A Potential Malaria Vaccine Candidate Identified Using an Insilico Approach
Keywords:
Malaria, Plasmodium falciparum parasite, vaccine candidate, hypothetical proteins.Abstract
The search for an effective malaria vaccine has yielded no success yet. Unfortunately, resistance to post-infection treatments is on the increase hence the need to develop an efficient vaccine. The aim of many reverse vaccinology studies is to identify novel proteins found exposed on the surface. Many malaria vaccine candidates can be effective tools against malaria but gross allelic polymorphism is a major hinderance which could be overcome by using highly conserved proteins. Also peptide based vaccines can be of great importance in fighting malaria however this is limited by HLA restriction which can be maneuvered by using promiscuous peptides. In the current work, our objective was to computationally identify conserved hypothetical, antigenic, surface proteins in pathogenic plasmodium falciparum parasite. So in this study, we employed an in silico approach to screen the proteins on the basis of surface localization, non-homology with host proteome, and MHC class I and II binding promiscuity. The analyses reported XP_001351004.1 an uncharacterized protein as a novel vaccine candidate. Generation of the 3D model of the protein was done using RaptorX server. Furthermore, the B cell and T cell epitopes were also predicted. B cell epitopes were predicted using ABCpred and Kolanskar and Tongaonkar antigenicity method while Tcell epitopes were predicted using CTLpred.
Five peptides were selected based on their hydrophobicity. Results from this study could be extended to in-vivo and in-vitro experiments for future vaccine development.
References
[ 1] Lopez, A.D., et al., Measuring the Global Burden of Disease and Risk Factors, 1990-2001, in Global Burden of Disease and Risk Factors, A.D. Lopez, et al., Editors. 2006: Washington (DC).
[2 ] Murray, C.J., et al., Global, regional, and national incidence and mortality for HIV, tuberculosis, and malaria during 1990-2013: a systematic analysis for the Global Burden of Disease Study 2013. Lancet, 2014. 384(9947): p. 1005-70.
[ 3] Organization, W.H., World malaria report 2014. 2014. Avarilable: http://www. who. int/malaria/publications/world_malaria_report_2014/en/. Accessed, 2015. 24.
[4 ] Beare, N.A., et al., Malarial retinopathy: a newly established diagnostic sign in severe malaria. Am J Trop Med Hyg, 2006. 75(5): p. 790-7.
[ 5] Titlic, M., Z. Josipovic-Jelic, and A. Punda, [Headache caused by pesticides--a review of the literature]. Acta Med Croatica, 2008. 62(2): p. 233-6.
[ 6] Banerjee, B.D., The influence of various factors on immune toxicity assessment of pesticide chemicals. Toxicol Lett, 1999. 107(1-3): p. 21-31.
[ 7] Van Maele-Fabry, G., et al., Residential exposure to pesticides and childhood leukaemia: a systematic review and meta-analysis. Environ Int, 2011. 37(1): p. 280-91.
[ 8] Hill, A.V., Vaccines against malaria. Philos Trans R Soc Lond B Biol Sci, 2011. 366(1579): p. 2806-14
[ 9] Draper, S.J., et al., Recent advances in recombinant protein-based malaria vaccines. Vaccine, 2015. 33(52): p. 7433-43.
[ 10] Sheehy, S.H., et al., ChAd63-MVA-vectored blood-stage malaria vaccines targeting MSP1 and AMA1: assessment of efficacy against mosquito bite challenge in humans. Mol Ther, 2012. 20(12): p. 2355-68.
[ 11] Ouattara, A., et al., Lack of allele-specific efficacy of a bivalent AMA1 malaria vaccine. Malar J, 2010. 9: p. 175.
[ 12]Efficacy and safety of RTS,S/AS01 malaria vaccine with or without a booster dose in infants and children in Africa: final results of a phase 3, individually randomised, controlled trial. The Lancet. 386(9988): p. 31-45.
[ 13] Olotu, A., et al., Efficacy of RTS,S/AS01E malaria vaccine and exploratory analysis on anti-circumsporozoite antibody titres and protection in children aged 5–17 months in Kenya and Tanzania: a randomised controlled trial. The Lancet Infectious Diseases, 2011. 11(2): p. 102-109.
