SARS-CoV-2 Omicron's newest subvariant BQ.1.1 shows extraordinary immune evasion potential against vaccine sera

In a recent study posted to the bioRxiv* preprint server, researchers pursued immunological evidence of why BQ.1.1 prevalence swiftly increased in areas where Omicron BA.5 was dominant in the United States (US).

Background

Studies have shown that Omicron BQ.1.1 cases rapidly increased in frequency in the US, and Omicron BA.5 cases declined to less than half, where not long ago, Omicron BA.5 was the dominant severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) variant. Thus, it is crucial to determine how BQ.1.1 evades neutralizing antibodies (nAbs) induced by coronavirus disease 2019 (COVID-19) vaccination and SARS-CoV-2 infection.

About the study

In the present study, researchers assessed nAb titers in 16 individuals who were vaccinated and boosted with the monovalent mRNA BNT162b2 vaccine in 2021. Next, they evaluated nAb titers in 15 individuals who received the monovalent mRNA boosters in 2022. Additionally, 18 bivalent mRNA booster recipients, most of whom received three vaccine doses, although some had also received two or four COVID-19 vaccine doses.

Study findings

Following the monovalent BNT162b2 boost, median nAb titers to WA1/2020, BA.5, BF.7, BA.2.75.2, and BQ.1.1 were 45, 695, 887, 595, 387, and 261, respectively. The authors noted that the median nAb titers against BQ.1.1 were much diminished than the median nAb titers against WA1/2020 and BA.5 by factors of 175 and 3, respectively.

Compared to the uninfected 2021 cohort, most were likely infected in these cohorts, although the documented rates for SARS-CoV-2 Omicron infections were as low as 33%. Also, WA1/2020 and Omicron nAb titers were higher in the two 2022 cohorts even before boosting. After boosting, their median NAb titers to WA1/2020, BA.5, BF.7, BA.2.75.2, and BQ.1.1 were 40,515, 3693, 2399, 883, and 508, respectively.

Conclusions

The study results showed that compared to BA.5, both BA.2.75.2 and BQ.1.1 escaped nAbs-elicited by prior infection and vaccination more effectively. The effect was most pronounced for BQ.1.1, whose nAb titers were lower than BA.5 by a factor of seven across study cohorts.

These findings present an immunological explanation for the prompt surge in BQ.1.1 prevalence in regions where BA.5 was dominant in the US, which has implications for both vaccine and natural immunity. Also, it puts into perspective how the presence of the R346T mutation in multiple new Omicron subvariants is likely a consequence of convergent evolution.

*Important notice

bioRxiv publishes preliminary scientific reports that are not peer-reviewed and, therefore, should not be regarded as conclusive, guide clinical practice/health-related behavior, or treated as established information.