HPV-VLPs as a Multivalent Nanoparticle Vaccine Platform
Human papillomavirus (HPV) virus-like particles (VLPs) are commonly used as antigens in licensed vaccines, such as Gardasil® 9 (Merck & Co.) and Cervarix® (GlaxoSmithKline), providing protection from persistent HPV infections and cervical cancer. These highly immunogenic VLPs consist of the HPV L1 major capsid protein, which forms pentamers upon expression, facilitating self-assembly into small icosahedral nanoparticles measuring 50 - 60 nm in diameter.
Recently, we investigated the potential of these particles as an antigen carrier platform. Covalently coupling HIV Envelope (Env) to the VLP surface significantly improved the Env-specific antibody response in vivo compared to unconjugated Env (Wang et al., Sci Rep, 2025). Concordantly, Tu et al. demonstrated that conjugating peptides to the VLP surface could also improve the immune response against them, showcasing the potential of HPV VLPs as a nanoparticle carrier platform to enhance the immune response against low immunogenic targets (Tu et al., J Ovarian Res, 2024).
Due to the recommendation to vaccinate young boys and girls against high-risk HPV serotypes, significant portions of the population in Germany possess a pre-existing HPV-specific immune response. This includes not only HPV-specific affinity-matured antibodies, but also an increased number of L1-specific T helper cells. Our aim is to utilize these L1-specific T helper cells to enhance the vaccine-induced immune response against other low immunogenic antigens, such as Env. HPV-VLPs displaying Env could potentially be recognized by Env-specific B cells. These would subsequently present not only Env peptides on their major histocompatibility complexes, but also MHC-II-restricted HPV peptides, allowing for T-cell help for Env-specific B cells by pre-existing HPV-specific T helper cells.
To achieve this, we aim to optimize the covalent coupling of Env to the nanoparticles to completely cover the surface of the HPV-VLPs with Env, thereby shielding the conjugates against HPV-specific antibodies. Otherwise, anamnestic HPV-VLP antibody responses may compete with the induction HIV Env antibody responses.
