Comparison of systemic and mucosal delivery of 2 canarypox virus vaccines expressing either HIV-1 genes or the gene for rabies virus G protein.

Published

Journal Article

BACKGROUND: Since the primary routes of human immunodeficiency type 1 (HIV-1) infection are across mucosal barriers, a randomized trial of canarypox virus-based vectors was conducted in 84 individuals, with delivery of vaccine by mucosal routes, and was accompanied by a detailed analysis of humoral, cellular, and mucosal immune responses. METHODS: Over the course of 6 months, HIV-1-specific (vCP 205) and rabies (vCP 65) canarypox virus vectors were delivered systemically and/or mucosally into the nose, mouth, vagina, or rectum in a 4-dose schedule, followed by 2 doses of HIV-1 MN recombinant glycoprotein (rgp) 120 or subunit rabies vaccine administered by the intramuscular route. RESULTS: Administration of vaccine and collection of samples were well tolerated. Serum IgG HIV-1-specific antibodies to rgp120 were rarely seen after either systemic or mucosal delivery of canarypox virus vaccine. In contrast, serum IgG rabies and canarypox antibodies were detected in all individuals after systemic, but rarely after mucosal, delivery of vaccine. Suggestions of mucosal recognition of HIV-1 antigen included a cytotoxic T lymphocyte response in 4 of 8 individuals after administration of vaccine by the intrarectal route and a limited immunoglobulin A response at the same site. CONCLUSIONS: Each of the routes of vaccine administration was feasible in the context of a phase 1 study with motivated individuals. However, with the doses and routes of administration used, canarypox virus was not an effective mucosal immunogen.

Full Text

Duke Authors

Cited Authors

  • Wright, PF; Mestecky, J; McElrath, MJ; Keefer, MC; Gorse, GJ; Goepfert, PA; Moldoveanu, Z; Schwartz, D; Spearman, PW; El Habib, R; Spring, MD; Zhu, Y; Smith, C; Flores, J; Weinhold, KJ; National Institutes of Allergy and Infectious Diseases AIDS Vaccine Evaluation Group,

Published Date

  • April 2004

Published In

Volume / Issue

  • 189 / 7

Start / End Page

  • 1221 - 1231

PubMed ID

  • 15031791

Pubmed Central ID

  • 15031791

Electronic International Standard Serial Number (EISSN)

  • 1537-6613

International Standard Serial Number (ISSN)

  • 0022-1899

Digital Object Identifier (DOI)

  • 10.1086/382088

Language

  • eng