%0 Journal Article
%A Ahmels, Melinda
%A Mariz, Filipe C
%A Braspenning-Wesch, Ilona
%A Stephan, Sonja
%A Huber, Bettina
%A Schmidt, Gabriele
%A Cao, Rui
%A Müller, Martin
%A Kirnbauer, Reinhard
%A Rösl, Frank
%A Hasche, Daniel
%T Next generation L2-based HPV vaccines cross-protect against cutaneous papillomavirus infection and tumor development.
%J Frontiers in immunology
%V 13
%@ 1664-3224
%C Lausanne
%I Frontiers Media
%M DKFZ-2022-02487
%P 1010790
%D 2022
%Z #EA:F030#EA:F035#LA:F030#
%X 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 Mastomys coucha. 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 Mastomys natalensis papillomavirus (MnPV) L2, which were cross-neutralizing MnPV pseudovirions in vitro. Further, both L2-based vaccines also conferred in vivo 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.
%K Mice
%K Animals
%K Humans
%K Papillomavirus Vaccines
%K Papillomavirus Infections
%K Oncogene Proteins, Viral
%K Vaccines, Virus-Like Particle
%K Neutralization Tests
%K Capsid Proteins
%K Mice, Inbred BALB C
%K Papillomaviridae
%K Antibodies, Neutralizing
%K Neoplasms
%K Peptides
%K L2-based vaccine (Other)
%K Mastomys coucha (Other)
%K animal model (Other)
%K cross-protection (Other)
%K cutaneous HPV (Other)
%K next generation vaccine (Other)
%K skin tumor formation (Other)
%K skin tumors (Other)
%K Papillomavirus Vaccines (NLM Chemicals)
%K Oncogene Proteins, Viral (NLM Chemicals)
%K Vaccines, Virus-Like Particle (NLM Chemicals)
%K Capsid Proteins (NLM Chemicals)
%K Antibodies, Neutralizing (NLM Chemicals)
%K Peptides (NLM Chemicals)
%F PUB:(DE-HGF)16
%9 Journal Article
%$ pmid:36263027
%2 pmc:PMC9574214
%R 10.3389/fimmu.2022.1010790
%U https://inrepo02.dkfz.de/record/182185