Computational design of ancestral and consensus sequence of apical membrane antigen 1 (AMA1) of Plasmodium spp
Abstract
Background: It is important to design a malaria vaccine targeting all human malaria parasites as well as non-human primate parasites to eradicate malaria and prevent zoonotic malaria. Apical membrane antigen 1 (AMA1) protein is shared by human-infecting Plasmodium species. Ancestral sequence reconstruction (ASR) and consensus sequence construction on AMA1 might be able to overcome the antigenic distinction between those species.
Objective: We aimed to computationally design the ancestral and consensus sequence of Plasmodium AMA1 protein and analyze the sequences for its putative immunogenicity.
Methods: We utilized bioinformatics software to computationally design ancestral and consensus sequences of AMA1 protein. AMA1 protein sequences of human-infecting Plasmodium and non-human primate Plasmodium were retrieved from PlasmoDB. ASR was designed using MEGA X while consensus was inferred using UGENE. Phylogenetic tree consisting of existing Plasmodium sequences and the ancestral sequence was constructed using IQTREE webserver and visualized with FigTree.
Results: Phylogenetic analysis showed that Plasmodium spp. were divided into 2 major groups, P. falciparum (Clade F) and non-falciparum (Clade NF) thus three ancestral and consensus sequences were designed based on each clade and both clades at once. Reconstructed ancestral sequences were located as sister branch for naturally occurring strains. On the contrary, consensus sequences are located within the branch of corresponding naturally occurring strains. Sequence analysis showed the presence of CD8+ T cell epitope in all computationally-designed sequences.
Conclusion: Ancestral and consensus AMA1 sequences are potential for further studies as a malaria vaccine candidate.
References
Vittor AY, Pan W, Gilman RH, Tielsch J, Glass G, Shields T, et al. Linking deforestation to malaria in the amazon: Characterization of the breeding habitat of the principal malaria vector, Anopheles darlingi. Am J Trop Med Hyg. 2013;10(1):54-6.
World Health Organization. World Malaria Report 2018 [Internet]. 2018. 1-210 p. Available from: https://www.who.int/malaria/publications/world-malaria-report-2018/en/
World Health Organization. Artemisinin resistance and artemisinin-based combination therapy efficacy [Internet]. World Health Organization. 2018. Available from: https://apps.who.int/iris/bitstream/handle/10665/274362/WHO-CDS-GMP-2018.18-eng.pdf?sequence=1&isAllowed=y
Noedl H, Se Y, Schaecher K, Smith BL, Socheat D, Fukuda MM. Evidence of artemisinin-resistant malaria in Western Cambodia. N Engl J Med. 2008;359(24):2619-20. https://doi.org/10.1056/NEJMc0805011
Amato R, Pearson RD, Almagro-Garcia J, Amaratunga C, Lim P, Suon S, et al. Origins of the current outbreak of multidrug-resistant malaria in southeast Asia: a retrospective genetic study. Lancet Infect Dis. 2018;18(3):337-45. https://doi.org/10.1016/S1473-3099(18)30068-9
Millar SB, Cox-Singh J. Human infections with Plasmodium knowlesi-zoonotic malaria. Clin Microbiol Infect. 2015;21(7):640-8. https://doi.org/10.1016/j.cmi.2015.03.017
Setiadi W, Sudoyo H, Trimarsanto H, Sihite BA, Saragih RJ, Juliawaty R, et al. A zoonotic human infection with simian malaria, Plasmodium knowlesi, in Central Kalimantan, Indonesia. Malar J. 2016;15(1):1-6. https://doi.org/10.1186/s12936-016-1272-z
Ramasamy R. Zoonotic malaria - global overview and research and policy needs. Front Public Heal. 2014;2(AUG):1-7. https://doi.org/10.3389/fpubh.2014.00123
Anstey NM, Grigg MJ. Zoonotic malaria: The better you look, the more you find. J Infect Dis. 2019;219(5):679-81. https://doi.org/10.1093/infdis/jiy520
Straub K, Merkl R. Ancestral sequence reconstruction as a tool for the elucidation of a stepwise evolutionary adaptation. In: Cycle. 2019:171-82. https://doi.org/10.1007/978-1-4939-8736-8_9
Sternke M, Tripp KW, Barrick D. Consensus sequence design as a general strategy to create hyperstable, biologically active proteins. Proc Natl Acad Sci U S A. 2019;166(23):11275-84. https://doi.org/10.1073/pnas.1816707116
