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@ARTICLE{Mariz:182177,
author = {F. C. Mariz$^*$ and K. Balz$^*$ and M. Dittrich$^*$ and Y.
Zhang$^*$ and F. Yang$^*$ and X. Zhao$^*$ and A. Bolchi and
S. Ottonello and M. Müller$^*$},
title = {{A} broadly protective vaccine against cutaneous human
papillomaviruses.},
journal = {npj vaccines},
volume = {7},
number = {1},
issn = {2059-0105},
address = {[London]},
publisher = {Nature Publishing Group},
reportid = {DKFZ-2022-02479},
pages = {116},
year = {2022},
note = {#EA:F035#LA:F035#},
abstract = {Skin colonization by human papillomavirus (HPV) is
typically related to inconspicuous cutaneous infections
without major disease or complications in immunocompetent
individuals. However, in immunosuppressed patients,
especially organ transplanted recipients, cutaneous HPV
infections may cause massive, highly spreading and recurrent
skin lesions upon synergism with UV-exposure. Current HPV
prophylactic vaccines are not effective against cutaneous
HPV types (cHPV). By applying a modular polytope-based
approach, in this work, we explored different vaccine
candidates based on selected, tandemly arranged cHPV-L2
epitopes fused to thioredoxin (Trx) as a scaffold protein.
Upon conversion to heptameric nanoparticles with the use of
a genetically fused oligomerization domain, our candidate
Trx-L2 vaccines induce broadly neutralizing immune responses
against 19 cHPV in guinea pigs. Similar findings were
obtained in mice, where protection against virus challenge
was also achieved via passive transfer of immune sera.
Remarkably, immunization with the candidate cHPV vaccines
also induced immune responses against several mucosal low-
and high-risk HPV types, including HPV16 and 18. Based on
cumulative immunogenicity data but also on ease and yield of
production, we identified a lead vaccine candidate bearing
12 different cHPV-L2 epitopes that holds great promise as a
scalable and GMP production-compatible lead molecule for the
prevention of post-transplantation skin lesions caused by
cHPV infection.},
cin = {F035},
ddc = {610},
cid = {I:(DE-He78)F035-20160331},
pnm = {316 - Infektionen, Entzündung und Krebs (POF4-316)},
pid = {G:(DE-HGF)POF4-316},
typ = {PUB:(DE-HGF)16},
pubmed = {pmid:36216845},
pmc = {pmc:PMC9550855},
doi = {10.1038/s41541-022-00539-0},
url = {https://inrepo02.dkfz.de/record/182177},
}