A phase I/IIa immunotherapy trial of HIV-1-infected patients with Tat, Rev and Nef expressing dendritic cells followed by treatment interruption
In a phase I/IIa clinical trial, 17 HIV-1 infected patients, stable on cART, received 4 vaccinations with autologous dendritic cells electroporated with mRNA encoding Tat, Rev and Nef, after which cART was interrupted. Vaccination was safe and feasible. During the analytical treatment interruption (ATI), no serious adverse events were observed. Ninety-six weeks following ATI, 6/17 patients remained off therapy. Although induced and/or enhanced CD4+and CD8+T-cell responses specific for the immunogens were observed in most of the patients, we found no correlation with the number of weeks off cART. Moreover, CD4+T-cell counts, plasma viral load and the time remaining off cART following ATI did not differ from historical control data. To conclude, the vaccine was safe, well tolerated and resulted in vaccine-specific immune responses. Since no correlation with clinical parameters could be found, these results warrant further research in order to optimize the efficacy of vaccine-induced T-cell responses.
|Keywords||Dendritic cells, Early expressed proteins, HIV-1, T-cell responses, Therapeutic vaccination|
|Persistent URL||dx.doi.org/10.1016/j.clim.2011.10.010, hdl.handle.net/1765/31846|
Allard, S.D., de Keersmaecker, B., de Goede, A.L., Verschuren, E.J., Koetsveld, J., Reedijk, M.L., … Gruters, R.A.. (2012). A phase I/IIa immunotherapy trial of HIV-1-infected patients with Tat, Rev and Nef expressing dendritic cells followed by treatment interruption. Clinical Immunology, 142(3), 252–268. doi:10.1016/j.clim.2011.10.010