A dendritic cell targeted vaccine induces long-term HIV-specific immunity within the gastrointestinal tract

D. Ruane, Y. Do, L. Brane, A. Garg, L. Bozzacco, T. Kraus, M. Caskey, A. Salazar, C. Trumpheller, S. Mehandru

Research output: Contribution to journalArticlepeer-review

19 Scopus citations

Abstract

Despite significant therapeutic advances for HIV-1 infected individuals, a preventative HIV-1 vaccine remains elusive. Studies focusing on early transmission events, including the observation that there is a profound loss of gastrointestinal (GI) CD4+ T cells during acute HIV-1 infection, highlight the importance of inducing HIV-specific immunity within the gut. Here we report on the generation of cellular and humoral immune responses in the intestines by a mucosally administered, dendritic cell (DC) targeted vaccine. Our results show that nasally delivered α-CD205-p24 vaccine in combination with polyICLC, induced polyfunctional immune responses within naso-pulmonary lymphoid sites that disseminated widely to systemic and mucosal (GI tract and the vaginal epithelium) sites. Qualitatively, while α-CD205-p24 prime-boost immunization generated CD4+ T-cell responses, heterologous prime-boost immunization with α-CD205-p24 and NYVAC gag-p24 generated high levels of HIV-specific CD4+ and CD8+ T cells within the GI tract. Finally, DC-targeting enhanced the amplitude and longevity of vaccine-induced immune responses in the GI tract. This is the first report of a nasally delivered, DC-targeted vaccine to generate HIV-specific immune responses in the GI tract and will potentially inform the design of preventative approaches against HIV-1 and other mucosal infections.

Original languageEnglish
Pages (from-to)1340-1352
Number of pages13
JournalMucosal Immunology
Volume9
Issue number5
DOIs
StatePublished - 1 Sep 2016

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