title: Short communication: enhancement of immunogenicity of replication-defective adenovirus-based human immunodeficiency virus vaccines in rhesus monkeys.
abstract: Adenovirus (Ad) is still under extensive investigation as a vector for HIV vaccination; however, one possible explanation for the failure of Merck's STEP trial is the relatively weak immunogenicity of replication-defective Ad vectors. In this study, a novel strategy to enhance the immunogenicity of replication-defective Ad-based HIV vaccines was developed. First, a recombinant plasmid expressing adenoviral E1 protein (pVAX-E1) was constructed to complement the E1-deleted replication-defective Ad vectors in trans. Then, the immunogenicity of the vaccine regimen of Ad5-HIV gag plus pVAX-E1 plasmid was assessed in rhesus macaques. Compared with traditional administration of Ad-based vectors alone, the results showed that our strategy elicited a more sustained and robust HIV gag-specific cellular response and enhanced long-term proliferation of CD4(+) and CD8(+) T lymphocytes. This strategy represents a proof-of-concept that enhances the immunogenicity of replication-defective Ad-based vectors, and it exemplifies the useful implications for Ad-based HIV vaccines and other vaccines.
authors.affiliation: Center for Infection & Immunity, Guangzhou Institute of Biomedicine and Health, Chinese Academy of Sciences, China.
authors.forename: Caijun
authors.initials: C
authors.lastname: Sun
authors.forename: Yinfeng
authors.initials: Y
authors.lastname: Zhang
authors.forename: Yichu
authors.initials: Y
authors.lastname: Liu
authors.forename: Maochao
authors.initials: M
authors.lastname: Zhang
authors.forename: Ling
authors.initials: L
authors.lastname: Chen
mesh_terms: D016915:AIDS Vaccines / Q000235:genetics / Q000276:immunology*; D000256:Adenoviridae / Q000235:genetics*; D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D049109:Cell Proliferation; D004337:Drug Carriers; D005822:Genetic Vectors; D006678:HIV / Q000235:genetics / Q000276:immunology*; D008253:Macaca mulatta; D014614:Vaccines, Synthetic / Q000235:genetics / Q000276:immunology
chemical_list: D016915:AIDS Vaccines; D004337:Drug Carriers; D014614:Vaccines, Synthetic