Entry for:The Bioinformatics Peer Prize II
The Zika virus epidemic that started in Brazil in 2014-15 was marked by high incidence of neo-natal microcephaly and other neurolpgical disorders that has had no parallel in current human history. The reason why the virus which was apparently benign in Africa and Asia became highly pathogenic in Oceania and Latin America is still unclear, but it is vitally important to devise some means to stop the menace. We aid in this effort by devising a peptide vaccine against the Zika virus.
We needed to compare many ZIKV sequences for our work. Since some were partial sequences, we used our 2D graphical representation technique for nucleotide sequences (Nandy 2004) to pinpoint their location. For protein sequences we used our 20D method (Nandy et al 2009) to compare and determine segments that were best conserved. These segments were next compared with average solvent accessibility of the protein sequence to determine which segments were surface exposed. We also used 3D crystal structure to ensure the identified segments were indeed solvent accessible. The next step was to determine HLA binding efficiency for the target population (using IEDB) and identify those segments that were surface situated, well conserved and had good HLA binding efficiency to act as epitopes. Linear and conformational epitope possibilities were investigated. The segments that fulfilled all the criteria were then subjected to auto-immune threat tests and those that survived were proposed as peptide vaccine possibilities, subject of course to addition of adjuvants and other lab tests before trial phases.
Nandy, A., 1994. Curr. Sci. 66, 309– 314
Nandy, A., Ghosh, A., Nandy, P., 2009. In Silico Biol. 9, 77–87.
Our method yielded four peptide segments in the surface spanning envelope protein that met the above criteria. We used HLA DRB/DP/DQ alleles particular to the host population for MHCII efficiency determination and linear and conformational epitope analysis. We also used crystal structure of the envelope protein, 5IRE, to ensure solvent accessibility. The final peptides that met all the criteria were SPRAEATL, AGADTGTPHW and AAFTFTKVPA and constitute peptide regions that hold good potential as epitopes to act as starting points for laboratory work towards peptide vaccines against the Zika virus.
Our approach towards designing vaccine candidates against the Zika virus using the envelope surface protein has yielded good results. However, these are analysed from a truncated protein sequence and the peptides identified here are only a part of the full repertory of possible peptide targets, but could be taken as precursor to a multivalent peptide vaccine. We believe such bioinformatics approaches will assist in the process of eventual design of a rational peptide vaccine against the Zika virus which has emerged in epidemic form in Latin America since 2014-15 and has potential to spread and cause havoc across the world.
5. Future ideas/collaborators needed to further research?
The peptides identified here need to be tested in laboratory conditions to ensure they actually do yield reliable results. Such a step is crucial to development of a vaccine against the Zika virus. However, such experimental verification is also necessary to lend support to this approach for rational design of peptide vaccines. Given the high incidence and frequency of new viruses and viral epidemics, it is necessary to develop and lay down ground rules for developing preventives against future viruses. The current approach constitutes one rational strategy towards such development and therefore should be considered as a harbinger for such approaches, eliciting further research and development of the techniques for more efficient and faster identification of possible vaccine candidates.
Basak, S.C., Nandy, A., 2016 Curr. Comput.-Aided Drug Des. 12 (1), 2–4.
Nandy, A., Basak, S.C., 2016 SOJ Vacc. 1 (1), 3.
Nandy, A., Basak, S.C., 2017 J Mol Pathol Epidemiol. 2: S1.