Details

Autor(en) / Beteiligte

• Dai, Bingbing
• Yang, Lili
• Yang, Haiguang
• Hu, Biliang
• Baltimore, David
• Wang, Pin

Titel

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

Ist Teil von

• Proceedings of the National Academy of Sciences - PNAS, 2009-12, Vol.106 (48), p.20382-20387

Ort / Verlag

United States: National Academy of Sciences

Erscheinungsjahr

2009

Quelle

MEDLINE

Beschreibungen/Notizen

• 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.