitution. Furthermore, B.1.351 exhibited significantly stronger neutralizing potency against convalescent plasma (9.4-fold) and sera from vaccinated individuals (10.3-12.4-fold) than wild-type SARS-CoV-2.