title: Development of AAVLP(HPV16/31L2) particles as broadly protective HPV vaccine candidate.
abstract: The human papillomavirus (HPV) minor capsid protein L2 is a promising candidate for a broadly protective HPV vaccine yet the titers obtained in most experimental systems are rather low. Here we examine the potential of empty AAV2 particles (AAVLPs), assembled from VP3 alone, for display of L2 epitopes to enhance their immunogenicity. Insertion of a neutralizing epitope (amino acids 17-36) from L2 of HPV16 and HPV31 into VP3 at positions 587 and 453, respectively, permitted assembly into empty AAV particles (AAVLP(HPV16/31L2)). Intramuscularly vaccination of mice and rabbits with AAVLP(HPV16/31L2)s in montanide adjuvant, induced high titers of HPV16 L2 antibodies as measured by ELISA. Sera obtained from animals vaccinated with the AAVLP(HPV16/31L2)s neutralized infections with several HPV types in a pseudovirion infection assay. Lyophilized AAVLP(HPV16/31L2) particles retained their immunogenicity upon reconstitution. Interestingly, vaccination of animals that were pre-immunized with AAV2--simulating the high prevalence of AAV2 antibodies in the population--even increased cross neutralization against HPV31, 45 and 58 types. Finally, passive transfer of rabbit antisera directed against AAVLP(HPV16/31L2)s protected naïve mice from vaginal challenge with HPV16 pseudovirions. In conclusion, AAVLP(HPV16/31L2) particles have the potential as a broadly protective vaccine candidate regardless of prior exposure to AAV.
authors: Research Program Infection and Cancer, German Cancer Research Center, Heidelberg, Germany. k.nieto@dkfz.de
authors: Karen
authors: K
authors: Nieto
authors: Margit
authors: M
authors: Weghofer
authors: Peter
authors: P
authors: Sehr
authors: Mirko
authors: M
authors: Ritter
authors: Sebastian
authors: S
authors: Sedlmeier
authors: Balasubramanyam
authors: B
authors: Karanam
authors: Hanna
authors: H
authors: Seitz
authors: Martin
authors: M
authors: Müller
authors: Markus
authors: M
authors: Kellner
authors: Markus
authors: M
authors: Hörer
authors: Uwe
authors: U
authors: Michaelis
authors: Richard B S
authors: RB
authors: Roden
authors: Lutz
authors: L
authors: Gissmann
authors: Jürgen A
authors: JA
authors: Kleinschmidt
mesh_terms: D000276:Adjuvants, Immunologic / Q000008:administration & dosage; D000818:Animals; D004797:Enzyme-Linked Immunosorbent Assay; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D027383:Papillomaviridae / Q000276:immunology*; D011817:Rabbits; D014765:Viral Vaccines / Q000008:administration & dosage / Q000276:immunology*; D014771:Virion
chemical_list: D000276:Adjuvants, Immunologic; D014765:Viral Vaccines