title: Virus-like particles and capsomeres are potent vaccines against cutaneous alpha HPVs.
abstract: The potential as prophylactic vaccines of L1-based particles from cutaneous genus alpha human papillomavirus (HPV) types has not been assessed so far. However, there is a high medical need for such vaccines since HPV-induced skin warts represent a major burden for children and for immunocompromised adults, such as organ transplant recipients. In this study, we have examined the immunogenicity of capsomeres and virus-like particles (VLPs) from HPV types 2, 27, and 57, the most frequent causative agents of skin warts. Immunization of mice induced immune responses resembling those observed upon vaccination with HPV 16 L1-based antigens. The antibody responses were cross-reactive but type-restricted in their neutralizing capacities. Application of adjuvant led to an enhanced potential to neutralize the respective immunogen type but did not improve cross-neutralization. Vaccination with capsomeres and VLPs from all four analyzed HPV types induced robust IFNgamma-associated T-cell activation. Immunization with mixed VLPs from HPV types 2, 27, and 57 triggered an antibody response similar to that after single-type immunization and capable of efficiently neutralizing all three types. Our results imply that vaccination with combinations of VLPs from cutaneous HPV types constitutes a promising strategy to prevent HPV-induced skin lesions.
authors.affiliation: Department of Genome Modifications and Carcinogenesis, German Cancer Research Center, D-69120 Heidelberg, Germany. t.senger@dkfz-heidelberg.de
authors.forename: Tilo
authors.initials: T
authors.lastname: Senger
authors.forename: Lysann
authors.initials: L
authors.lastname: Schädlich
authors.forename: Sonja
authors.initials: S
authors.lastname: Textor
authors.forename: Corinna
authors.initials: C
authors.lastname: Klein
authors.forename: Kristina M
authors.initials: KM
authors.lastname: Michael
authors.forename: Christopher B
authors.initials: CB
authors.lastname: Buck
authors.forename: Lutz
authors.initials: L
authors.lastname: Gissmann
mesh_terms: D000276:Adjuvants, Immunologic / Q000008:administration & dosage; D052685:Alphapapillomavirus / Q000276:immunology*; D000818:Animals; D057134:Antibodies, Neutralizing / Q000097:blood; D000914:Antibodies, Viral / Q000097:blood; D002213:Capsid / Q000276:immunology*; D036022:Capsid Proteins / Q000276:immunology*; D003429:Cross Reactions; D007371:Interferon-gamma / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D009856:Oncogene Proteins, Viral / Q000276:immunology*; D053918:Papillomavirus Vaccines / Q000276:immunology*; D017193:Skin Diseases, Viral / Q000276:immunology / Q000517:prevention & control*; D013601:T-Lymphocytes / Q000276:immunology; D022721:Vaccines, Virosome; D022701:Virosomes / Q000276:immunology*; D014860:Warts / Q000276:immunology / Q000517:prevention & control*
chemical_list: D000276:Adjuvants, Immunologic; D057134:Antibodies, Neutralizing; D000914:Antibodies, Viral; D036022:Capsid Proteins; C114580:HPV L1 protein, Human papillomavirus; D009856:Oncogene Proteins, Viral; D053918:Papillomavirus Vaccines; D022721:Vaccines, Virosome; D022701:Virosomes; D007371:Interferon-gamma