Next generation L2-based HPV vaccines cross-protect against cutaneous papillomavirus infection and tumor development

• Published in: Frontiers in immunology Vol. 13; p. 1010790
• Main Authors: Ahmels, Melinda, Mariz, Filipe C, Braspenning-Wesch, Ilona, Stephan, Sonja, Huber, Bettina, Schmidt, Gabriele, Cao, Rui, Müller, Martin, Kirnbauer, Reinhard, Rösl, Frank, Hasche, Daniel
• Format: Journal Article
• Language: English
• Published: Switzerland Frontiers Media S.A 03.10.2022
• Subjects: animal model; Animals; Antibodies, Neutralizing; Capsid Proteins; cross-protection; cutaneous HPV; Humans; Immunology; L2-based vaccine; Mice; Mice, Inbred BALB C; Neoplasms; Neutralization Tests; next generation vaccine; Oncogene Proteins, Viral; Papillomaviridae; Papillomavirus Infections; Papillomavirus Vaccines; Peptides; skin tumors; Vaccines, Virus-Like Particle; next generation vaccine; skin tumors; L2-based vaccine; cutaneous HPV; animal model; Mastomys coucha; cross-protection; skin tumor formation
• ISSN: 1664-3224; 1664-3224
• DOI: 10.3389/fimmu.2022.1010790

Licensed L1-VLP-based immunizations against high-risk mucosal human papillomavirus (HPV) types have been a great success in reducing anogenital cancers, although they are limited in their cross-protection against HPV types not covered by the vaccine. Further, their utility in protection against cutaneous HPV types, of which some contribute to non-melanoma skin cancer (NMSC) development, is rather low. Next generation vaccines achieve broadly cross-protective immunity against highly conserved sequences of L2. In this exploratory study, we tested two novel HPV vaccine candidates, HPV16 RG1-VLP and CUT-PANHPVAX, in the preclinical natural infection model . After immunization with either vaccines, a mock control or MnPV L1-VLPs, the animals were experimentally infected and monitored. Besides vaccine-specific seroconversion against HPV L2 peptides, the animals also developed cross-reactive antibodies against the cutaneous papillomavirus (MnPV) L2, which were cross-neutralizing MnPV pseudovirions . Further, both L2-based vaccines also conferred protection as the viral loads in plucked hair after experimental infection were lower compared to mock-vaccinated control animals. Importantly, the formation of neutralizing antibodies, whether directed against L1-VLPs or L2, was able to prevent skin tumor formation and even microscopical signs of MnPV infection in the skin. For the first time, our study shows the proof-of-principle of next generation L2-based vaccines even across different PV genera in an infection animal model with its genuine PV. It provides fundamental insights into the humoral immunity elicited by L2-based vaccines against PV-induced skin tumors, with important implications to the design of next generation HPV vaccines.