title: Oral administration of HPV-16 L2 displayed on Lactobacillus casei induces systematic and mucosal cross-neutralizing effects in Balb/c mice.
abstract: The human papillomavirus (HPV) minor capsid protein, L2, is a good candidate for prophylactic vaccine development because L2-specific antibodies have cross-neutralizing activity against diverse HPV types. Here, we developed a HPV mucosal vaccine candidate using the poly-γ-glutamic acid synthetase A (pgsA) protein to display a partial HPV-16 L2 protein (N-terminal 1-224 amino acid) on the surface of Lactobacillus casei (L. casei). The oral immunization with L. casei-L2 induced productions of L2-specific serum IgG and vaginal IgG and IgA in Balb/c mice. To examine cross-neutralizing activity, we used a sensitive high-throughput neutralization assay based on HPV-16, -18, -45, -58, and bovine papillomavirus 1 (BPV1) pseudovirions. Our results revealed that mice vaccinated with L. casei-L2 not only generated neutralizing antibodies against HPV-16, but they also produced antibodies capable of cross-neutralizing the HPV-18, -45, and -58 pseudovirions. Consistent with previous reports, vaccination with HPV-16 L1 virus-like particles (VLPs) failed to show cross-neutralizing activity. Finally, we found that oral administration of L. casei-L2 induced significant neutralizing activities against genital infection by HPV-16, -18, -45, and -58 pseudovirions encoding a fluorescence reporter gene. These results collectively indicate that oral administration of L2 displayed on L. casei induces systemic and mucosal cross-neutralizing effects in mice.
authors.affiliation: Viral Infectious Disease Research Center, Korea Research Institute of Bioscience and Biotechnology, Daejeon, Republic of Korea.
authors.forename: Sun-Woo
authors.initials: SW
authors.lastname: Yoon
authors.forename: Tae-Young
authors.initials: TY
authors.lastname: Lee
authors.forename: Sung-Jin
authors.initials: SJ
authors.lastname: Kim
authors.forename: Il-Han
authors.initials: IH
authors.lastname: Lee
authors.forename: Moon-Hee
authors.initials: MH
authors.lastname: Sung
authors.forename: Jong-Sup
authors.initials: JS
authors.lastname: Park
authors.forename: Haryoung
authors.initials: H
authors.lastname: Poo
mesh_terms: D000284:Administration, Oral; D000818:Animals; D057134:Antibodies, Neutralizing / Q000032:analysis* / Q000097:blood; D000914:Antibodies, Viral / Q000032:analysis* / Q000097:blood; D001426:Bacterial Proteins / Q000235:genetics; D001769:Blood / Q000276:immunology; D036022:Capsid Proteins / Q000235:genetics / Q000276:immunology*; D004337:Drug Carriers; D005260:Female; D005822:Genetic Vectors; D018928:Immunity, Mucosal; D007070:Immunoglobulin A / Q000032:analysis / Q000097:blood; D007074:Immunoglobulin G / Q000032:analysis / Q000097:blood; D007780:Lacticaseibacillus casei / Q000201:enzymology / Q000235:genetics*; D051379:Mice; D008807:Mice, Inbred BALB C; D009500:Neutralization Tests / Q000379:methods; D009856:Oncogene Proteins, Viral / Q000235:genetics / Q000276:immunology*; D053918:Papillomavirus Vaccines / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology*; D010453:Peptide Synthases / Q000235:genetics; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000276:immunology; D014614:Vaccines, Synthetic / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology; D014621:Vagina / Q000276:immunology
chemical_list: D057134:Antibodies, Neutralizing; D000914:Antibodies, Viral; D001426:Bacterial Proteins; D036022:Capsid Proteins; D004337:Drug Carriers; D007070:Immunoglobulin A; D007074:Immunoglobulin G; C063316:L2 protein, Human papillomavirus type 16; D009856:Oncogene Proteins, Viral; D053918:Papillomavirus Vaccines; D011993:Recombinant Fusion Proteins; D014614:Vaccines, Synthetic; D010453:Peptide Synthases; C445299:gamma-polyglutamic acid synthetase