COVID-19 trimeric S-protein subunit vaccine(trivalent)(Clover Biopharmaceuticals AUS)

Data are limited on the protective role of the Omicron BA bivalent vaccine, previous infection, and their induced neutralizing antibodies against Omicron XBB.1.16 and EG.5.1 infection.

We conducted a nested case-control analysis among tertiary hospital staff in Tokyo who had received ≥3 doses of COVID-19 vaccines and donated blood samples in June 2023 (1 month before the Omicron XBB.1.16 and EG.5.1 wave). We identified 206 symptomatic cases between June and September 2023 and selected their controls with 1:1 propensity score matching. We examined the association of vaccination, previous infection, and preinfection live virus neutralizing antibody titers against Omicron XBB.1.16 and EG.5.1 with the risk of COVID-19 infection.

Previous infection during the Omicron BA- or XBB-dominant phase was associated with a significantly lower infection risk during the XBB.1.16 and EG.5.1–dominant phase than infection-naive status, with 70% and 100% protection, respectively, whereas Omicron BA bivalent vaccination showed no association. Preinfection neutralizing titers against XBB.1.16 and EG.5.1 were 39% (95% CI, 8%–60%) and 28% (95% CI, 8%–44%) lower in cases than matched controls. Neutralizing activity against XBB.1.16 and EG.5.1 was somewhat detectable in the sera of individuals with previous infection but barely detectable in those who were infection naive and received the Omicron bivalent vaccine.

In the era when the Omicron XBB vaccine was unavailable, the Omicron BA bivalent vaccine did not confer the neutralizing activity and protection against Omicron XBB.1.16 and EG.5.1 symptomatic infection. The previous infection afforded neutralizing titers and protection against symptomatic infection with these variants.

Monovalent Omicron XBB.1.5 mRNA vaccines were newly developed and approved by the FDA in Autumn 2023 for preventing COVID‐19. However, clinical efficacy for these vaccines is currently lacking. We previously established the quantification of antigen‐specific antibody sequence (QASAS) method to assess the response to severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) vaccination at the mRNA level using B‐cell receptor (BCR) repertoire assay and the coronavirus antibody database (CoV‐AbDab). Here, we used this method to evaluate the immunogenicity of monovalent XBB.1.5 vaccines. We analyzed repeated blood samples of healthy volunteers before and after monovalent XBB.1.5 vaccination (BNT162b2 XBB.1.5 or mRNA‐1273.815) for the BCR repertoire to assess BCR/antibody sequences that matched SARS‐CoV‐2‐specific sequences in the database. The number of matched unique sequences and their total reads quickly increased 1 week after vaccination. Matched sequences included those bound to the Omicron strain and Omicron XBB sublineage. The antibody sequences that can bind to the Omicron strain and XBB sublineage revealed that the monovalent XBB.1.5 vaccines showed a stronger response than previous vaccines or SARS‐CoV‐2 infection before the emergence of XBB sublineage. The QASAS method was able to demonstrate the immunogenic effect of monovalent XBB.1.5 vaccines for the 2023–2024 COVID‐19 vaccination campaign.