[14 ] Marshall, V.M., et al., Diversity of the vaccine candidate AMA-1 of Plasmodium falciparum. Molecular and Biochemical Parasitology, 1996. 77(1): p. 109-113.
[ 15] Gardner, M.J., et al., Genome sequence of the human malaria parasite Plasmodium falciparum. Nature, 2002. 419(6906): p. 498-511
[ 16] Y, G.M., Conserved ‘Hypothetical’ Proteins: New Hints and New Puzzles. International Journal of Genomics, 2001. 2(1): p. 14-18.
[ 17] Galperin, M.Y. and E.V. Koonin, ‘Conserved hypothetical’ proteins: prioritization of targets for experimental study. Nucleic Acids Research, 2004. 32(18): p. 5452-5463.
[ 18] Loewenstein Y, Raimondo D, Redfern OC, Watson J, et al. (2009). Protein function annotation by homology-based inference. Genome Biol. 10: 207
[ 19] Desler C, Suravajhala P, Sanderhoff M, Rasmussen M, et al.(2009). In Silico screening for functional candidates amongst hypothetical proteins. BMC Bioinformatics10: 289
[ 20] Kumar K, Prakash A, Tasleem M, Islam A, Ahmad F, Hassan MI. Functional annotation of putative hypothetical proteins from Candida dubliniensis. Gene. 2014;543:93–100. doi: 10.1016/j.gene.2014.03.060.
[21 ] G. Lubec, L. Afjehi-Sadat, J.W. Yang, J.P. John.Searching for hypothetical proteins: theory and practice based upon original data and literature Prog. Neurobiol., 77 (2005), pp. 90-127
[ 22] Tomar N, De RK (2010) Immunoinformatics: an integrated scenario.Immunology 131:153–168
[ 23] Rappuoli, R., Reverse vaccinology. Current Opinion in Microbiology, 2000. 3(5): p. 445-450
[24 ] Plebanski, M., et al., Malaria vaccines: into a mirror, darkly? Trends Parasitol, 2008. 24(12): p. 532-6.
[ 25] Petersen, T.N., et al., SignalP 4.0: discriminating signal peptides from transmembrane regions. Nat Methods, 2011. 8(10): p. 785-6.
[ 26] Krogh, A., et al., Predicting transmembrane protein topology with a hidden Markov model: application to complete genomes. J Mol Biol, 2001. 305(3): p. 567-80.
[ 27] Horton, P., et al., WoLF PSORT: protein localization predictor. Nucleic Acids Res, 2007. 35(Web Server issue): p. W585-7.
[ 28] Yu CS, Chen YC, Lu CH, Hwang JK (2006) Prediction of protein subcellular localization. Proteins: Structure, Function and
Bioinformatics 64:643–651
[29 ] Altschul, S.F., et al., Gapped BLAST and PSI-BLAST: a new generation of protein database search programs. Nucleic Acids Research, 1997. 25(17): p. 3389-3402.
[ 30] Chawley P, Samal HB, Prava J, Suar M, Mahapatra RK (2014) Comparative genomics study for identification of drug and vaccine targets in Vibrio cholerae: MurA ligase as a case study. Genomics 103:83–93
[ 31] Singh H, Raghava GPS (2003) ProPred1: prediction of promiscuous MHC class-I binding sites. Bioinformatics 19:1009–1014
[ 32] Chen J, Liu H, Yang J, Chou KC (2007) Prediction of linear B-cell epitopes using amino acid pair antigenicity scale. Amino Acids 33(3):423–428
[ 33] Kolaskar, A.S. and P.C. Tongaonkar, A semi-empirical method for prediction of antigenic determinants on protein antigens. FEBS Letters, 1990. 276(1–2): p. 172-174.
[ 34] Källberg M, Margaryan G,Wang S, Ma J, Xu J (2014) RaptorX server: aresource for template-based protein structure modeling. Methods Mol Biol 1137:17–27.
[ 35] Ariel, N., et al., Search for potential vaccine candidate open reading frames in the Bacillus anthracis virulence plasmid pXO1: in silico and in vitro screening. Infection and immunity, 2002. 70(12): p. 6817-6827.
