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

BACKGROUND AND OBJECTIVES PHH-1V, a protein-based, non-mRNA, bivalent, adjuvanted COVID-19 vaccine, has demonstrated strong immunogenicity and favorable safety as a booster in adults. This study evaluated PHH-1V as a heterologous booster in adolescents. METHODS HIPRA-HH-3 was a phase IIb, open-label, multicenter, noninferiority trial assessing the immunogenicity and safety of PHH-1V in 240 healthy adolescents (≥ 12 to < 18 years) primed with BNT162b2. Immunogenicity (N = 90) was assessed by measuring neutralizing antibodies against SARS-CoV-2 variants and total binding antibodies in adolescent participants vs young adults (≥ 18 to ≤ 25 years) (N = 81) from a previous trial, who had also been boosted with PHH-1V. T-cell responses at day 14 post booster were also evaluated. Antibody durability and adverse events (AEs) were assessed through day 336. 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 < .001), demonstrating noninferiority (margin < 1.5). T-cell responses against BA.1 and Beta also increased significantly (P < .001). Cross-variant antibody titers remained above baseline (day 0) through day 336. AEs were mostly mild/moderate, primarily injection-site pain and headache within 28 days. No related serious AEs were reported. CONCLUSIONS As a heterologous booster in adolescents, PHH-1V is safe and elicits cellular and sustained humoral responses with cross-variant immune recognition, which support the use of PHH-1V in adolescent vaccination strategies. Data in younger and specific risk groups are still needed.