Doria-Rose NA, Learn GH, Rodrigo AG, Nickle DC, Mahalanabis M, Hensel MT, et al. Human immunodeficiency virus type 1 subtype B ancestral envelope protein is functional and elicits neutralizing antibodies in rabbits similar to those elicited by a circulating subtype B envelope. J Virol. 2005;79(17):11214-24. https://doi.org/10.1128/JVI.79.17.11214-11224.2005
Ross HA, Nickle DC, Liu Y, Heath L, Jensen MA, Rodrigo AG, et al. Sources of variation in ancestral sequence reconstruction for HIV-1 envelope genes. Evol Bioinforma. 2006;2:117693430600200. https://doi.org/10.1177/117693430600200027
Kothe DL, Li Y, Decker JM, Bibollet-Ruche F, Zammit KP, Salazar MG, et al. Ancestral and consensus envelope immunogens for HIV-1 subtype C. Virology. 2006;352(2):438-49. https://doi.org/10.1016/j.virol.2006.05.011
Nurdiansyah R, Ramanto KN, Jessica P. Investigating the characteristics and evolution of apical membrane antigen 1 (AMA1) of Plasmodium sp. using phylogenetic approach in searching for drug candidate. In Jakarta: International Conference on Biotechnology and Life Sciences; 2019. https://doi.org/10.18502/kls.v5i2.6440
Jahangiri F, Jalallou N, Ebrahimi M. Analysis of apical membrane antigen (AMA)-1 characteristics using bioinformatics tools in order to vaccine design against Plasmodium vivax. Infect Genet Evol. 2019;71(March):224-31. https://doi.org/10.1016/j.meegid.2019.04.001
Coley AM, Parisi K, Masciantonio R, Hoeck J, Casey JL, Murphy VJ, et al. The most polymorphic residue on Plasmodium falciparum apical membrane antigen 1 determines binding of an invasion-inhibitory antibody. Infect Immun. 2006;74(5):2628-36. https://doi.org/10.1128/IAI.74.5.2628-2636.2006
Mitchell GH, Thomas AW, Margos G, Dluzewski AR, Bannister LH. Apical membrane antigen 1, a major malaria vaccine candidate, mediates the close attachment of invasive merozoites to host red blood cells. Infect Immun. 2004;72(1):154-8. https://doi.org/10.1128/IAI.72.1.154-158.2004
Bryan D, Silva N, Rigsby P, Dougall T, Corran P, Bowyer PW, et al. The establishment of a WHO Reference Reagent for anti-malaria (Plasmodium falciparum) human serum. Malar J. 2017;16(1):1-10. https://doi.org/10.1186/s12936-017-1958-x
Drew DR, Sanders PR, Weiss G, Gilson PR, Crabb BS, Beeson JG. Functional conservation of the AMA1 host-cell invasion ligand between P. falciparum and P. vivax: A novel platform to accelerate vaccine and drug development. J Infect Dis. 2018;217(3):498-503. https://doi.org/10.1093/infdis/jix583
Triglia T, Healer J, Caruana SR, Hodder AN, Anders RF, Crabb BS, et al. Apical membrane antigen 1 plays a central role in erythrocyte invasion by Plasmodium species. Mol Microbiol. 2000;38(4):706-18. https://doi.org/10.1046/j.1365-2958.2000.02175.x
Doumbo OK, Niaré K, Healy SA, Sagara I, Duffy PE. Malaria transmission-blocking vaccines: Present status and future perspectives. In: Towards malaria elimination - A Leap Forward. InTech. 2018:364-84. https://doi.org/10.5772/intechopen.77241
Heide J, Vaughan KC, Sette A, Jacobs T, Zur Wiesch JS. Comprehensive review of human plasmodium falciparum-specific CD8+ T cell epitopes. Front Immunol. 2019;10(MAR):1-23. https://doi.org/10.3389/fimmu.2019.00397
Drew DR, Hodder AN, Wilson DW, Foley M, Mueller I, Siba PM, et al. Defining the antigenic diversity of plasmodium falciparum apical membrane antigen 1 and the requirements for a multi-allele vaccine against malaria. PLoS One. 2012;7(12). https://doi.org/10.1371/journal.pone.0051023
Takala SL, Coulibaly D, Thera M a, Batchelor AH, Cummings MP, Escalante A a, et al. Extreme polymorphism in a vaccine antigen and risk of clinical malaria: Implications for vaccine development. Sci transl med. 2009;1(2):2ra5-2ra5. https://doi.org/10.1126/scitranslmed.3000257
Hall BG. Building phylogenetic trees from molecular data with MEGA. Mol Biol Evol. 2013;30(5):1229-35. https://doi.org/10.1093/molbev/mst012
Edgar RC. MUSCLE: Multiple sequence alignment with high accuracy and high throughput. Nucleic Acids Res. 2004;32(5):1792-7. https://doi.org/10.1093/nar/gkh340
