Therapeutic Immunization with HIV-1 Peptide-Loaded Dendritic Cells is Safe and Immunogenic in HIV-1-Infected Individuals

University of Pittsburgh School of Medicine, Departments of Medicine, Pathology, and Center for Clinical Pharmacology; Graduate School of Public Health, Departments of Infectious Diseases and Microbiology, University of Pittsburgh Cancer Institute, Pittsburgh, PA; University of Colorado Health Sciences Center: Campus Box B164, 4200 East Ninth Ave, Denver, CO 80262

^* To whom correspondence should be addressed. Email: nancycsc{at}gmail.com.

	Abstract

Background: Treatments for HIV-1+ individuals that augment HIV-1 suppression and have potential for achieving long-term control of HIV-1 viremia in the absence of antiretroviral therapy (ART) are urgently needed. We, therefore, conducted a phase I, clinical safety trial of a dendritic cell (DC)-based vaccination strategy as immunotherapy for HIV-1+ individuals on ART.

Methods: We studied 18 HIV-1+ subjects on antiretroviral therapy (ART) who underwent leukapheresis to obtain PBMC for DC generation from monocytes cultured with cytokines. Mature DC were pulsed with 3 HIV-1, HLA*A0201 Gag, Env and Pol peptides and 1 influenza–A matrix protein (InflA-MP) peptide. The vaccine was administered to donors randomized to receive 2 vaccinations, either IV or SC. The primary end-points were safety and tolerability of two doses of peptide-DC vaccine (3 versus 10 million). Secondary endpoints included IFN-ELISPOT responses and clinical correlates of immune response to vaccination.

Results: Autologous DC-peptide vaccine was safe, well tolerated and feasible in all participants. Adverse events were rare. Although the trial was not powered to assess an immunologic response, significantly increased frequency of HIV-1, peptide-specific IFN-+ cells was observed two weeks following the second vaccine, with 3 individuals responding to all 4 peptides.

Conclusion: DC vaccination was safe, feasible and showed promise of immunogenicity in ART treated, HIV-1+ individuals. Additional studies of DC-immunization strategies for HIV-1 infection are warranted.