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HIV-1 Gag-specific immunity induced by a lentivector-based vaccine directed to dendritic cells

Dai, Bingbing and Yang, Lili and Yang, Haiguang and Hu, Biliang and Baltimore, David and Wang, Pin (2009) HIV-1 Gag-specific immunity induced by a lentivector-based vaccine directed to dendritic cells. Proceedings of the National Academy of Sciences of the United States of America, 106 (48). pp. 20382-20387. ISSN 0027-8424. PMCID PMC2777969. doi:10.1073/pnas.0911742106.

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Lentivectors (LVs) have attracted considerable interest for their potential as a vaccine delivery vehicle. In this study, we evaluate in mice a dendritic cell (DC)-directed LV system encoding the Gag protein of human immunodeficiency virus (HIV) (LV-Gag) as a potential vaccine for inducing an anti-HIV immune response. The DC-directed specificity is achieved through pseudotyping the vector with an engineered Sindbis virus glycoprotein capable of selectively binding to the DC-SIGN protein. A single immunization by this vector induces a durable HIV Gag-specific immune response. We investigated the antigen-specific immunity and T-cell memory generated by a prime/boost vaccine regimen delivered by either successive LV-Gag injections or a DNA prime/LV-Gag boost protocol. We found that both prime/boost regimens significantly enhance cellular and humoral immune responses. Importantly, a heterologous DNA prime/LV-Gag boost regimen results in superior Gag-specific T-cell responses as compared with a DNA prime/adenovector boost immunization. It induces not only a higher magnitude response, as measured by Gag-specific tetramer analysis and intracellular IFN-γ staining, but also a better quality of response evidenced by a wider mix of cytokines produced by the Gag-specific CD8^+ and CD4^+ T cells. A boosting immunization with LV-Gag also generates T cells reactive to a broader range of Gag-derived epitopes. These results demonstrate that this DC-directed LV immunization is a potent modality for eliciting anti-HIV immune responses.

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URLURL TypeDescription DOIArticle CentralArticle
Baltimore, David0000-0001-8723-8190
Additional Information:© 2009 by the National Academy of Sciences. Contributed by David Baltimore, October 9, 2009 (sent for review August 28, 2009). Published online before print November 16, 2009. Author contributions: B.D., L.Y., D.B., and P.W. designed research; B.D., L.Y., H.Y., and B.H. performed research; B.D., L.Y., D.B., and P.W. analyzed data; and B.D., L.Y., D.B., and P.W. wrote the paper. The authors declare no conflict of interest. Freely available online through the PNAS open access option. We thank Dr. Gary Nabel for providing reagents and Dr. Larry Corey for an initial discussion of the breadth of antigen responses. This research was generously supported by grants from the National Institutes of Health, the Skirball Foundation, and a Grand Challenges in Global Health grant from the Bill and Melinda Gates Foundation. This article contains supporting information online at 0911742106/DCSupplemental.
Funding AgencyGrant Number
Skirball FoundationUNSPECIFIED
Bill and Melinda Gates FoundationUNSPECIFIED
Subject Keywords:AIDS vaccine; human immunodeficiency virus; lentiviral vector; T cell vaccine
Issue or Number:48
PubMed Central ID:PMC2777969
Record Number:CaltechAUTHORS:20091218-143706210
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Official Citation: * Bingbing Dai, * Lili Yang, * Haiguang Yang, * Biliang Hu, * David Baltimore, * and Pin Wang HIV-1 Gag-specific immunity induced by a lentivector-based vaccine directed to dendritic cellsPNAS 2009 106:20382-20387; published online before print November 16, 2009, doi:10.1073/pnas.0911742106
Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:17005
Deposited By: Tony Diaz
Deposited On:05 Jan 2010 22:57
Last Modified:08 Nov 2021 23:31

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