Humoral Immune Response Against XBB.1.5 and BQ.1.1 SARS-COV-2 Variants of a Fourth Dose of PHH-1V Vaccine in Adult Subject: Preliminary Results of HIPRA-HH-2 Extension Study

Background: In 2023, COVID-19 cases were mainly associated with BQ.1 and XBB.1.5 subvariants, causing mostly mild cases and boosting hybrid immunity throughout the population. PHH-1V (HIPRA COVID-19 vaccine) is a bivalent recombinant protein vaccine based on the receptor binding domain of Beta and Alpha SARS-CoV-2 variants, which is authorised for commercialisation in the EU (March 30th, 2023) and UK (July 31st, 2023) as a booster for active immunisation to prevent COVID-19 in individuals 16 years of age who have previously received a mRNA vaccine.Methods: The HIPRA-HH-2 extension clinical trial (NCT05142553) started in September 2022 to evaluate the response to a fourth dose of PHH-1V in 288 participants who had either 2 doses of BNT162b2 and 1 dose of PHH-1V (n=106) or 3 doses of BNT162b2 (n=182). The immunogenicity of PHH-1V against different SARS-CoV-2 variants, including Omicron XBB.1.5 and BQ.1.1, was evaluated by pseudovirion-based neutralization assay 14 days after injection. Reported cases of COVID-19 up to May 30, 2023 (coinciding with the period of maximum prevalence of the BQ.1.1 and XBB.1.5 subvariants) were also recorded.Results: A fourth dose of PHH-1V elicited a significant neutralising antibody response against XBB.1.5 (GMT= 284.32, GMFR=5.45) and BQ.1.1 (GMT= 223.48, GMFR= 4.01) 14 days after the booster. Compared to the response triggered by PHH-1V vaccination against previous variants1, the XBB.1.5 and BQ.1.1 neutralising antibody titres were lower, which is similar to the results of other vaccine boosters2,3,4, and after natural infection (n=22, GMT=500.11). On the cut-off date, 34 (11.8%) individuals reported COVID-19, and there were no cases of severe disease, hospitalizations or death due to COVID-19.Conclusions: PHH-1V vaccine elicits a milder response against XBB.1.5 and BQ.1.1 compared to previous variants, although considering the low percentage of individuals reporting infection, the response appears to be sufficient for protection from severe disease.