Trifinopoulos J, Nguyen LT, von Haeseler A, Minh BQ. W-IQ-TREE: a fast online phylogenetic tool for maximum likelihood analysis. Nucleic Acids Res. 2016;44(W1):W232-5. https://doi.org/10.1093/nar/gkw256
Kumar S, Stecher G, Li M, Knyaz C, Tamura K. MEGA X: Molecular evolutionary genetics analysis across computing platforms. Mol Biol Evol. 2018;35(6):1547-9. https://doi.org/10.1093/molbev/msy096
Okonechnikov K, Golosova O, Fursov M, Varlamov A, Vaskin Y, Efremov I, et al. Unipro UGENE: A unified bioinformatics toolkit. Bioinformatics. 2012;28(8):1166-7. https://doi.org/10.1093/bioinformatics/bts091
Doytchinova IA, Flower DR. Bioinformatic approach for identifying parasite and fungal candidate subunit vaccines. Open Vaccine J. 2010;3(1):22-6. https://doi.org/10.2174/1875035400801010022
Collins CR, Withers-Martinez C, Bentley GA, Batchelor AH, Thomas AW, Blackman MJ. Fine mapping of an epitope recognized by an invasion-inhibitory monoclonal antibody on the malaria vaccine candidate apical membrane antigen 1. J Biol Chem. 2007;282(10):7431-41. https://doi.org/10.1074/jbc.M610562200
Bueno LL, Lobo FP, Morais CG, Mourão LC, de Ávila RAM, Soares IS, et al. Identification of a highly antigenic linear b cell epitope within plasmodium vivax apical membrane antigen 1 (AMA-1). PLoS One. 2011;6(6). https://doi.org/10.1371/journal.pone.0021289
Galaway F, Yu R, Constantinou A, Prugnolle F, Wright GJ. Resurrection of the ancestral RH5 invasion ligand provides a molecular explanation for the origin of P. falciparum malaria in humans. PLoS Biol. 2019;17(10):e3000490. https://doi.org/10.1371/journal.pbio.3000490
Proietti C, Doolan DL. The case for a rational genome-based vaccine against malaria. Front Microbiol. 2015;5(DEC):1-19. https://doi.org/10.3389/fmicb.2014.00741
Conway DJ. Paths to a malaria vaccine illuminated by parasite genomics. Trends Genet. 2015;31(2):97-107 https://doi.org/10.1016/j.tig.2014.12.005
Villard V, Agak GW, Frank G, Jafarshad A, Servis C, Nébié I, et al. Rapid identification of malaria vaccine candidates based on α-helical coiled coil protein motif. PLoS One. 2007;2(7). https://doi.org/10.1371/journal.pone.0000645
Tham WH, Beeson JG, Rayner JC. Plasmodium vivax vaccine research - we've only just begun. Int J Parasitol. 2017;47(2-3):111-8. https://doi.org/10.1016/j.ijpara.2016.09.006
Ouattara A, Mu J, Takala-Harrison S, Saye R, Sagara I, Dicko A, et al. Lack of allele-specific efficacy of a bivalent AMA1 malaria vaccine. Malar J. 2010;9(1):1-13. https://doi.org/10.1186/1475-2875-9-175
Bejon P, White MT, Olotu A, Bojang K, Lusingu JPA, Salim N, et al. Efficacy of RTS,S malaria vaccines: Individual-participant pooled analysis of phase 2 data. Lancet Infect Dis. 2013;13(4):319-27. https://doi.org/10.1016/S1473-3099(13)70005-7
Crompton PD, Moebius J, Portugal S, Waisberg M, Hart G, Garver LS, et al. Malaria immunity in man and mosquito: Insights into unsolved mysteries of a deadly infectious disease. Annu Rev Immunol. 2014;32(1):157-87. https://doi.org/10.1146/annurev-immunol-032713-120220
Riglar DT, Richard D, Wilson DW, Boyle MJ, Dekiwadia C, Turnbull L, et al. Super-resolution dissection of coordinated events during malaria parasite invasion of the human erythrocyte. Cell Host Microbe. 2011;9(1):9-20. https://doi.org/10.1016/j.chom.2010.12.003
Schwenk R, Banania G, Epstein J, Kim Y, Peters B, Belmonte M, et al. Ex vivo tetramer staining and cell surface phenotyping for early activation markers CD38 and HLA-DR to enumerate and characterize malaria antigen-specific CD8+ T-cells induced in human volunteers immunized with a Plasmodium falciparum adenovirus-vectored. Malar J. 2013;12(1):1. https://doi.org/10.1186/1475-2875-12-376
Sedegah M, Kim Y, Peters B, McGrath S, Ganeshan H, Lejano J, et al. Identification and localization of minimal MHC-restricted CD8+ T cell epitopes within the Plasmodium falciparum AMA1 protein. Malar J. 2010;9(1):1-16. https://doi.org/10.1186/1475-2875-9-241
Remarque EJ, Faber BW, Kocken CHM, Thomas AW. Apical membrane antigen 1: A malaria vaccine candidate in review. Trends Parasitol. 2008;24(2):74-84. https://doi.org/10.1016/j.pt.2007.12.002
Copyright (c) 2019 Authors
This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.
