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@ARTICLE{Ahmels:182185,
      author       = {M. Ahmels$^*$ and F. C. Mariz$^*$ and I.
                      Braspenning-Wesch$^*$ and S. Stephan$^*$ and B. Huber and G.
                      Schmidt$^*$ and R. Cao$^*$ and M. Müller$^*$ and R.
                      Kirnbauer and F. Rösl$^*$ and D. Hasche$^*$},
      title        = {{N}ext generation {L}2-based {HPV} vaccines cross-protect
                      against cutaneous papillomavirus infection and tumor
                      development.},
      journal      = {Frontiers in immunology},
      volume       = {13},
      issn         = {1664-3224},
      address      = {Lausanne},
      publisher    = {Frontiers Media},
      reportid     = {DKFZ-2022-02487},
      pages        = {1010790},
      year         = {2022},
      note         = {#EA:F030#EA:F035#LA:F030#},
      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.},
      keywords     = {Mice / Animals / Humans / Papillomavirus Vaccines /
                      Papillomavirus Infections / Oncogene Proteins, Viral /
                      Vaccines, Virus-Like Particle / Neutralization Tests /
                      Capsid Proteins / Mice, Inbred BALB C / Papillomaviridae /
                      Antibodies, Neutralizing / Neoplasms / Peptides / L2-based
                      vaccine (Other) / Mastomys coucha (Other) / animal model
                      (Other) / cross-protection (Other) / cutaneous HPV (Other) /
                      next generation vaccine (Other) / skin tumor formation
                      (Other) / skin tumors (Other) / Papillomavirus Vaccines (NLM
                      Chemicals) / Oncogene Proteins, Viral (NLM Chemicals) /
                      Vaccines, Virus-Like Particle (NLM Chemicals) / Capsid
                      Proteins (NLM Chemicals) / Antibodies, Neutralizing (NLM
                      Chemicals) / Peptides (NLM Chemicals)},
      cin          = {F030 / F035 / W210},
      ddc          = {610},
      cid          = {I:(DE-He78)F030-20160331 / I:(DE-He78)F035-20160331 /
                      I:(DE-He78)W210-20160331},
      pnm          = {316 - Infektionen, Entzündung und Krebs (POF4-316)},
      pid          = {G:(DE-HGF)POF4-316},
      typ          = {PUB:(DE-HGF)16},
      pubmed       = {pmid:36263027},
      pmc          = {pmc:PMC9574214},
      doi          = {10.3389/fimmu.2022.1010790},
      url          = {https://inrepo02.dkfz.de/record/182185},
}