Immunogenicity and safety of Papilloguard® 4, the first quadrivalent HPV vaccine combined with adjuvant system 04, versus Gardasil® in healthy 15-25-year-old individuals: a phase III, randomized, double-blind, non-inferiority trial.
OBJECTIVE Papilloguard® is developed by Nivad Pharmed Salamat as a quadrivalent human papillomavirus (HPV) vaccine, uniquely combined with the adjuvant system 04 (AS04). The objective of this study was to evaluate the immunogenicity and safety of the quadrivalent Papilloguard® in comparison with Gardasil® (Merck). METHODS This study enrolled 670 healthy participants aged 15-25 years. Vaccines were administered at Months 0, 2, and 6. Immunogenicity was assessed by geometric mean concentrations of HPV-specific antibodies at days 60, 180, and 210. Safety data were collected through direct monitoring, phone follow-ups, and diary cards. RESULTS Papilloguard® demonstrated non-inferior immunogenicity compared to Gardasil® across all four HPV types at day 210. Moreover, Papilloguard® demonstrated consistently higher geometric mean antibody concentrations across all four HPV types compared with Gardasil®. Seroconversion rates were also higher for HPV types 6, 11, and 18 at day 210 in the Papilloguard® group. However, superiority analyses were not prespecified and these findings should be interpreted cautiously. This enhanced immunogenicity may be associated with the AS04 in the quadrivalent formulation. Most reported adverse events were grade 1 or 2. Vaccination site pain was observed in both groups as the most commonly reported local solicited adverse event. Headache and fatigue were the most frequently reported systemic solicited adverse events. Two serious adverse events were reported in each group, none of which were considered related to the vaccines. While associated with increased local reactogenicity, the overall safety profile of Papilloguard® was acceptable and comparable to other HPV vaccines. CONCLUSION Papilloguard®, the first quadrivalent HPV vaccine combined with AS04, demonstrated non-inferior immunogenicity compared to Gardasil® for HPV types 6, 11, 16, and 18. Despite a higher incidence of local reactogenicity, likely associated with AS04, Papilloguard® showed enhanced immunogenicity while maintaining an acceptable overall safety profile, positioning it as a promising HPV vaccine.