Immunogenicity and Safety of PHH-1V COVID-19 Vaccine as a Heterologous Booster in Adolescents

Abstract Objectives Although rare, severe complications may follow SARS-CoV-2 infection in pediatric populations. PHH-1V, a protein-based, bivalent, adjuvanted COVID-19 vaccine, demonstrated strong immunogenicity and favorable safety as a booster in adults. This study further evaluated PHH-1V as a heterologous booster in pediatric adolescent population. Study design HIPRA-HH-3 was a phase IIb, open-label, multicenter, non-inferiority trial assessing the immunogenicity and safety of PHH-1V in 240 healthy adolescents (≥ 12 to < 18 years) previously vaccinated with BNT162b2. Immunogenicity (N = 88) was evaluated by measuring neutralizing antibodies against SARS-CoV-2 variants, total binding antibodies, and T-cell responses at day 14 post-booster, compared to young adults (≥ 18 to ≤ 25 years) (N = 81) from the previous HIPRA-HH-2 study, who had also received the PHH-1V booster vaccine. Safety endpoints included all adverse events through day 28. Results Neutralizing titers against Omicron BA.1 (primary endpoint), WH1, Beta, and Delta variants and total binding antibodies were significantly higher in adolescents than in young adults (p < 0.001), demonstrating non-inferiority (margin < 1.5). T-cell responses against Omicron BA.1 and Beta variants also increased significantly (p < 0.001). Adverse events were mostly mild or moderate, primarily injection-site pain and headache. No serious adverse events were reported. Conclusions PHH-1V is safe and immunogenic as a heterologous booster in adolescents, inducing both humoral and cellular responses with SARS-CoV-2 cross-variant immune recognition. These findings support the use of PHH-1V in adolescent vaccination strategies. Additional data on long-term protection in this population, including specific risk groups, remain needed. Clinical Trial Registration: NCT06234956 and 2023-504639-42-00.