Plasmodium falciparum multi-epitope string (PfME)

The Plasmodium falciparum multi-epitope string is a synthetic recombinant construct designed to elicit a broad and potent immune response against the malaria parasite. It typically consists of a linear sequence of multiple immunodominant and highly conserved epitopes derived from various proteins across different stages of the P. falciparum life cycle, such as the circumsporozoite protein (CSP), liver-stage antigen 1 (LSA1), and thrombospondin-related adhesion protein (TRAP) [Hill, 2011, Phil. Trans. R. Soc. B]. The most widely studied version, ME-TRAP, fuses a string of 20 T-cell and B-cell epitopes to the full-length TRAP antigen to maximize the breadth of the immune attack. In clinical development, this multi-epitope string is often delivered using a prime-boost regimen involving viral vectors like Chimpanzee Adenovirus 63 (ChAd63) and Modified Vaccinia Virus Ankara (MVA) [O'Hara et al., 2012, J. Infect. Dis.]. The primary therapeutic goal is to induce high frequencies of antigen-specific T-cells that can recognize and eliminate infected hepatocytes or neutralize sporozoites before they establish a systemic infection. While it has shown significant immunogenicity in clinical trials, achieving high-level, durable sterile protection remains a challenge due to the complex biology of the parasite and the diversity of human immune responses [ClinicalTrials.gov, NCT01623557].

Other names

ME-TRAPMulti-epitope stringPfME-TRAP constructMulti-epitope recombinant antigenMalaria multi-epitope vaccine

The multi-epitope string functions as a synthetic immunogen that presents multiple highly conserved T-cell and B-cell epitopes to the host immune system. When delivered via viral vectors or with adjuvants, it is processed by antigen-presenting cells to stimulate a broad cellular immune response, primarily characterized by the induction of CD8+ and CD4+ T-cells that secrete interferon-gamma (IFN-γ) to target the parasite during its pre-erythrocytic and erythrocytic stages [Ewer et al., 2013, Nature Communications].