Abstract
Objectives: Therapeutic vaccination in chronic HIV-infection aims to attenuate disease progression by promoting new HIV-specific T cell-clones. Most clinical trials with therapeutic vaccines are conducted on patients receiving antiretroviral therapy (ART). However, studies of vaccination in untreated individuals are limited. We present the first data from a phase I/II clinical trial with a peptide-based therapeutic vaccine (Vacc-5q) consisting of five short, modified consensus peptides from p17, p24, and Tat. In addition to evaluating safety and immunogenicity of Vacc-5q, we compared responses induced in patients on effective ART with those of ART-naive patients. Methods: HIV-infected patients stable on ART (n=10) and treatment naive patients (n=10) received 11 intradermal injections of Vacc-5q over 26 weeks, using GM-CSF as an adjuvant. Immunogenicity was assessed both in vivo by delayed type hypersensitivity (DTH) skin tests, and in vitro by T cell activation assays. Persistence of immune responses was retested after 3.5 years. Results: Vacc-5q was found to be immunogenic. Specific T cell-responses both in vivo and in vitro increased significantly from baseline to week 4 (p<0.01), and were still present after 3.5 years. No significant differences were observed between ART treated and ART naive patients at any time point. Conclusion: Vacc-5q induced potent HIV associated cellular immune responses both in ART treated and in treatment-naive viremic patients. These responses were comparably strong in both study arms and still present after 3.5 years, indicating that suppression of plasma viral load by ART might not be essential for optimal immunization.
Highlights
Ineffective immune control of chronic human immunodeficiency virus type-1 (HIV) infection leads to a progressive loss of immune functions and AIDS if not effectively treated [1,2]
Vacc-5q induced potent HIV associated cellular immune responses both in antiretroviral treatment (ART) treated and in treatment-naïve viremic patients. These responses were comparably strong in both study arms and still present after 3.5 years, indicating that suppression of plasma viral load by ART might not be essential for optimal immunization
Vacc-5q consists of altogether five peptides corresponding to Gag (p24 and p17) and Tat consensus sequences; one of the two p24 peptides has been included in another therapeutic vaccine candidate that we have tested previously (Vacc-4x) to allow for the potential to compare immunogenicity [4,10,17,18,19,20]
Summary
Ineffective immune control of chronic human immunodeficiency virus type-1 (HIV) infection leads to a progressive loss of immune functions and AIDS if not effectively treated [1,2]. Vacc-5q consists of altogether five peptides corresponding to Gag (p24 and p17) and Tat consensus sequences; one of the two p24 peptides has been included in another therapeutic vaccine candidate that we have tested previously (Vacc-4x) to allow for the potential to compare immunogenicity [4,10,17,18,19,20]. The objectives in this trial were to evaluate safety and immunogenicity of Vacc-5q.
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