The COVID-19 pandemic remains a significant global concern owing to the emergence of the Omicron variants and its descendant subvariants.1,2,3 Evidence suggests that the increasing prevalence and rapidly expanding spike (‘S’) mutations of the currently circulating subvariants BQ.1, and BQ.1.1 (evolved from Omicron BA.5) and XBB and XBB.1 (recombinants of Omicron BA.2, BJ.1 and BA.2.75 sub-lineages) are potential threats to the efficacy of current COVID-19 vaccines and monoclonal antibody (mAb) therapies.
Most recently, Wang Q and colleagues4 conducted a study to evaluate the neutralization potential of XBB, XBB.1, BQ.1, and BQ.1.1, using sera from five different clinical cohorts. The first two cohorts were composed of individuals who received either three or four doses of an original COVID-19 mRNA vaccine, referred to as ‘3 shots wild type [WT]’ or ‘4 shots WT’, respectively.4 The third cohort included recipients of three doses of an original COVID-19 mRNA vaccine plus a fourth booster dose of a recently authorized bivalent mRNA vaccine (‘3 shots WT + bivalent’).4 The remaining two cohorts comprised of patients who suffered BA.2 and BA.4 or BA.5 breakthrough infections post-vaccination (referred to as ‘BA.2 breakthrough’ and ‘BA.4/5 breakthrough’, respectively).4
The populated serum neutralization data was used to build an antigenic map that exhibited the antigenic distances among D614G (ancestral strain), the wildtype SARS-CoV-2 variant, and the Omicron subvariants.4 Additionally, the research team constructed pseudoviruses corresponding to each subvariant and individual mutations found in the subvariants. This step enabled researchers to understand the types of serum antibodies that lost neutralizing activity against BQ.1, BQ.1.1, XBB and XBB.1.4 The results were further analyzed against a panel of 23 mAbs targeting SARS-CoV-2 ‘S’ epitopes, to elucidate the preventative or therapeutic effectiveness of mAbs against newer subvariants. The panel comprised of mAbs that previously exhibited substantial neutralizing activity against Omicron, namely bebtelovimab and tixagevimab + cilgavimab (a therapeutic combination of COV2-2196 and COV2-2130 mAbs).4
Key findings of the study included:4
The outcomes of the aforementioned study indicated that both COVID-19 mRNA vaccines (irrespective of the patient’s history of prior SARS-CoV-2 infections) and booster doses of novel bivalent (WA1-BA.5) mRNA vaccines were unable to confer protection against any of the studied Omicron XB and BQ subvariants.4 Furthermore, the extensive antigenic drift exhibited by the Omicron subvariants have raised significant concerns in the context of their antibody evasion properties.4
Thereby, the authors emphasized that the newly emerged Omicron BQ and XB subvariants may compromise the efficacy of COVID-19 vaccines that are currently available, with the potential to cause a surge in SARS-CoV-2 breakthrough and re-infections.4 Additionally, the resistance of BQ and XBB sub-lineages against bebtelovimab may pose a potential threat to COVID-19 therapeutic care, particularly when treating immunocompromised patients. Overall, the findings outlined the importance of ongoing development of vaccines and mAb therapies that can better combat the evolving antigenic trajectory of SARS-CoV-2.4