title: Influence of oxidation and multimerization on the immunogenicity of a thioredoxin-l2 prophylactic papillomavirus vaccine.
abstract: Current commercial prophylactic human papillomavirus (HPV) vaccines are based on virus-like particles assembled from the major capsid protein L1 and show excellent safety and efficacy profiles. Still, a major limitation is their rather narrow range of protection against different HPV types. In contrast, the minor capsid protein L2 contains a so-called major cross-neutralizing epitope that can induce broad-range protective responses against multiple HPV types. This epitope is conserved among different papillomaviruses (PV) and contains two cysteine residues that are present in the L2 proteins of all known PV types. The main challenge in developing L2-directed vaccines is to overcome the intrinsically low immunogenicity of the L2 protein. Previously, we developed a recombinant L2-based prototype vaccine by inserting peptide epitopes spanning the cross-neutralizing L2 sequence into a bacterial thioredoxin (Trx) scaffold. These antigens induced high-titer neutralizing antibodies in mice. Here, we address the question of whether Trx scaffold multimerization may further enhance the immunogenicity of the TrxL2 vaccine. We also demonstrate that the oxidation state of the conserved cysteine residues is not essential for vaccine functionality, but it contributes to immunogenicity.
authors.affiliation: Tumor Virus-Specific Vaccination Strategies, German Cancer Research Center, Heidelberg, Germany.
authors.forename: Hanna
authors.initials: H
authors.lastname: Seitz
authors.forename: Tatiana
authors.initials: T
authors.lastname: Dantheny
authors.forename: Frank
authors.initials: F
authors.lastname: Burkart
authors.forename: Simone
authors.initials: S
authors.lastname: Ottonello
authors.forename: Martin
authors.initials: M
authors.lastname: Müller
mesh_terms: D000818:Animals; D001426:Bacterial Proteins / Q000235:genetics / Q000378:metabolism; D036022:Capsid Proteins / Q000235:genetics / Q000276:immunology*; D004337:Drug Carriers; D005260:Female; D051379:Mice; D008807:Mice, Inbred BALB C; D010084:Oxidation-Reduction; D053918:Papillomavirus Vaccines / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology*; D055503:Protein Multimerization; D013879:Thioredoxins / Q000235:genetics / Q000378:metabolism*; D014614:Vaccines, Synthetic / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology
chemical_list: D001426:Bacterial Proteins; D036022:Capsid Proteins; D004337:Drug Carriers; D053918:Papillomavirus Vaccines; D014614:Vaccines, Synthetic; D013879:Thioredoxins