Background:  HAART has led to a dramatic decline in HIV-related morbidity and mortality, but has severe drawbacks. An effective therapeutic vaccine could evoke protective immune responses in HIV-1-infected patients under successful ART, and thus enable HAART interruptions. The potential HIV-1 therapeutic vaccine NYVAC-B evaluated in this study is a recombinant attenuated vaccinia vaccine containing the HIV-1 clade B env gene and gag-pol-nef polygene. Primary objective is to evaluate the safety of NYVAC-B during 12 weeks after the first vaccination; secondary objectives include the evaluation of the HIV-1-specific immune responses.

Methods:  Prior to inclusion we injected 10 HIV-1-infected (clade B) patients, successfully treated with HAART, and whose plasma HIV RNA (pVL) <50 RNA copies/mL, with 1 ml of NYVAC-B IM on week 0 and 4 in the left and right deltoid muscle. Vaccination was followed by 2 hours of clinical observation, and visits on day 1 and weeks 1, 2, 3, 4, 6, 8, 12, 24, 36, and 48. Safety parameters (vaccination-related local and systemic reactions, standard clinical and laboratory parameters, plasma viral load, and CD4/CD8 T-cell counts) are assessed at every visit. HIV-1-specific immune responses are assessed by interferon-γ ELISpot on cryopreserved peripheral blood mononuclear cells at weeks 0, 2, 4, 6, 8, 12, 24, 36, and 48 using 8 pools of HIV-1 peptides encompassing the gag-pol-nef and env regions.

Results:  Safety and immunogenicity analyses until week 12 are presented. After both vaccinations, only grade 1 or 2 local injection-related adverse events were observed. There were no serious adverse events related to the vaccine. CD4 counts and plasma viral load remained very stable over time. Global HIV-1-specific cellular responses (sum of all peptides pools) increased in all 10 patients (median 2.4-fold increase). Considering only >2-fold increased responses as significant, 80% of patients had at least 1 pre-existing response increased after immunization, 70% had ≥2 responses and 50% had ≥5 increased responses. Furthermore, 100% of patients generated ≥1 new response, and 56% generated ≥2 new responses. The responses elicited by NYVAC-B were directed against all 8 peptide pools (gag, pol, nef, and env), but the highest were directed against gag.

Conclusions:  The recombinant HIV-1 vaccine NYVAC-B is safe and well tolerated. Furthermore, it induces vigorous and broad HIV-specific T-cell responses in all vaccinated patients. The clinical efficacy has to be evaluated in a phase II study interrupting HAART after vaccination.