title: Sublingual immunization of trivalent human papillomavirus DNA vaccine in baculovirus nanovector for protection against vaginal challenge.
abstract: Here, we report the immunogenicity of a sublingually delivered, trivalent human papillomavirus (HPV) DNA vaccine encapsidated in a human endogenous retrovirus (HERV) envelope-coated, nonreplicable, baculovirus nanovector. The HERV envelope-coated, nonreplicable, baculovirus-based DNA vaccine, encoding HPV16L1, -18L1 and -58L1 (AcHERV-triHPV), was constructed and sublingually administered to mice without adjuvant. Following sublingual (SL) administration, AcHERV-triHPV was absorbed and distributed throughout the body. At 15 minutes and 1 day post-dose, the distribution of AcHERV-triHPV to the lung was higher than that to other tissues. At 30 days post-dose, the levels of AcHERV-triHPV had diminished throughout the body. Six weeks after the first of three doses, 1×10(8) copies of SL AcHERV-triHPV induced HPV type-specific serum IgG and neutralizing antibodies to a degree comparable to that of IM immunization with 1×10(9) copies. AcHERV-triHPV induced HPV type-specific vaginal IgA titers in a dose-dependent manner. SL immunization with 1×10(10) copies of AcHERV-triHPV induced Th1 and Th2 cellular responses comparable to IM immunization with 1×10(9) copies. Molecular imaging revealed that SL AcHERV-triHPV in mice provided complete protection against vaginal challenge with HPV16, HPV18, and HPV58 pseudoviruses. These results support the potential of SL immunization using multivalent DNA vaccine in baculovirus nanovector for induction of mucosal, systemic, and cellular immune responses.
authors: Department of Bio-industrial Technologies, Konkuk University, Seoul, Republic of Korea.
authors: Hee-Jung
authors: HJ
authors: Lee
authors: Department of Bio-industrial Technologies, Konkuk University, Seoul, Republic of Korea.
authors: Hansam
authors: H
authors: Cho
authors: College of Pharmacy and Research Institute of Pharmaceutical Sciences, Seoul National University, Seoul, Republic of Korea.
authors: Mi-Gyeong
authors: MG
authors: Kim
authors: Department of Bio-industrial Technologies, Konkuk University, Seoul, Republic of Korea.
authors: Yoon-Ki
authors: YK
authors: Heo
authors: Department of Bio-industrial Technologies, Konkuk University, Seoul, Republic of Korea.
authors: Yeondong
authors: Y
authors: Cho
authors: Department of Bio-industrial Technologies, Konkuk University, Seoul, Republic of Korea.
authors: Yong-Dae
authors: YD
authors: Gwon
authors: Department of Bio-industrial Technologies, Konkuk University, Seoul, Republic of Korea.
authors: Ki Hoon
authors: KH
authors: Park
authors: College of Pharmacy and Research Institute of Pharmaceutical Sciences, Seoul National University, Seoul, Republic of Korea.
authors: Hyerim
authors: H
authors: Jin
authors: College of Pharmacy and Research Institute of Pharmaceutical Sciences, Seoul National University, Seoul, Republic of Korea.
authors: Jinyoung
authors: J
authors: Kim
authors: College of Pharmacy and Research Institute of Pharmaceutical Sciences, Seoul National University, Seoul, Republic of Korea.
authors: Yu-Kyoung
authors: YK
authors: Oh
authors: Department of Bio-industrial Technologies, Konkuk University, Seoul, Republic of Korea.
authors: Young Bong
authors: YB
authors: Kim
mesh_terms: D000286:Administration, Sublingual; D000818:Animals; D016367:Baculoviridae / Q000235:genetics; D036022:Capsid Proteins / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology; D005260:Female; D005822:Genetic Vectors; D052162:Human papillomavirus 16 / Q000235:genetics / Q000276:immunology; D052161:Human papillomavirus 18 / Q000235:genetics / Q000276:immunology; D006801:Humans; D007111:Immunity, Cellular / Q000187:drug effects*; D051379:Mice; D030361:Papillomavirus Infections / Q000276:immunology* / Q000517:prevention & control; D053918:Papillomavirus Vaccines / Q000008:administration & dosage* / Q000276:immunology; D019444:Vaccines, DNA / Q000008:administration & dosage* / Q000276:immunology; D014621:Vagina / Q000187:drug effects / Q000276:immunology
chemical_list: D036022:Capsid Proteins; D053918:Papillomavirus Vaccines; D019444:Vaccines, DNA