Evaluation of the safety and immunogenicity of a 9-valent human papillomavirus vaccine produced in Saccharomyces cerevisiae using a heating-chilling process for virus-like particle antigen assembly: a double-blind, randomized, placebo-controlled phase 1 clinical trial

Abstract

Background It is challenging to secure the tertiary structure of virus-like particles (VLPs) during manufacturing process development. In this study, we evaluated the safety and immunogenicity of PV-001, a 9-valent human papillomavirus (HPV) vaccine candidate manufactured in Saccharomyces cerevisiae using a new heating-chilling process designed to yield L1 VLPs with high purity and homogeneity. Methods The 9-valent vaccine formulation contained L1 VLPs for HPV types 6, 11, 16, 18, 31, 33, 45, 52, and 58. A double-blind, randomized clinical trial was conducted in which participants were assigned in a 1:1 ratio to receive either the investigation vaccine or a placebo consisting solely of aluminum phosphate (AP) gel, used as an adjuvant. A total of 41 healthy women aged 19-45 years were enrolled in South Korea and administered the assigned intervention via intramuscular injection at 0, 2, and 6 months. Safety assessments included immediate adverse events (AEs), solicited local and systemic AEs, and unsolicited AEs. Immunogenicity was evaluated by measuring serum anti-HPV L1 VLP IgG and neutralizing antibody titers pre-and post-vaccination (ClinicalTrials. gov: NCT07081334). Findings No serious adverse events (AEs) were reported following administration of PV-001, and the overall safety profile was consistent with expected findings, supporting the favorable clinical safety of PV-001. Robust increases in both anti-HPV L1 VLP IgG and neutralizing antibody titers were observed for all nine HPV types following the second and third vaccine doses, relative to baseline. Interpretation PV-001 was well tolerated and elicited strong immunogenic responses, supporting its potential for further clinical development and the evaluation of broader target populations and age groups. Funding This research was supported by a grant of the Korea Health Technology R&D Project through the Korea Health Industry Development Institute (KHIDI), funded by the Ministry of Health & Welfare, Republic of Korea (grant number: RS-2023-KH134909). Copyright (c) 2025 The Author(s). Published by Elsevier Ltd. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).