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

Abstract

T cell-mediated immune responses against the liver stage of malaria are critical for protection in animal models [1-3]. There is strong evidence for a protective role in humans [4-11]. In animal models of many infectious diseases, DNA vaccination affords protectively immunogenic induction of CD8⁺ and/or CD4⁺ cells [12]. However, several clinical trials have shown that induction of cells by DNA vaccines is suboptimal in humans [13-15]. Heterologous prime-boost vaccination with DNA-based vaccines has appeared to be promising in rodent models [16-19]. Those results provided the rationale for the formulation of clinical grade DNA and viral vaccines recombinant for a malarial DNA sequence designed to induce protective cell immunogenicity against liver-stage Plasmodium falciparummalaria. This DNA sequence is known as multiple epitope (ME)-thrombospondin-related adhesion (or anonymous) protein (TRAP). The ME string contains 14 CD8⁺ cell epitopes, 1 CD4⁺ cell epitope, and 2 cell epitopes from 6 pre-erythrocytic P. falciparumantigens [20]. It also contains 2 nonmalarial CD4⁺ cell epitopes for bystander activation. This is fused in-frame to the entire P. falciparumTRAP [21], to create the hybrid ME-TRAP.