[ 36] Nielsen, H., et al., Identification of prokaryotic and eukaryotic signal peptides and prediction of their cleavage sites. Protein Engineering, Design and Selection, 1997. 10(1): p. 1-6.
[ 37] Kindt TJ, Goldsby RA, Osborne BA (2007) B-cell generation, activation, and differentiation. Kuby immunology. WH Freeman and Company, New York, pp 271–301
[ 38]Vetrivel, U., Subramanian, G., Fau-Dorairaj, S., Dorairaj, S., 2005. A novel in silico approach to identify potential therapeutic targets in human bacterial pathogens (1877-6566 (Electronic)) doi: D - NLM: PMC3238024 OTO - NOTNLM
[39 ] Klein J, Horejsi V. Immunology. Oxford, Blackwell Science; 1997.
[ 40] Dengjel J, Schoor O, Fischer R, Reich M, Kraus M, et al. Autophagy promotes MHC class II presentation of peptides from intracellular source proteins. Proc Nat Acad Sci USA. 2005;102:7922–7927. doi: 10.1073/pnas.0501190102.
[ 41] Saha S and Raghava GP: Prediction of continuous B cell epitopes in an antigen using recurrent neural network. Proteins 65: 40 48, 2006.
[ 42] .Parker JM, Guo D and Hodges RS: New hydrophilicity scale derived from high performance liquid chromatography peptide retention data: Correlation of predicted surface residues with antigenicity and X ray derived accessible sites. Biochemistry 25: 5425 5432, 1986.
[ 43] Karplus PA and Schulz GE: Prediction of chain flexibility in proteins. Naturwissenschaften 72: 212 213, 1985.
[ 44] Emini EA, Hughes JV, Perlow DS and Boger J: Induction of hepatitis A virus neutralizing antibody by a virus specific synthetic peptide. J Virol 55: 836 839, 1985
[ 45] Lesley, S. A., P. Kuhn, A. Godzik, A. M. Deacon, I. Mathews, A. Kreusch, G. Spraggon, H. E. Klock, D. McMullan, T. Shin, J. Vincent, A. Robb, L. S. Brinen, M. D. Miller, T. M. McPhillips, M. A. Miller, D. Scheibe, J. M. Canaves, C. Guda, L. Jaroszewski, T. L. Selby, M.-A. Elslinger, S. S. Taylor, K. O. Hodgson, I. A. Wilson, P. G. Schultz, and R. A. Stevens. 2002. Structural genomics of the Thermotoga maritime proteome implemented in a high-throughput structure determination pipeline. Proc. Natl. Acad. Sci. USA 99:11664-11669.
[2 ] Murray, C.J., et al., Global, regional, and national incidence and mortality for HIV, tuberculosis, and malaria during 1990-2013: a systematic analysis for the Global Burden of Disease Study 2013. Lancet, 2014. 384(9947): p. 1005-70.
[ 3] Organization, W.H., World malaria report 2014. 2014. Avarilable: http://www. who. int/malaria/publications/world_malaria_report_2014/en/. Accessed, 2015. 24.
[4 ] Beare, N.A., et al., Malarial retinopathy: a newly established diagnostic sign in severe malaria. Am J Trop Med Hyg, 2006. 75(5): p. 790-7.
[ 5] Titlic, M., Z. Josipovic-Jelic, and A. Punda, [Headache caused by pesticides--a review of the literature]. Acta Med Croatica, 2008. 62(2): p. 233-6.
[ 6] Banerjee, B.D., The influence of various factors on immune toxicity assessment of pesticide chemicals. Toxicol Lett, 1999. 107(1-3): p. 21-31.
[ 7] Van Maele-Fabry, G., et al., Residential exposure to pesticides and childhood leukaemia: a systematic review and meta-analysis. Environ Int, 2011. 37(1): p. 280-91.
[ 8] Hill, A.V., Vaccines against malaria. Philos Trans R Soc Lond B Biol Sci, 2011. 366(1579): p. 2806-14
[ 9] Draper, S.J., et al., Recent advances in recombinant protein-based malaria vaccines. Vaccine, 2015. 33(52): p. 7433-43.
