Therapeutic immunization with a human immunodeficiency virus (HIV) type 1-recombinant canarypox vaccine in chronically HIV-infected patients: The Vacciter Study (ANRS 094)

Expansion and Diversification of Virus-Specific T Cells following Immunization of Human Immunodeficiency Virus Type 1 (HIV-1)-Infected Individuals with a Recombinant Modified Vaccinia Virus Ankara/HIV-1 Gag Vaccine

“…The immunogenicity of recombinant MVA that we observed is particularly impressive when considering the following: (i) the study cohort comprised patients with more advanced disease (median pre-HAART CD4 T-cell nadir, 180 cells/l) than those included in previously reported studies (19,21,32,39,40); (ii) the dose of MVA was modest compared with previous human and nonhuman primate studies (8,16,33,41); and (iii) the sequence of the immunogen is based on the clade A consensus sequence (14), whereas the majority of vaccinees were known to be infected with other subtypes (data not shown). Furthermore, HIV-1 infection per se did not appear to inhibit the generation of responses to MVA.HIVA despite the potential for immune interference (36).…”

“…It is not known whether induction of virus-specific lymphoproliferative responses by vaccination can enhance virological control, but this is suggested by clinical trials and by inference from studies of individuals who maintain low virus loads without therapy (5,21,39,42). We therefore analyzed the capacity of CD8 ϩ and CD4 ϩ T cells to proliferate in response to overlapping Gag peptides in a 6-day CFSE assay.…”

“…Vaccination during HAART has therefore been proposed as a strategy to boost these responses before reexposure to the virus (3). In this context, immunization with live attenuated poxvirus-vectored vaccines or plasmid DNA expressing HIV proteins (8,11,16,19,21,39) or inactivated envelope-depleted HIV-1 (32) can elicit new cellular immune responses or amplify preexisting responses to HIV-1. However, it is not known whether responses stimulated by these vaccines will be more effective than those elicited by natural infection, as this has not been fully addressed.…”

Immunisation with recombinant modified vaccinia virus Ankara expressing HIV‐1 gag in HIV‐1‐infected subjects stimulates broad functional CD4+ T cell responses

“…Other therapeutic vaccination studies have shown that recombinant canarypox expressing HIV-1 proteins or with inactivated envelope-depleted HIV-1 could augment virus-specific IFN-c-secreting CD4 + T cells and/or CD4 + T cell proliferative responses in HAARTtreated subjects [21,[38][39][40], but the cytokine expression profile of responding cells was not examined. Since progression of HIV-1 infection is accompanied by a shift in cytokine expression of virus-specific CD4 + T cells from a polyfunctional response to production of IFN-c only, with variable restoration of functions during HAART, we sought to investigate possible effects of MVA.HIVA vaccinations on these parameters [5,41].…”

“…While there is now substantial evidence that MVAvectored vaccines expressing antigens from pathogens other than HIV-1 can efficiently expand primed CD4 + T cells in HIV-uninfected human subjects [25,34,35], our data suggest that MVA.HIVA vaccination can stimulate HIV-1-specific T helper responses to a greater array of epitopes than those targeted by CD4 + T cells during chronic infection. In contrast, in earlier studies involving therapeutic vaccinations with an MVA vaccine expressing the HIV-1 nef gene, cellular responses to nef epitopes were boosted by immunisation but generated conflicting results with regard to amplification of T helper responses [36,37].Other therapeutic vaccination studies have shown that recombinant canarypox expressing HIV-1 proteins or with inactivated envelope-depleted HIV-1 could augment virus-specific IFN-c-secreting CD4 + T cells and/or CD4 + T cell proliferative responses in HAARTtreated subjects [21,[38][39][40], but the cytokine expression profile of responding cells was not examined. Since progression of HIV-1 infection is accompanied by a shift in cytokine expression of virus-specific CD4 + T cells from a polyfunctional response to production of IFN-c only, with variable restoration of functions during HAART, we sought to investigate possible effects of MVA.HIVA vaccinations on these parameters [5,41].…”