In a recent study published in bioRxiv*, researchers reported that the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Omicron XBB.1.5 variant evades the neutralizing response elicited by bivalent vaccine boosters.
Study: Decreased immunity to XBB.1.5 after bivalent mRNA boosts. Image credit: Fit Zstudio/Shutterstock
background
SARS-CoV-2 Omicron XBB is a hybrid lineage derived from two BA.2 substrains. Subline XBB.1 carries a G252V substitution, while XBB.1.5 carries G252V and F486P substitutions. The frequency of the XBB.1.5 variant increased rapidly, making it the predominant variant in New England. Bivalent messenger ribonucleic acid (mRNA) vaccine boosters amplify the neutralizing antibody (nAb) response to several variants, but less is known about their durability.
The study and conclusions
The present study evaluated immune responses in individuals boosted with bivalent mRNA vaccines. Thirty people who received the bivalent mRNA vaccine boosters from Pfizer or Moderna were included. Subjects were excluded if they had a previous SARS-CoV-2 infection, were positive for anti-nucleocapsid antibodies, or were receiving immunosuppressants.
A pseudovirus neutralization assay was used to determine nAb titers against SARS-CoV-2 variants, including strain WA1 and variants BQ.1.1, BA.2, XBB.1, BA.5, and XBB.1.5 . Intracellular cytokine staining was used to estimate pool 4-positive (CD4+) and CD8+ T cell differentiation responses. Assays were performed at baseline (pre-boost), three weeks and three months after the administration of the booster.
Mean nAb titers at baseline were 5015, 104, 49, and 74 against strain WA1, BA.5, XBB.1, and XBB.1.5, respectively, in SARS-CoV-2 nucleocapsid-seronegative individuals. These titles increased to 25,954 (WA1), 2285 (BA.5), 128 (XBB.1) and 137 (XBB.1.5) in week 3 after the boost. Mean titers of WA1, BA.5, XBB.1, and XBB.1.5 decreased by 1.2-, 1.8-, 2.1-, and 1.8-fold, respectively, relative to week 3 titers.
Median CD8+ T cell responses to WA1 and XBB.1.5 were 0.08% and 0.059% before the boost and 0.107% and 0.106% after three months, respectively. Similarly, median CD4+ T cell responses against WA1 and XBB.1.5 at baseline were 0.098% and 0.065% and 0.099% and 0.09% at month 3 post-boost , respectively.
Conclusions
Findings indicate that SARS-CoV-2 Omicron XBB.1.5 variant significantly evades nAb but not T-cell responses after bivalent mRNA boost vaccination. nAb titers against XBB.1 and XBB.1.5 were comparable, suggesting that the additional F486P substitution in the XBB.1.5 spike enhances transmissibility but not immune evasion.
Notably, nAb titers against the XBB sublines returned to baseline (pre-boost) levels three months after booster administration. This decrease in nAb titers was less pronounced for other variants. The low magnitude of the nAb response and the rapid decline will likely contribute to reduced efficacy of bivalent vaccination; however, preprimed T-cell responses can still protect against severe COVID-19.
*Important news
bioRxiv publishes preliminary scientific reports that are not peer-reviewed and therefore should not be considered conclusive, guide clinical practice/health-related behavior, or be treated as established information.