Major histocompatibility complex class I and II molecules loading FP9-PP–derived peptides (MHC-FP9-PP)

The target Major histocompatibility complex class I and II molecules loading FP9-PP–derived peptides refers to the immunological complexes formed when host cells process and present antigens from the FP9-PP vaccine. FP9-PP is a recombinant fowlpox virus vector (strain FP9) engineered to express a synthetic polyprotein (PP), typically the L3SEPTL construct, which includes six pre-erythrocytic antigens from the malaria parasite Plasmodium falciparum: LSA3, STARP, Exp1, Pfs16, TRAP, and LSA1 (1.3.1, 1.4.3). These antigens are intracellularly processed into short peptide fragments and loaded onto MHC Class I and Class II molecules (Human Leukocyte Antigens) for display on the cell surface (1.1.1, 1.4.4). Biologically, these peptide-MHC complexes serve as the essential ligands for T-cell receptors (TCRs). MHC Class I complexes are recognized by CD8+ cytotoxic T cells, while MHC Class II complexes are recognized by CD4+ helper T cells, collectively aiming to induce a protective cellular immune response against the liver stage of malaria (1.1.1, 1.4.2). The primary therapeutic goal of this target is to elicit high frequencies of interferon-gamma (IFN-γ) producing T cells to eliminate infected hepatocytes (1.3.1, 1.4.1). However, clinical development has been hindered by low immunogenicity in human subjects and a lack of significant protective efficacy in challenge trials, potentially due to the complexity and size of the polyprotein insert (1.3.1, 1.3.5).

Other names

MHC-polyprotein complexHLA-L3SEPTL complexFP9-PP peptide-MHC complexMHC-restricted malaria polyprotein antigens

The vaccines act as delivery vehicles for the polyprotein, which is then processed by the host's cellular machinery into peptides. These peptides are loaded onto MHC Class I and II molecules, forming the target complex that is recognized by T-cell receptors to initiate an immune response.