SARS-CoV-2 BA.4 and BA.5 lineages have been the dominant strains in most regions worldwide and are continuously gaining mutations in the receptor-binding domain. Multiple BA.4 and BA.5 subvariants with Arg346 mutations in the spike glycoprotein have been identified in various countries, such as BA.4.6, BF.7, BA.5.2.6, BA.4.1.9, and BE.1.2 harbouring Arg346Thr; BA.4.7 and BF.13 harbouring Arg346Ser; and BA.5.9 with Arg346Ile mutations (appendix p 4). These subvariants, especially BA.4.6, exhibit growth advantages compared with other variants including the original BA.4 and BA.5 strains. Previous studies have identified Arg346 as an important immunogenic residue because Arg346 mutations would allow the virus to escape neutralisation by a large group of neutralising antibodies. Unlike Arg346Lys carried by BA.1.1, which maintained a similar chemical property, mutations from Arg to either Thr, Ser, or Ile correspond to a much stronger shift in antibody recognition.
The efficacy of vaccines and neutralising antibody drugs against these BA.4 and BA.5 sublineages needs immediate evaluation.
In this study, we measured the neutralising titres of plasma samples against the SARS-CoV-2 BA.4 and BA.5 subvariants with Arg346 mutations. The plasma samples were obtained from vaccinated individuals that received three doses of an inactivated vaccine (CoronaVac) without SARS-CoV-2 infection or with BA.1, BA.2, or BA.5 breakthrough infection (appendix pp 7–9). Plasma from breakthrough infections were obtained 3 to 5 weeks after a positive PCR test for SARS-CoV-2. Vesicular stomatitis virus-based pseudoviruses were used in the neutralisation assays.