[ 10] Sheehy, S.H., et al., ChAd63-MVA-vectored blood-stage malaria vaccines targeting MSP1 and AMA1: assessment of efficacy against mosquito bite challenge in humans. Mol Ther, 2012. 20(12): p. 2355-68.
[ 11] Ouattara, A., et al., Lack of allele-specific efficacy of a bivalent AMA1 malaria vaccine. Malar J, 2010. 9: p. 175.
[ 12]Efficacy and safety of RTS,S/AS01 malaria vaccine with or without a booster dose in infants and children in Africa: final results of a phase 3, individually randomised, controlled trial. The Lancet. 386(9988): p. 31-45.
[ 13] Olotu, A., et al., Efficacy of RTS,S/AS01E malaria vaccine and exploratory analysis on anti-circumsporozoite antibody titres and protection in children aged 5–17 months in Kenya and Tanzania: a randomised controlled trial. The Lancet Infectious Diseases, 2011. 11(2): p. 102-109.
[14 ] Marshall, V.M., et al., Diversity of the vaccine candidate AMA-1 of Plasmodium falciparum. Molecular and Biochemical Parasitology, 1996. 77(1): p. 109-113.
[ 15] Gardner, M.J., et al., Genome sequence of the human malaria parasite Plasmodium falciparum. Nature, 2002. 419(6906): p. 498-511
[ 16] Y, G.M., Conserved ‘Hypothetical’ Proteins: New Hints and New Puzzles. International Journal of Genomics, 2001. 2(1): p. 14-18.
[ 17] Galperin, M.Y. and E.V. Koonin, ‘Conserved hypothetical’ proteins: prioritization of targets for experimental study. Nucleic Acids Research, 2004. 32(18): p. 5452-5463.
[ 18] Loewenstein Y, Raimondo D, Redfern OC, Watson J, et al. (2009). Protein function annotation by homology-based inference. Genome Biol. 10: 207
[ 19] Desler C, Suravajhala P, Sanderhoff M, Rasmussen M, et al.(2009). In Silico screening for functional candidates amongst hypothetical proteins. BMC Bioinformatics10: 289
[ 20] Kumar K, Prakash A, Tasleem M, Islam A, Ahmad F, Hassan MI. Functional annotation of putative hypothetical proteins from Candida dubliniensis. Gene. 2014;543:93–100. doi: 10.1016/j.gene.2014.03.060.
[21 ] G. Lubec, L. Afjehi-Sadat, J.W. Yang, J.P. John.Searching for hypothetical proteins: theory and practice based upon original data and literature Prog. Neurobiol., 77 (2005), pp. 90-127
[ 22] Tomar N, De RK (2010) Immunoinformatics: an integrated scenario.Immunology 131:153–168
[ 23] Rappuoli, R., Reverse vaccinology. Current Opinion in Microbiology, 2000. 3(5): p. 445-450
[24 ] Plebanski, M., et al., Malaria vaccines: into a mirror, darkly? Trends Parasitol, 2008. 24(12): p. 532-6.
[ 25] Petersen, T.N., et al., SignalP 4.0: discriminating signal peptides from transmembrane regions. Nat Methods, 2011. 8(10): p. 785-6.
[ 26] Krogh, A., et al., Predicting transmembrane protein topology with a hidden Markov model: application to complete genomes. J Mol Biol, 2001. 305(3): p. 567-80.
[ 27] Horton, P., et al., WoLF PSORT: protein localization predictor. Nucleic Acids Res, 2007. 35(Web Server issue): p. W585-7.
[ 28] Yu CS, Chen YC, Lu CH, Hwang JK (2006) Prediction of protein subcellular localization. Proteins: Structure, Function and
Bioinformatics 64:643–651
[29 ] Altschul, S.F., et al., Gapped BLAST and PSI-BLAST: a new generation of protein database search programs. Nucleic Acids Research, 1997. 25(17): p. 3389-3402.
