Enhancing efficacy and mucosa-tropic distribution of an oral HIV-PsV DNA vaccine in animal models.
A strategy combined the oral delivery route and bovine papillomavirus (BPV) pseudovirus (PsV)-based human immunodeficiency virus (HIV) DNA vaccine, which has been proven to enhance the mucosal immunization compared with the systemic immunization and in general does not induce effective mucosal immune responses. In this study, the immune responses against the BPV expressing HIV gp41 epitopes (ELDKWA, NWFDIT) after oral administration in Cynomolgus monkeys (Macaca fascicularis) were assessed, and the biodistribution of plasmid DNA encapsulated in the papillomavirus-like particles (VLPs) were evaluated in murine models. Results showed that oral immunization with the HIV-PsV DNA vaccine in monkey generated p24 and gp41 epitopes-specific serum IgG. Importantly, these induced antibodies had been shown to neutralize HIV-1 primary strain. In addition, the advantage of VLPs as vehicles delivering genes had been first revealed in biodistribution results. Therefore, orally administered HIV-PsV DNA vaccine was well-tolerated, enhanced the mucosa targeting property of the plasmid DNA, and reduced the nontargeting distribution, which indicate that it would reduce stress associated with systemic vaccination.
Fu
Jie
J
Department of Pharmacology and Toxicology, Beijing Institute of Radiation Medicine, Beijing, People's Republic of China.
Bian
Guangxing
G
Zhao
Bijun
B
Dong
Zengxiang
Z
Sun
Xiao
X
Chen
Fang
F
Ou
Lun
L
Song
Haifeng
H
D016915:AIDS Vaccines / Q000008:administration & dosage / Q000276:immunology* / Q000493:pharmacokinetics; D000284:Administration, Oral; D000818:Animals; D052688:Bovine papillomavirus 1 / Q000235:genetics*; D002417:Cattle; D005260:Female; D018014:Gene Transfer Techniques; D015700:HIV Envelope Protein gp41 / Q000276:immunology; D018928:Immunity, Mucosal; D007074:Immunoglobulin G / Q000097:blood / Q000276:immunology; D008252:Macaca fascicularis; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D014018:Tissue Distribution; D019444:Vaccines, DNA / Q000008:administration & dosage / Q000276:immunology* / Q000493:pharmacokinetics
D016915:AIDS Vaccines; D015700:HIV Envelope Protein gp41; D007074:Immunoglobulin G; D019444:Vaccines, DNA