Targeting the vaginal mucosa with human papillomavirus pseudovirion vaccines delivering simian immunodeficiency virus DNA

Shari N. Gordon, Rhonda C. Kines, Galyna Kutsyna, Zhong Min Ma, Anna Hryniewicz, Jeffery N. Roberts, Claudio Fenizia, Rachmat Hidajat, Egidio Brocca-Cofano, Nicolas Cuburu, Christopher B. Buck, Marcelino L. Bernardo, Marjorie Robert-Guroff, Chris J Miller, Barney S. Graham, Douglas R. Lowy, John T. Schiller, Genoveffa Franchini

Research output: Contribution to journalArticle

21 Scopus citations

Abstract

The majority of HIV infections occur via mucosal transmission. Vaccines that induce memory T and B cells in the female genital tract may prevent the establishment and systemic dissemination of HIV.We tested the immunogenicity of a vaccine that uses human papillomavirus (HPV)-based gene transfer vectors, also called pseudovirions (PsVs), to deliver SIV genes to the vaginal epithelium. Our findings demonstrate that this vaccine platform induces gene expression in the genital tract in both cynomolgus and rhesus macaques. Intravaginal vaccination with HPV16, HPV45, and HPV58 PsVs delivering SIV Gag DNA induced Gag-specific Abs in serum and the vaginal tract, and T cell responses in blood, vaginal mucosa, and draining lymph nodes that rapidly expanded following intravaginal exposure to SIV mac251. HPV PsV-based vehicles are immunogenic, which warrant further testing as vaccine candidates for HIV and may provide a useful model to evaluate the benefits and risks of inducing high levels of SIV-specific immune responses at mucosal sites prior to SIV infection.

Original languageEnglish (US)
Pages (from-to)714-723
Number of pages10
JournalJournal of Immunology
Volume188
Issue number2
DOIs
StatePublished - Jan 15 2012

ASJC Scopus subject areas

  • Immunology

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    Gordon, S. N., Kines, R. C., Kutsyna, G., Ma, Z. M., Hryniewicz, A., Roberts, J. N., Fenizia, C., Hidajat, R., Brocca-Cofano, E., Cuburu, N., Buck, C. B., Bernardo, M. L., Robert-Guroff, M., Miller, C. J., Graham, B. S., Lowy, D. R., Schiller, J. T., & Franchini, G. (2012). Targeting the vaginal mucosa with human papillomavirus pseudovirion vaccines delivering simian immunodeficiency virus DNA. Journal of Immunology, 188(2), 714-723. https://doi.org/10.4049/jimmunol.1101404