[ 30] Chawley P, Samal HB, Prava J, Suar M, Mahapatra RK (2014) Comparative genomics study for identification of drug and vaccine targets in Vibrio cholerae: MurA ligase as a case study. Genomics 103:83–93
[ 31] Singh H, Raghava GPS (2003) ProPred1: prediction of promiscuous MHC class-I binding sites. Bioinformatics 19:1009–1014
[ 32] Chen J, Liu H, Yang J, Chou KC (2007) Prediction of linear B-cell epitopes using amino acid pair antigenicity scale. Amino Acids 33(3):423–428
[ 33] Kolaskar, A.S. and P.C. Tongaonkar, A semi-empirical method for prediction of antigenic determinants on protein antigens. FEBS Letters, 1990. 276(1–2): p. 172-174.
[ 34] Källberg M, Margaryan G,Wang S, Ma J, Xu J (2014) RaptorX server: aresource for template-based protein structure modeling. Methods Mol Biol 1137:17–27.
[ 35] Ariel, N., et al., Search for potential vaccine candidate open reading frames in the Bacillus anthracis virulence plasmid pXO1: in silico and in vitro screening. Infection and immunity, 2002. 70(12): p. 6817-6827.
[ 36] Nielsen, H., et al., Identification of prokaryotic and eukaryotic signal peptides and prediction of their cleavage sites. Protein Engineering, Design and Selection, 1997. 10(1): p. 1-6.
[ 37] Kindt TJ, Goldsby RA, Osborne BA (2007) B-cell generation, activation, and differentiation. Kuby immunology. WH Freeman and Company, New York, pp 271–301
[ 38]Vetrivel, U., Subramanian, G., Fau-Dorairaj, S., Dorairaj, S., 2005. A novel in silico approach to identify potential therapeutic targets in human bacterial pathogens (1877-6566 (Electronic)) doi: D - NLM: PMC3238024 OTO - NOTNLM
[39 ] Klein J, Horejsi V. Immunology. Oxford, Blackwell Science; 1997.
[ 40] Dengjel J, Schoor O, Fischer R, Reich M, Kraus M, et al. Autophagy promotes MHC class II presentation of peptides from intracellular source proteins. Proc Nat Acad Sci USA. 2005;102:7922–7927. doi: 10.1073/pnas.0501190102.
[ 41] Saha S and Raghava GP: Prediction of continuous B cell epitopes in an antigen using recurrent neural network. Proteins 65: 40 48, 2006.
[ 42] .Parker JM, Guo D and Hodges RS: New hydrophilicity scale derived from high performance liquid chromatography peptide retention data: Correlation of predicted surface residues with antigenicity and X ray derived accessible sites. Biochemistry 25: 5425 5432, 1986.
[ 43] Karplus PA and Schulz GE: Prediction of chain flexibility in proteins. Naturwissenschaften 72: 212 213, 1985.
[ 44] Emini EA, Hughes JV, Perlow DS and Boger J: Induction of hepatitis A virus neutralizing antibody by a virus specific synthetic peptide. J Virol 55: 836 839, 1985
[ 45] Lesley, S. A., P. Kuhn, A. Godzik, A. M. Deacon, I. Mathews, A. Kreusch, G. Spraggon, H. E. Klock, D. McMullan, T. Shin, J. Vincent, A. Robb, L. S. Brinen, M. D. Miller, T. M. McPhillips, M. A. Miller, D. Scheibe, J. M. Canaves, C. Guda, L. Jaroszewski, T. L. Selby, M.-A. Elslinger, S. S. Taylor, K. O. Hodgson, I. A. Wilson, P. G. Schultz, and R. A. Stevens. 2002. Structural genomics of the Thermotoga maritime proteome implemented in a high-throughput structure determination pipeline. Proc. Natl. Acad. Sci. USA 99:11664-11669.
Downloads
Published
2018-10-21
How to Cite
Aguttu, C., Mukisa, A., Okech, B. A., & W. Lubega, G. (2018). A Potential Malaria Vaccine Candidate Identified Using an Insilico Approach. American Scientific Research Journal for Engineering, Technology, and Sciences, 48(1), 1–13. Retrieved from https://asrjetsjournal.org/index.php/American_Scientific_Journal/article/view/4040
Issue
Section
Articles
License
Authors who submit papers with this journal agree to the following terms.
