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208 Oligo-Arginine-Conjugated HIV-1 gag Induces Specific T-Cell Responses in HIV-Infected and Uninfected Individuals
S. K. Kundu-Raychaudhuri*1, J. Rothbard2, E. Engleman1, and T. C. Merigan1
1Stanford Univ. Med. Ctr., CA, USA and 2Cellgate Inc., Sunnyvale, CA, USA
Background: Short oligomers of arginine efficiently transport macromolecules into the cytosol of most cells. This unique property was applied to solve the problem of using proteins as immunogens to induce T-cell responses. HIV-specific CTL and Th1 cytokines, IFN-gamma and IL-2, play important roles in controlling HIV infection. We have studied the effect of oligo-arginine conjugation to HIV-1 gag in induction of gag-specific CTL, IFN-gamma, and IL-2 production in HIV-infected and uninfected individuals.
Methods: 15 HIV(+) and 10 HIV(() individuals were included in this study. Dendritic cells (DC), potent APC were obtained from blood monocytes cultured with GM-CSF and IL-4. DC were pulsed with gag, gag-R7 (oligo-arginine conjugated gag). Autologous T cells were cultured with antigen-pulsed DC (DC:T cell = 1:10). IFN-gamma, IL-2 production were assessed by ELISA of the culture supernatants after 48 h of incubation. CTL were measured by ELISPOT and 51-Cr release assay.
Results: IFN-gamma and IL-2 production, as well as CTL activities were significantly higher after gag-R7 stimulation (p < 0.001, Student’s t-test) as compared with gag stimulation. Similar results were obtained using antigen-pulsed DC obtained by leukapheresis. The response profiles were similar in both HIV(+) and HIV(() individuals.
Conclusions:Thus, the DC-based antigen presentation and oligo-arginine-based delivery system provides a potentially novel approach to improve immunogenicity both in prophylactic and therapeutic vaccination strategies for HIV infection.
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