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

Publication ,  Journal Article
Wright, PF; Mestecky, J; McElrath, MJ; Keefer, MC; Gorse, GJ; Goepfert, PA; Moldoveanu, Z; Schwartz, D; Spearman, PW; El Habib, R; Spring, MD ...
Published in: J Infect Dis
April 1, 2004

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.

Duke Scholars

Published In

J Infect Dis

DOI

ISSN

0022-1899

Publication Date

April 1, 2004

Volume

189

Issue

7

Start / End Page

1221 / 1231

Location

United States

Related Subject Headings

  • Viral Envelope Proteins
  • T-Lymphocytes, Cytotoxic
  • Recombinant Proteins
  • Rabies Vaccines
  • Neutralization Tests
  • Mucous Membrane
  • Middle Aged
  • Microbiology
  • Male
  • Humans
 

Citation

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Wright, P. F., Mestecky, J., McElrath, M. J., Keefer, M. C., Gorse, G. J., Goepfert, P. A., … National Institutes of Allergy and Infectious Diseases AIDS Vaccine Evaluation Group, . (2004). Comparison of systemic and mucosal delivery of 2 canarypox virus vaccines expressing either HIV-1 genes or the gene for rabies virus G protein. J Infect Dis, 189(7), 1221–1231. https://doi.org/10.1086/382088
Wright, Peter F., Jiri Mestecky, M Juliana McElrath, Michael C. Keefer, Geoffrey J. Gorse, Paul A. Goepfert, Zina Moldoveanu, et al. “Comparison of systemic and mucosal delivery of 2 canarypox virus vaccines expressing either HIV-1 genes or the gene for rabies virus G protein.J Infect Dis 189, no. 7 (April 1, 2004): 1221–31. https://doi.org/10.1086/382088.
Wright PF, Mestecky J, McElrath MJ, Keefer MC, Gorse GJ, Goepfert PA, et al. Comparison of systemic and mucosal delivery of 2 canarypox virus vaccines expressing either HIV-1 genes or the gene for rabies virus G protein. J Infect Dis. 2004 Apr 1;189(7):1221–31.
Wright, Peter F., et al. “Comparison of systemic and mucosal delivery of 2 canarypox virus vaccines expressing either HIV-1 genes or the gene for rabies virus G protein.J Infect Dis, vol. 189, no. 7, Apr. 2004, pp. 1221–31. Pubmed, doi:10.1086/382088.
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. Comparison of systemic and mucosal delivery of 2 canarypox virus vaccines expressing either HIV-1 genes or the gene for rabies virus G protein. J Infect Dis. 2004 Apr 1;189(7):1221–1231.
Journal cover image

Published In

J Infect Dis

DOI

ISSN

0022-1899

Publication Date

April 1, 2004

Volume

189

Issue

7

Start / End Page

1221 / 1231

Location

United States

Related Subject Headings

  • Viral Envelope Proteins
  • T-Lymphocytes, Cytotoxic
  • Recombinant Proteins
  • Rabies Vaccines
  • Neutralization Tests
  • Mucous Membrane
  • Middle Aged
  • Microbiology
  • Male
  • Humans