In a new University of Texas Medical Branch study, the updated bivalent (two-strain) mRNA COVID-19 booster marshaled a robust antibody response against the Omicron BA.4/BA.5 subvariants but not against the more recently emerged BA.2.75.2, BQ.1.1, or XBB.1 strains.
The authors of the study, published yesterday in Nature Medicine, noted that the BA.2.75.2, BQ.1.1, and XBB.1 subvariants have additional mutations in the spike protein that may affect vaccine effectiveness.
The researchers analyzed the neutralizing effects of three human serum panels collected from COVID-naïve participants (25 sera) 23 to 94 days after a fourth dose of the original Moderna or Pfizer/BioNTech COVID-19 vaccine, 14 to 32 days after receipt of an updated booster after two to four doses of the original vaccine (29 sera), or 15 to 32 days after an updated booster from previously infected participants (23 sera) who had received two to four doses of the original formulation.
The updated booster triggered a high level of neutralizing antibodies against BA.4/BA.5 14 to 32 days later, but it didn't generate robust neutralization against BA.2.75.2, BQ.1.1, or XBB.1.
mRNA platform supports rapid adaption
The researchers said that as of Nov 19, 2022, BA.2.75.2 and the BA.4/BA.5-derived sublineages BA.4.6, BF.7, BQ.1, and BQ.1.1 accounted for 0.8%, 4.4%, 7.8%, 25.5%, and 24.2% of US COVID-19 infections, respectively. The BA.5-derived substrain XBB.1, first identified in India in August 2022, is spreading quickly in Europe and has been found in the United States.
"BA.2.75.2, BQ.1.1, and XBB.1 exhibit the greatest evasion against vaccine-elicited neutralization, suggesting the potential of these new sublineages to dethrone BA.5 as the dominant lineage in circulation," they wrote. "Individuals with SARS-CoV-2 infection history develop higher and broader neutralization against the current circulating Omicron sublineages after the BA.5-bivalent booster."
The authors said that the findings show that future boosters should match newly emerged variants. "Given the advantage of mRNA vaccine platform that can rapidly adapt to new antigen sequences, the key challenge is to determine the future booster sequence before new variants become prevalent in circulation," they concluded.