Background:
The prevailing public health threat posed by malaria, especially in developing countries, remains a serious concern despite the availability of preventive and control measures. While vaccination offers a powerful means of combating malaria, it has not been fully exploited due to previous unsuccessful attempts before the launch of the RTS,S vaccine. A major challenge in malaria vaccine development continues to be the identification of effective targets capable of eliciting robust immunity, given the complexity of the parasites’ life cycle. Leveraging on the breakthrough of the newly approved malaria vaccine, efforts to develop more effective prophylactic solutions continue with renewed determination.

Material and methods:
In this study, a standard structural bioinformatics pipeline was employed to design a multiepitope subunit vaccine against Plasmodium, particularly P. falciparum. Thirty subunit epitopes were mined from selected variant surface antigens of P. falciparum proteins expressed at different stages of its life cycle, based on their vaccine-likeness. These epitopes were conjugated with suitable adjuvants and linkers into a vaccine construct, which was then subjected to stringent downstream analyses.

Results:
Out of an initial pool of 133 epitopes, 30 vaccine-fit epitopes were selected, resulting in a final vaccine construct comprising 570 amino acid residues. This included 12 linear B-cells, 11 cytotoxic T-lymphocytes, and 7 helper T-lymphocyte epitopes, all with favorable predicted structural, antigenic, and physicochemical properties. The construct also demonstrated strong global population coverage (95.04%), robust molecular binding, and simulated immune responses.

Conclusions:
With the evolving “Omics” technologies through reverse vaccinology, discovering and designing promising vaccine candidates becomes easier without many challenging experimental rigors. This study highlights the potential of immunoinformatics-aided approaches in accelerating effective malaria vaccine development.