In Sub-Saharan Africa, the malaria vaccine RTS,S/AS01 will commence in 2019 with a pilot immunization trial. RTS,S/AS01 Phase III studies showed a significant variability among studied locations of 28.3 percent (children 5–17 months) and 18.3 percent (children 6–12 weeks). The study suggested that RTS,S vaccination and variability across the locations are relatively low because of the lack of T-cell epitopes in the vaccine antigen, HLA distribution among the population and/or the immune escape mechanism owing to “immune camouflage.” Researchers have utilized immunoinformatics techniques to test these possibilities in order to compare the T helper epitopes of RTS (RadioTMS),S vaccine anti-substantive products with variations of Plasmodium falciparum circumsporozoite protein (CSP). Inverse associations were found with HLA-DRB1 allele prevalence in Malawi, suggesting that there might be an immunological escape from a particular HLA-DRB1 allele. In addition, the low-frequency HLA-DRB1 alleles in the population of the T-cell epitopes in the CSP in Malawi.

Furthermore, TCR-facing residues that were highly conserved among CSP variations in Malawi were also highly conserved in the human proteome, presumably decreasing T-cell assistance through tolerance. The CSP component of the RTS,S vaccine was similarly shown to have a low degree of T-cell epitope similarity to circulating variations. These findings show that low T-cell epitope richness, decreased presentation of T-cell epitopes by ubiquitous HLA-DRB1, a high propensity for human-cross-reactivity, and inadequate conservation with the CSP of circulating malaria strains may all have an influence on RTS,S vaccine efficacy.