title: Immunogenicity of bivalent human papillomavirus DNA vaccine using human endogenous retrovirus envelope-coated baculoviral vectors in mice and pigs.
abstract: Human papillomavirus is known to be the major pathogen of cervical cancer. Here, we report the efficacy of a bivalent human papillomavirus type 16 and 18 DNA vaccine system following repeated dosing in mice and pigs using a recombinant baculovirus bearing human endogenous retrovirus envelope protein (AcHERV) as a vector. The intramuscular administration of AcHERV-based HPV16L1 and HPV18L1 DNA vaccines induced antigen-specific serum IgG, vaginal IgA, and neutralizing antibodies to levels comparable to those achieved using the commercially marketed vaccine Cervarix. Similar to Cervarix, AcHERV-based bivalent vaccinations completely blocked subsequent vaginal challenge with HPV type-specific pseudovirions. However, AcHERV-based bivalent vaccinations induced significantly higher cell-mediated immune responses than Cervarix, promoting 4.5- (HPV16L1) and 3.9-(HPV18L1) fold higher interferon-γ production in splenocytes upon stimulation with antigen type-specific pseudovirions. Repeated dosing did not affect the immunogenicity of AcHERV DNA vaccines. Three sequential immunizations with AcHERV-HP18L1 DNA vaccine followed by three repeated dosing with AcHERV-HP16L1 over 11 weeks induced an initial production of anti-HPV18L1 antibody followed by subsequent induction of anti-HPV16L1 antibody. Finally, AcHERV-based bivalent DNA vaccination induced antigen-specific serum IgG immune responses in pigs. These results support the further development of AcHERV as a bivalent human papillomavirus DNA vaccine system for use in preventing the viral infection as well as treating the infected women by inducing both humoral and cell-mediated immune responses. Moreover, the possibility of repeated dosing indicates the utility of AcHERV system for reusable vectors of other viral pathogen vaccines.
authors.affiliation: College of Animal Bioscience & Technology, Konkuk University, Seoul, South Korea.
authors.forename: Hee-Jung
authors.initials: HJ
authors.lastname: Lee
authors.forename: Yoon-Ki
authors.initials: YK
authors.lastname: Hur
authors.forename: Youn-Dong
authors.initials: YD
authors.lastname: Cho
authors.forename: Mi-Gyeong
authors.initials: MG
authors.lastname: Kim
authors.forename: Hoon-Taek
authors.initials: HT
authors.lastname: Lee
authors.forename: Yu-Kyoung
authors.initials: YK
authors.lastname: Oh
authors.forename: Young Bong
authors.initials: YB
authors.lastname: Kim
mesh_terms: D000818:Animals; D016367:Baculoviridae / Q000235:genetics; D020077:Endogenous Retroviruses / Q000235:genetics* / Q000378:metabolism; D004797:Enzyme-Linked Immunosorbent Assay / Q000379:methods; D005260:Female; D005822:Genetic Vectors; D049452:Green Fluorescent Proteins / Q000378:metabolism; D052162:Human papillomavirus 16 / Q000378:metabolism; D052161:Human papillomavirus 18 / Q000378:metabolism; D006801:Humans; D051379:Mice; D008807:Mice, Inbred BALB C; D009500:Neutralization Tests; D053918:Papillomavirus Vaccines / Q000276:immunology* / Q000378:metabolism; D012190:Retroviridae / Q000235:genetics*; D013552:Swine; D019444:Vaccines, DNA / Q000378:metabolism*
chemical_list: D053918:Papillomavirus Vaccines; D019444:Vaccines, DNA; C510352:human papillomavirus vaccine, L1 type 16, 18; D049452:Green Fluorescent Proteins