Phase 1 Evaluation of 3 Highly Immunogenic Prime-Boost Regimens, Including a 12-Month Reboosting Vaccination, for Malaria Vaccination in Gambian Men

    loading  Checking for direct PDF access through Ovid

Abstract

Successful vaccination against intracellular pathogens, including liver-stagePlasmodium falciparum,will require induction of strong antigen-specific lymphocyte responses. The multiple epitope (ME)-thrombospon-din-related adhesion protein (TRAP) construct includes CD8+ and CD4+ cell epitopes from pre-erythrocyticP. falciparumantigens fused in-frame to the entire pre-erythrocytic antigen TRAP. Three carriers for this constructplasmid DNA and 2 recombinant nonreplicating poxviruses (modified vaccinia virus Ankara [MVA] and fowlpox strain 9 [FP9])were administered at 3-week intervals in a heterologous prime-boost combination to 29 Gambian men aged 18-45 years. Doses of DNA -TRAP, MVA -TRAP, and FP9 -TRAP were 2 mg and 1.5 X 108 and 1 X 108 plaque-forming units, respectively. DNA -TRAP was injected intramuscularly; MVA -TRAP and FP9 -TRAP were injected intradermally. There were no clinically relevant laboratory abnormalities and no severe or serious adverse events related to vaccination. DNA/MVA and FP9/MVA regimens were the most potent inducers of circulating effector cells seen to date in sub-Saharan Africa. Twelve months after the final vaccination, a single booster vaccination expanded the effector cell pool to a similar or higher magnitude than that after the primary vaccinations. These results highlight optimized combination regimens with general relevance to the development of vaccines targeting intracellular pathogens.

Related Topics

    loading  Loading Related Articles