Functionally Relevant Proteins in Plasmodium Falciparum Host Cell Invasion

Abstract

A totally effective, antimalarial vaccine must involve sporozoite and merozoite proteins (or their fragments) to ensure complete parasite blocking during critical invasion stages. This Special Report examines proteins involved in critical biological functions for parasite survival and highlights the conserved amino acid sequences of the most important proteins involved in sporozoite invasion of hepatocytes and merozoite invasion of red blood cells. Conserved high activity binding peptides are located in such proteins' functionally strategic sites, whose functions are related to receptor binding, nutrient and protein transport, enzyme activity and molecule-molecule interactions. They are thus excellent targets for vaccine development as they block proteins binding function involved in invasion and also their biological function.

Conserved Binding Regions Provide the Clue for Peptide-Based Vaccine Development: A Chemical Perspective

“…Our results showed that the parasite avoids the immune response by using conserved aa sequences to perform critical biological functions. Although these sequences are available for the immune system, they are immunologically silent due to the particular and specific 3D structure they adopt [ 123 , 124 ]. Furthermore, protein 3D studies have shown that parasite cHABPs from the most functionally-relevant structures involved in host cell invasion are craftily located far away from highly polymorphic and immunogenic regions to distract the immune response [ 79 ].…”

Specific β-Turns Precede PPIIL Structures Binding to Allele-Specific HLA-DRβ1* PBRs in Fully-Protective Malaria Vaccine Components

“…Our group found that a specific group of immune protection-inducing protein structure (IMPIPS, involving LLPI and SPI) had or contained PPII L -like structures in our search for a logical and rational methodology for malaria vaccine development (Patarroyo et al, 2012a , b , 2015a ). Modified HABPs (mHABPs) had been developed against highly-virulent P. falciparum Aotus -adapted FVO strain lethal intravenous challenge; they were derived from c onserved h igh a ctivity b inding p eptides (cHABPs) from proteins directly involved in the parasite's invasion of a host (hepatocytes, endothelial or red blood) cells (Patarroyo et al, 2017 ). This was the first demonstration that chemically-synthesized, vaccine-induced immune protection was associated with a particular 3D structure; (Patarroyo et al, 2015a ).…”

Plasmodium falciparum Blood Stage Antimalarial Vaccines: An Analysis of Ongoing Clinical Trials and New Perspectives Related to Synthetic Vaccines

“…The Pf AMA1-DiCo recombinant vaccine candidate is based on the AMA-1 protein concentrated at the Mrz apical pole which participates in their reorientation and RBC invasion (Remarque et al, 2008b; Kwenti et al, 2017). This protein is stored in the micronemes (Srinivasan et al, 2011); it is structurally formed by 614 aa, having a 83-kDa molecular weight (Patarroyo et al, 2017a). It is differentiated into two regions; the first has a 550-aa ectodomain divided into three domains (I, II, and III) located in the N-terminal extreme, and the second, a transmembrane, intracytoplasmic region located in the C-terminal extreme (Lim et al, 2014; Lumkul et al, 2018).…”

“…A vaccine targeting the erythrocyte stage capable of interrupting P. falciparum ’s asexual cycle could reduce parasitemia and morbidity by blocking invasion and the production of harmful by-products during parasite growth, which induces clinical symptomatology (Miura, 2016; Patarroyo et al, 2017a; Draper et al, 2018). Several blood-stage antigens have thus been identified as potential vaccine candidates; this led to FIDIC developing the first minimum subunit-based synthetic multi-epitope, multistage vaccine 30 years ago: synthetic P. falciparum vaccine 66 (SPf66).…”