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| Home > Publications database > Next generation L2-based HPV vaccines cross-protect against cutaneous papillomavirus infection and tumor development. |
| Home > Publications database > Next generation L2-based HPV vaccines cross-protect against cutaneous papillomavirus infection and tumor development. |
| Journal Article | DKFZ-2022-02487 |
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2022
Frontiers Media
Lausanne
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Please use a persistent id in citations: doi:10.3389/fimmu.2022.1010790
Abstract: 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.
Keyword(s): Mice (MeSH) ; Animals (MeSH) ; Humans (MeSH) ; Papillomavirus Vaccines (MeSH) ; Papillomavirus Infections (MeSH) ; Oncogene Proteins, Viral (MeSH) ; Vaccines, Virus-Like Particle (MeSH) ; Neutralization Tests (MeSH) ; Capsid Proteins (MeSH) ; Mice, Inbred BALB C (MeSH) ; Papillomaviridae (MeSH) ; Antibodies, Neutralizing (MeSH) ; Neoplasms (MeSH) ; Peptides (MeSH) ; L2-based vaccine ; Mastomys coucha ; animal model ; cross-protection ; cutaneous HPV ; next generation vaccine ; skin tumor formation ; skin tumors ; Papillomavirus Vaccines ; Oncogene Proteins, Viral ; Vaccines, Virus-Like Particle ; Capsid Proteins ; Antibodies, Neutralizing ; Peptides
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