Immunogenicity and safety of a quadrivalent recombinant human papillomavirus vaccine (type 6/11/16/18) (Hansenula...

The randomized, double-blind, placebo-controlled Phase II non-inferiority clinical study aimed to evaluate the immunogenicity and safety of the quadrivalent recombinant human papillomavirus vaccine (type 6/11/16/18) (Hansenula polymorpha) in healthy females aged 9-45 years.

A total of 1800 participants were randomly assigned to the vaccine group and the placebo group in a 2:1 ratio. The immunobridging between the 9-17 and 18-45 age groups adopts a non-inferiority design with a non-inferiority margin of -10% and a one-sided significance level of 2.5%. Participants received three doses at months 0, 2, and 6. The levels of antibodies against HPV6, 11, 16, and 18 in serum samples before immunization and 30 days after the 3rd dose of vaccination were assessed using a pseudovirus-based neutralization assay (PBNA). Adverse reactions within 30 days after each dose, as well as pregnancies and serious adverse events during the study period, were recorded. (CTR20171447).

Vaccination induced robust neutralizing antibody responses against four HPV types in both seronegative and seropositive participants. In the seronegative group, the seroconversion rates for HPV types 6, 11, 16, and 18 at 30 days after the third dose were 100%, 99.82%, 100%, and 99.73%, respectively. In the baseline seropositive group, more than 91% of participants achieved a ≥4-fold increase in neutralizing antibody titers for all four HPV types. The seroconversion rates in the 9-17-year-old cohort were non-inferior to those in the 18-45-year-old cohort. The three-dose regimen was well-tolerated, with no vaccine-related serious adverse events reported.

The quadrivalent HPV vaccine produced in Hansenula polymorpha demonstrated favorable immunogenicity with seroconversion rates >99% for all four HPV types in seronegative participants and safety in females aged 9 to 45 years, supporting further development for HPV prevention.