Plaque-neutralizing antibody to BA.2.12.1, BA.4 and BA.5 in individuals with three doses of BioNTech or CoronaVac vaccines, natural infection and breakthrough infection

•Omicron BA.5 subvariant is now the predominant COVID-19 threat worldwide. While there are some data on pseudovirus neutralization titres to BA.4/5 in comparison to ancestral virus and BA.1 and BA.2 variants, live virus plaque neutralization is the definitive method to address this important question.•BA.4 and BA.5 subvariants were less susceptible to BNT162b2 or Coronavac vaccine elicited antibody neutralization than subvariants BA.1, BA.2 and BA.2.12.1. Nevertheless, three doses BNT162b2 or booster of BNT162b2 following two doses of CoronaVac elicited detectable BA.4 and BA.5 neutralizing antibody responses while those vaccinated with three doses of CoronaVac largely fail to do so.•Using live virus neutralization, we see some difference between BA.4 and BA.5 subvariants, with BA.5 being even more immune evasive than BA.4, which may help explain why BA.5 outcompeting BA.4 on the global scale.•We provide data on convalescent BA.5, BA.4 and BA.2.12.1 neutralizing titres in convalescent sera of BA.2 breakthrough infections, which reflects the immune landscape for most of the developed world at the moment, as we face the BA.5 outbreak.•BA.2 breakthrough infections in vaccinated individuals elicited higher levels of BA.4 or BA.5 neutralizing antibody compared to BA.2 infections in vaccine-naïve individuals. BA.2.12.1, BA.4 and BA.5 subvariants of SARS-CoV-2 variant-of-concern (VOC) Omicron (B.1.1.529) are spreading globally. They demonstrate higher transmissibility and immune escape. Determine BA.2.12.1, BA.4 and BA.5 virus plaque reduction neutralization test (PRNT) antibody titres in individuals recently vaccinated with BNT162b2 (n=20) or CoronaVac (n=20) vaccines or those convalescent from ancestral wild- type (WT) SARS-CoV-2 (n=20) or BA.2 infections with (n=17) or without (n=7) prior vaccination. Relative to neutralization of the WT virus, those vaccinated with BNT162b2 had 4.8, 3.4, 4.6, 11.3 and 15.5-fold reductions of geometric mean antibody titres (GMT) to BA.1, BA.2, BA.2.12.1, BA.4 and BA.5 viruses, respectively. Similarly, those vaccinated with CoronaVac had 8.0, 7.0, 11.8, 12.0 and 12.0 fold GMT reductions and those with two doses of CoronaVac boosted by BNT162b2 had 6.1, 6.7, 6,3, 13.0 and 21.2 fold GMT reductions to these viruses, respectively. Vaccinated individuals with BA.2 breakthrough infections had higher GMT antibody levels vs. BA.4 (36.9) and BA.5 (36.9) than unvaccinated individuals with BA.2 infections (BA.4 GMT 8.2; BA.5 GMT 11.0). BA