The use of a P. falciparum specific coiled-coil domain to construct a self-assembling protein nanoparticle vaccine to prevent malaria

Abstract

Background:The parasitic disease malaria remains a major global public health concern and no truly effective vaccine exists. One approach to the development of a malaria vaccine is to target the asexual blood stage that results in clinical symptoms. Most attempts have failed. New antigens such as P27A and P27 have emerged as potential new vaccine candidates. Multiple studies have demonstrated that antigens are more immunogenic and are better correlated with protection when presented on particulate delivery systems. One such particulate delivery system is the self-assembling protein nanoparticle (SAPN) that relies on coiled-coil domains of proteins to form stable nanoparticles. In the past we have used de novo designed amino acid domains to drive the formation of the coiled-coil scaffolds which present the antigenic epitopes on the particle surface. Results:Here we use naturally occurring domains found in the tex1 protein to form the coiled-coil scaffolding of the nanoparticle. Thus, by engineering P27A and a new extended form of the coiled-coil domain P27 onto the N and C terminus of the SAPN protein monomer we have developed a particulate delivery system that effectively displays both antigens on a single particle that uses malaria tex1 sequences to form the nanoparticle scaffold. These particles are immunogenic in a murine model and induce immune responses similar to the ones observed in seropositive individuals in malaria endemic regions. Conclusions:We demonstrate that our P27/P27A-SAPNs induce an immune response akin to the one in seropositive individuals in Burkina Faso. Since P27 is highly conserved among different Plasmodium species, these novel SAPNs may even provide cross-protection between Plasmodium falciparum and Plasmodium vivax the two major human malaria pathogens. As the SAPNs are also easy to manufacture and store they can be delivered to the population in need without complication thus providing a low cost malaria vaccine.

Production of <em>E. coli</em>-expressed Self-Assembling Protein Nanoparticles for Vaccines Requiring Trimeric Epitope Presentation

“…SAPNs are based on coiled-coil domains and are traditionally expressed in Escherichia coli 8 . SAPN vaccine candidates have been developed for a variety of diseases such as malaria, SARS, influenza, toxoplasmosis, and HIV-1 9,10,11,12,13,14,15,16,17,18,19 . The design of each SAPN candidate is specific to the pathogen of interest, however, the production, purification, and refolding techniques are generally broadly applicable.…”

Designing self-assembled peptide nanovaccine against Streptococcus pneumoniae: An in silico strategy

“…In the context of SAPN formation mechanism, two α-helical coiled-coil domains, the pentameric coiled-coils that is derived from an N-terminal peptide of cartilage oligomeric matrix protein, and the trimeric coiled-coils that are made through de novo designed C-terminal leucine zipper peptide are linked by two glycine residues to form higher-order nanoparticles; these domains are self-assembled by a combination of hydrophobic and electrostatic interactions existing within the residues of coiled-coil domains [64,65]. In recent years, different SAPN-based vaccines have been designed and evaluated against various pathogens, including Toxoplasma gondii, human immunodeficiency viruses (HIV), Plasmodium falciparum, severe acute respiratory syndrome (SARS) coronavirus [66][67][68][69][70][71]. Although Chen et al study, showed the trivalent antigen combination of YLN (protective peptide epitopes from CbpA) and L460D (fragment of PspA) as epitope vaccine elicited the strong and broad protection in diverse pneumococcal challenge models [72], but there isn't any report on the production of epitope-based SAPN vaccine against S. pneumoniae.…”

Investigating the Characteristics and Evolution of Apical Membrane Antigen 1 (AMA1) of Plasmodium sp. using Phylogenetic Approach in Searching for Drug Candidate

“…3). [28], [29]. Surprisingly, the InterPro analysis didn't show any coil region in the P. falciparum but it had a disordered region in the cytoplasmic domain.…”