Dendritic cell‐based therapeutic vaccine elicits polyfunctional HIV‐specific T‐cell immunity associated with control of viral load

Abstract

Eur. J. Immunol. 2014Immunol. . 44: 2802Immunol. -2810 Clinical immunology 2803 IntroductionTo date, no effective therapeutic or prophylactic HIV vaccines are yet available. Recent encouraging results from the RV 144 trial showed a modest but statistically significant 31% reduction in the rate of HIV infection in vaccinated healthy volunteers receiving a prophylactic vaccine [1]. However, immune responses that would eradicate or control HIV are likely to be different from those needed to prevent primary infection. Indeed, eradication of HIV infection is likely to depend on the establishment of strong cytotoxic T lymphocytes, while prevention of infection will likely depend on the establishment of antibodies neutralizing the virus [2,3]. In both cases, CD4 + T helper cells are necessary for the establishment of robust and long-lasting immunity. Several candidate vaccines are under evaluation including peptides, inactivated virus, viral vectors, and ex vivo-generated DCs [4]. The latter represents an approach to optimize the induction of immune responses [5]. To date, only two studies, in which DCs have been loaded with chemically inactivated autologous virus, have reported a decrease in viral load [6,7]. Another approach using DCs transfected with RNA isolated from autologous virus yielded immune responses without control of viral replication [8]. However, these very promising data with inactivated autologous virus still need to be reproduced. For large scale use of DC vaccination, it would be advantageous to identify an antigenic cargo that could be used without having to isolate and expand the autologous virus which necessitates antiretroviral treatment interruption. We report here the safety and immunogenicity of a new DC platform loaded with five HIV-1-derived lipopeptides (LP) [9] in HIV-1-infected patients treated with highly active antiretroviral treatment (HAART). The study design included a 6-month analytical treatment interruption (ATI), a period which allowed us to evaluate the effects of vaccine-elicited immune responses on viral replication (Fig. 1). Results Patients and study outcomesTwenty patients were screened and 19 were enrolled within 17 months. Baseline characteristics of patients are reported in Table 1. All patients received the four vaccinations with no changes in vaccine dose. All patients but one completed the trial at 48 weeks.The vaccination was well tolerated. Two patients reached a safety endpoint (CD4 + T-cell counts below 500 cells/μL) during the vaccination phase while no safety endpoints were observed during the ATI phase. Systemic or local adverse events were mild or moderate (grade 1 or 2) and resolved in less than 2 days in the majority of cases. All patients stopped HAART at 24 weeks post inclusion except two of them who stopped at 25 and 26 weeks.Through 48 weeks, eight patients reached the immunology endpoint defining a failure of the strategy: at 28 (two patients), 32 (three patients), 36, 40, and 44 weeks. Three of these patients resumed HAART. No clinical events or pro...

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