Immunogenicity and safety of an Omicron XBB.1.16 adapted vaccine for COVID-19: Interim results from a randomized, controlled, non-inferiority clinical trial

Abstract

Background Global COVID-19 vaccination adapts to protect populations from emerging variants. This communication presents interim findings from the new Omicron XBB adapted PHH-1V81 vaccine compared to a XBB adapted mRNA vaccine against XBB and JN.1 SARS-CoV-2 strains. Methods In a Phase IIb/III pivotal trial, adults previously vaccinated with a primary scheme and at least one booster dose of an EU-approved mRNA vaccine randomly received either PHH-1V81 or BNT162b2 XBB.1.5 vaccine booster as a single dose. The primary efficacy endpoint assessed neutralisation titers against the Omicron XBB.1.16 variant at day 14. Secondary endpoints evaluated neutralization titers and cellular immunity against different variants. Safety endpoints comprised solicited reactions up to day 7 post-vaccination and serious adverse events until the cut-off date of the interim analysis. Changes in humoral responses were reported as GMT and GMFR assessed by PBNA or VNA. Results At the cut-off date, immunogenicity assessments included 599 participants. Both boosters elicited neutralizing antibodies against XBB.1.5, XBB.1.16 and JN.1 with PHH-1V81 inducing a higher response for all variants. PHH-1V8 booster triggers a superior neutralizing antibodies response against XBBs variants compared to the mRNA vaccine. Subgroup analysis consistently revealed higher neutralizing antibody responses with PHH-1V81 across age groups, number of prior vaccination shots, and SARS-CoV-2 infection history. Safety analysis involved 607 participants at the day 14 visit, revealing favourable safety profiles without any serious vaccine-related adverse events at cut-off date of the interim analysis (12th December 2023). Conclusions PHH-1V81 demonstrates superiority on humoral immunogenicity compared to mRNA vaccine agains XBB variants and non-inferiority against JN.1 with favourable safety profile and lower reactogenicity, confirming its potential as vaccine candidate. Trial registration numbers:NCT06181292; EU CT No: 2023-508458-25-00