Therapeutic Vaccination Using Cationic Liposome-Adjuvanted HIV Type 1 Peptides Representing HLA-Supertype-Restricted Subdominant T Cell Epitopes: Safety, Immunogenicity, and Feasibility in Guinea-Bissau

Abstract

We have designed a therapeutic HIV-1 vaccine concept based on peptides together with the adjuvant CAF01. Peptides represented 15 HLA-supertype-restricted subdominant and conserved CD8 T cell epitopes and three CD4 T-helper cell epitopes. In this phase I clinical trial, safety and immunogenicity were assessed in untreated HIV-1-infected individuals in Guinea-Bissau, West Africa. Twenty-three HIV-1-infected individuals were randomized to receive placebo (n=5) or vaccine (n=18). Safety was appraised by clinical follow-up combined with monitoring of biochemistry, hematology, CD4 T cell counts, and HIV-1 viral loads. T cell immunogenicity was monitored longitudinally by interferon (IFN)-γ ELISpot. New vaccine-specific T cell responses were induced in 6/14 vaccinees for whom ELISpot data were valid. CD4 T cell counts and viral loads were stable. The study shows that therapeutic immunization is feasible and safe in Guinea-Bissau and that it is possible to redirect T cell immunity with CAF01-adjuvanted HIV-1 peptide vaccine during untreated HIV-1 infection in some patients. However, relatively few preexisting and vaccine-induced HIV-1 T cell responses to CD8 T cell epitopes were detected against HIV-1 using IFN-γ ELISpot in this chronically infected African population.

Trehalose diester glycolipids are superior to the monoesters in binding to Mincle, activation of macrophages in vitro and adjuvant activity in vivo

“…4 In addition, CAF01 has been tested successfully in phase I clinical trials in combination with the recombinant tuberculosis fusion antigen Ag85B-ESAT6 (H1) (NCT ID: NCT00922363) and an HIV-1 peptide mix (NCT ID: NCT01141205; NCT01009762), and it was found to induce long-lasting cellular immune responses. 5,6 TDB activates primary human APCs by binding to Mincle, thereby triggering chemokine and cytokine production via Syk-Card9 signalling, indicating that the mode of signalling is conserved between mice and humans. 7 …”

Influence of trehalose 6,6′-diester (TDX) chain length on the physicochemical and immunopotentiating properties of DDA/TDX liposomes

“…Induction of cell-mediated immunity is a prerequisite for preventing diseases such as tuberculosis, malaria and AIDS. CAF01 has been tested in phase 1 clinical trials in combination with the recombinant tuberculosis fusion antigen Ag85B-ESAT6 (NCT ID: NCT00922363) and an HIV-1 peptide mix (NCT ID: NCT01141205; NCT01009762), and has been shown to be safe and well-tolerated [15].…”

Inducing Dose Sparing with Inactivated Polio Virus Formulated in Adjuvant CAF01

“…CAF01 has proven to enhance both humoral and cell-mediated memory immune responses to a number of different experimental vaccine candidates [17][18][19] in preclinical models. CAF01 has furthermore already been tested in three phase-I trials with an excellent safety and immunogenicity profile (EAG, personal communications and [20][21][22]). Additionally, CAF01 was also found to provide dose-sparing when used in a combination with the trivalent influenza split vaccine in ferrets [23].…”