A broadly protective vaccine against cutaneous human papillomaviruses

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 massiv...

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Bibliographic Details
Published in:npj vaccines 2022-10, Vol.7 (1), p.116-116, Article 116
Main Authors: Mariz, Filipe Colaco, Balz, Kathrin, Dittrich, Manuela, Zhang, Yueru, Yang, Fan, Zhao, Xueer, Bolchi, Angelo, Ottonello, Simone, Müller, Martin
Format: Article
Language:English
Subjects:
631/250/255/2514
631/250/590/2294
Biomedical and Life Sciences
Biomedicine
Human papillomavirus
Immunity (Disease)
Immunization
Immunogenicity
Infectious Diseases
Lesions
Medical Microbiology
Public Health
Skin diseases
Synergism
Vaccine
Vaccines
Virology
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Summary: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.
ISSN:2059-0105
2059-0105
DOI:10.1038/s41541-022-00539-0