The use of HLA-1 structures in the design of a computer based liver stage malaria vaccine

Abstract

Malaria is the most prevalent parasitic infection on earth with at least 40% of the world`s population at risk of infection, annually. It is currently the leading cause of morbidity in Uganda with 90-95% of the total population at risk. 4% of the world`s malaria cases in 2017 occurred in Uganda and the scourge was named the country’s leading cause of mortality and morbidity among young children and pregnant women. 8-13 million episodes, 30-50% outpatient hospital visits, 35% hospital admissions 9-14% hospital deaths and a host of other deaths outside the hospital setting served as evidence to that declaration. These statistics make it urgent to defeat malaria in the whole world especially in Uganda. Malaria must be defeated through a vaccine for anyone to rest easy, as it has refuted many wonder therapies over the years. The liver stage, being the only stage at which HLA I presentation can be relied upon in the whole P. falciparum lifecycle in the human host is a good opportunity for anti-malarial vaccination. Subunit and whole protein vaccines have shown many failures as mentioned. Discussed are some factors to be considered when developing a putative epitope based vaccine using in silico methods with a target of increasing frequency of protective alleles against malaria such as HLA B*53:01. Malaria is playing the most selective pressure on the human genome among all other pathogens and results such as a wide range of alleles presenting plasmodium epitopes attest to this fact. What length of epitope each allele prefers and the reasons why are discussed? Discussed too are the preferred amino acids per position for each allele with the conclusion that the HLA-1 system is of considerably low specificity. However, hydropathy, size and several side chain characteristics tend to dictate whether the epitope binds, the orientation of the epitope in the grove and the extent of memory and immunogenicity as factors of binding strength and duration.