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Efforts aimed at restoring robust immune responses limiting human immunodeficiency virus (HIV)-1 replication therapeutically are warranted. We report that vaccination with dendritic cells generated ex vivo and loaded with HIV lipopeptides in patients (n = 19) on antiretroviral therapy was well tolerated and immunogenic. Vaccination increased: (i) the breadth of the immune response from 1 (1-3) to 4 (2-5) peptide-pool responses/patient (p = 0.009); (ii) the frequency of functional T cells (producing at least two cytokines among IFN-γ, TNF-α, and IL-2) from 0.026 to 0.32% (p = 0.002) and from 0.26 to 0.35% (p = 0.005) for CD4(+) and CD8(+) T cells, respectively; and (iii) the breadth of cytokines secreted by PBMCs upon antigen exposure, including IL-2, IFN-γ, IL-21, IL-17, and IL-13. Fifty percent of patients experienced a maximum of viral load (VL) 1 log10 lower than the other half following antiretroviral treatment interruption. An inverse correlation was found between the maximum of VL and the frequency of polyfunctional CD4(+) T cells (p = 0.007), production of IL-2 (p = 0.006), IFN-γ (p = 0.01), IL-21 (p = 0.006), and IL-13 (p = 0.001). These results suggest an association between vaccine responses and a better control of viral replication. These findings will help in the development of strategies for a functional cure for HIV infection., (© 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

One goal of HIV vaccination is to achieve high mucosal levels of specific secretory IgA (SIgA). In order to elicit specific SIgA antibodies against human immunodeficiency virus type-1 (HIV-1), a vaccine must be administered by the mucosal route, to the nasal or vaginal mucosa for example. We report here the results of the first phase I, randomized, open-label trial designed to assess the mucosal tolerability and immunogenicity of a candidate vaccine (recombinant protein HIV-1 gp160MN/LAI with or without DC-Chol adjuvant) administered by the nasal or vaginal route. Thirty-four female volunteers with a mean age of 46 years were vaccinated. There were 465 adverse events, of which 65 were considered related to the vaccine. No severe adverse events were related to the vaccine, and no difference in terms of tolerability was observed between the sites of vaccination or between the vaccine formulations. None of the volunteers reported that study participation affected their intimate or broader social relationships. No anti-gp160 activity was found between week 4 and week 48 in serum, saliva, or cervicovaginal and nasal secretions. These results show that a mucosal HIV vaccine can be well tolerated when administered by the nasal or vaginal route.