title: DNA prime-protein boost using subtype consensus Env was effective in eliciting neutralizing antibody responses against subtype BC HIV-1 viruses circulating in China.
abstract: Previously, we have shown that DNA prime-protein boost is effective in eliciting neutralizing antibodies (NAb) against randomly selected HIV-1 isolates. Given the genetic diversity of HIV-1 viruses and the unique predominant subtypes in different geographic regions, it is critical to test the DNA prime-protein boost approach against circulating viral isolates in key HIV endemic areas. In the current study, the same DNA prime-protein boost vaccine was used as in previous studies to investigate the induction of NAb responses against HIV-1 clade BC, a major subtype circulating in China. A codon optimized gp120-BC DNA vaccine, based on the consensus envelope (Env) antigen sequence of clade BC, was constructed and a stable CHO cell line expressing the same consensus BC gp120 protein was produced. The immunogenicity of this consensus gp120-BC was examined in New Zealand White rabbits by either DNA prime-protein boost or protein alone vaccination approaches. High levels of Env-specific antibody responses were elicited by both approaches. However, DNA prime-protein boost but not the protein alone immune sera contained significant levels of NAb against pseudotyped viruses expressing HIV-1 BC Env antigens. Furthermore, high frequencies of CD4 binding site-targeted antibodies were found in the DNA prime- protein boost rabbit sera indicating that the positive NAb may be the result of antibodies against conformationally sensitive epitopes on HIV-1 Env. The findings support that DNA prime-protein boost was effective in eliciting NAb against a key HIV-1 virus subtype in China. This result may lead to the development of regional HIV vaccines through this approach.
authors.affiliation: Jiangsu Province Key Laboratory in Infectious Diseases, The First Affiliated Hospital of Nanjing Medical University; Nanjing, China.
authors.forename: Mingshun
authors.initials: M
authors.lastname: Zhang
authors.forename: Lu
authors.initials: L
authors.lastname: Zhang
authors.forename: Chunhua
authors.initials: C
authors.lastname: Zhang
authors.forename: Kunxue
authors.initials: K
authors.lastname: Hong
authors.forename: Yiming
authors.initials: Y
authors.lastname: Shao
authors.forename: Zuhu
authors.initials: Z
authors.lastname: Huang
authors.forename: Shixia
authors.initials: S
authors.lastname: Wang
authors.forename: Shan
authors.initials: S
authors.lastname: Lu
mesh_terms: D016915:AIDS Vaccines / Q000276:immunology*; D000818:Animals; D057134:Antibodies, Neutralizing / Q000276:immunology*; D000917:Antibody Formation / Q000276:immunology*; D015153:Blotting, Western; D016466:CHO Cells; D006224:Cricetinae; D004797:Enzyme-Linked Immunosorbent Assay; D015497:HIV-1 / Q000276:immunology; D011817:Rabbits; D019444:Vaccines, DNA / Q000276:immunology*; D054299:env Gene Products, Human Immunodeficiency Virus / Q000276:immunology*
chemical_list: D016915:AIDS Vaccines; D057134:Antibodies, Neutralizing; D019444:Vaccines, DNA; D054299:env Gene Products, Human Immunodeficiency Virus
keywords: DNA vaccine; HIV-1; neutralizing antibody; prime-boost; subtype BC