TY  - JOUR
AU  - Ahmels, Melinda
AU  - Mariz, Filipe C
AU  - Braspenning-Wesch, Ilona
AU  - Stephan, Sonja
AU  - Huber, Bettina
AU  - Schmidt, Gabriele
AU  - Cao, Rui
AU  - Müller, Martin
AU  - Kirnbauer, Reinhard
AU  - Rösl, Frank
AU  - Hasche, Daniel
TI  - Next generation L2-based HPV vaccines cross-protect against cutaneous papillomavirus infection and tumor development.
JO  - Frontiers in immunology
VL  - 13
SN  - 1664-3224
CY  - Lausanne
PB  - Frontiers Media
M1  - DKFZ-2022-02487
SP  - 1010790
PY  - 2022
N1  - #EA:F030#EA:F035#LA:F030#
AB  - 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.
KW  - Mice
KW  - Animals
KW  - Humans
KW  - Papillomavirus Vaccines
KW  - Papillomavirus Infections
KW  - Oncogene Proteins, Viral
KW  - Vaccines, Virus-Like Particle
KW  - Neutralization Tests
KW  - Capsid Proteins
KW  - Mice, Inbred BALB C
KW  - Papillomaviridae
KW  - Antibodies, Neutralizing
KW  - Neoplasms
KW  - Peptides
KW  - L2-based vaccine (Other)
KW  - Mastomys coucha (Other)
KW  - animal model (Other)
KW  - cross-protection (Other)
KW  - cutaneous HPV (Other)
KW  - next generation vaccine (Other)
KW  - skin tumor formation (Other)
KW  - skin tumors (Other)
KW  - Papillomavirus Vaccines (NLM Chemicals)
KW  - Oncogene Proteins, Viral (NLM Chemicals)
KW  - Vaccines, Virus-Like Particle (NLM Chemicals)
KW  - Capsid Proteins (NLM Chemicals)
KW  - Antibodies, Neutralizing (NLM Chemicals)
KW  - Peptides (NLM Chemicals)
LB  - PUB:(DE-HGF)16
C6  - pmid:36263027
C2  - pmc:PMC9574214
DO  - DOI:10.3389/fimmu.2022.1010790
UR  - https://inrepo02.dkfz.de/record/182185
ER  -