{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,15]],"date-time":"2026-10-15T16:42:55Z","timestamp":1792082575739,"version":"4.4.0"},"reference-count":69,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2022,1,7]],"date-time":"2022-01-07T00:00:00Z","timestamp":1641513600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Vet. Sci."],"abstract":"<jats:p>Parasites of the phylum Apicomplexa are the causative agents of important diseases such as malaria, toxoplasmosis or cryptosporidiosis in humans, and babesiosis and coccidiosis in animals. Whereas the first human recombinant vaccine against malaria has been approved and recently recommended for wide administration by the WHO, most other zoonotic parasitic diseases lack of appropriate immunoprophylaxis. Sequencing technologies, bioinformatics, and statistics, have opened the \u201comics\u201d era into apicomplexan parasites, which has led to the development of systems biology, a recent field that can significantly contribute to more rational design for new vaccines. The discovery of novel antigens by classical approaches is slow and limited to very few antigens identified and analyzed by each study. High throughput approaches based on the expansion of the \u201comics\u201d, mainly genomics and transcriptomics have facilitated the functional annotation of the genome for many of these parasites, improving significantly the understanding of the parasite biology, interactions with the host, as well as virulence and host immune response. Developments in genetic manipulation in apicomplexan parasites have also contributed to the discovery of new potential vaccine targets. The present minireview does a comprehensive summary of advances in \u201comics\u201d, CRISPR\/Cas9 technologies, and in systems biology approaches applied to apicomplexan parasites of economic and zoonotic importance, highlighting their potential of the holistic view in vaccine development.<\/jats:p>","DOI":"10.3389\/fvets.2021.800361","type":"journal-article","created":{"date-parts":[[2022,1,7]],"date-time":"2022-01-07T08:20:50Z","timestamp":1641543650000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":14,"title":["Next-Generation Technologies and Systems Biology for the Design of Novel Vaccines Against Apicomplexan Parasites"],"prefix":"10.3389","volume":"8","author":[{"given":"Mariela Luj\u00e1n","family":"Tomazic","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Virginia","family":"Marugan-Hernandez","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anabel Elisa","family":"Rodriguez","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2022,1,7]]},"reference":[{"key":"B1","first-page":"438","article-title":"Parasitic protozoa of farm animals and pets. Parasitic Protozoa of Farm Animals and Pets","author":"Florin-Christensen","year":"2018"},{"key":"B2","doi-asserted-by":"publisher","first-page":"1202","DOI":"10.1101\/gr.083386.108","article-title":"The origins of apicomplexan sequence innovation","volume":"7","author":"Wasmuth","year":"2009","journal-title":"Genome Res."},{"key":"B3","doi-asserted-by":"publisher","first-page":"6614","DOI":"10.1016\/j.vaccine.2011.06.110","article-title":"Protective effect against toxoplasmosis in mice induced by DNA immunization with gene encoding Toxoplasma gondii ROP18","volume":"29","author":"Yuan","year":"2011","journal-title":"Vaccine."},{"key":"B4","article-title":"An inquiry into the causes and effects of the variole vaccine, or cow-pox","author":"Jenner","year":"1798"},{"key":"B5","doi-asserted-by":"publisher","first-page":"283","DOI":"10.1136\/bmj.2.1076.283","article-title":"An Address on Vaccination in Relation to Chicken Cholera and Splenic Fever","volume":"2","author":"Pasteur","year":"1881","journal-title":"Br Med J"},{"key":"B6","first-page":"1471","article-title":"Tick fever. Notes on the inoculation of bulls as a preventive against tick fever at Rathdowney and Rosedale","author":"Pound","year":"1897","journal-title":"Queensl Agric J."},{"key":"B7","first-page":"1","article-title":"Texas fever. Experiments made by the Missouri experiment station and the Missouri state board of agriculture in cooperation with the Texas experiment station in immunizing northern breeding cattle against Texas fever for the southern trade Mo","volume":"48","author":"Connaway","year":"1899","journal-title":"Agric Exp Stn Bull."},{"key":"B8","doi-asserted-by":"publisher","first-page":"1099","DOI":"10.1016\/S0020-7519(98)00078-2","article-title":"Use of live oocyst vaccines in the control of avian coccidiosis: Experimental studies and field trials","volume":"28","author":"Danforth","year":"1998","journal-title":"Int J Parasitol."},{"key":"B9","doi-asserted-by":"publisher","first-page":"29","DOI":"10.1016\/0304-4017(94)90054-X","article-title":"review on vaccination against protozoa and arthropods of veterinary importance","volume":"55","author":"Barriga","year":"1994","journal-title":"Vet Parasitol."},{"key":"B10","article-title":"The World malaria report 2018","year":"2018"},{"key":"B11","doi-asserted-by":"publisher","first-page":"480","DOI":"10.1080\/21645515.2019.1669415","article-title":"RTS,S\/AS01 vaccine (MosquirixTM): an overview","volume":"3","author":"Laurens","year":"2020","journal-title":"Hum Vaccin Immunother."},{"key":"B12","unstructured":"First malaria vaccine receives positive scientific opinion from EMA Mosquirix to be used for vaccination of young children2015"},{"key":"B13","unstructured":"WHO recommends groundbreaking malaria vaccine for children at risk2021"},{"key":"B14","doi-asserted-by":"publisher","first-page":"95","DOI":"10.3923\/jbs.2014.95.109","article-title":"Trends and advances in vaccines against protozoan parasites of veterinary importance: A review","volume":"14","author":"Singh","year":"2014","journal-title":"J Biol Sci."},{"key":"B15","doi-asserted-by":"publisher","first-page":"358","DOI":"10.1016\/j.meegid.2017.10.009","article-title":"Recombinant anticoccidial vaccines - a cup half full?","volume":"55","author":"Blake","year":"2017","journal-title":"Infect Genet Evol."},{"key":"B16","doi-asserted-by":"publisher","first-page":"316","DOI":"10.1186\/s12864-016-2632-3","article-title":"Comparative genomics reveals Cyclospora cayetanensis possesses coccidia-like metabolism and invasion components but unique surface antigens","volume":"17","author":"Liu","year":"2016","journal-title":"BMC Genomics."},{"key":"B17","doi-asserted-by":"publisher","first-page":"189","DOI":"10.1016\/j.ijpara.2016.11.007","article-title":"The genome of the protozoan parasite Cystoisospora suis and a reverse vaccinology approach to identify vaccine candidates","volume":"47","author":"Palmieri","year":"2017","journal-title":"Int J Parasitol."},{"key":"B18","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1038\/s41598-017-04049-1","article-title":"Eimeria tenella protein trafficking: Differential regulation of secretion versus surface tethering during the life cycle","volume":"7","author":"Marugan-Hernandez","year":"2017","journal-title":"Sci Rep."},{"key":"B19","doi-asserted-by":"publisher","first-page":"477","DOI":"10.1038\/nature14651","article-title":"Genetic modification of the diarrhoeal pathogen Cryptosporidium parvum","volume":"523","author":"Vinayak","year":"2015","journal-title":"Nature."},{"key":"B20","doi-asserted-by":"publisher","DOI":"10.1042\/EBC20180003","article-title":"Systems biology primer: The basic methods and approaches","author":"Tavassoly","year":"2018","journal-title":"Essays Biochem."},{"key":"B21","doi-asserted-by":"publisher","first-page":"10a033308","DOI":"10.1101\/cshperspect.a033308","article-title":"Will systems biology deliver its promise and contribute to the development of new or improved vaccines?: What really constitutes the study of \u201csystems biology\u201d and how might such an approach facilitate vaccine design","volume":"1","author":"Germain","year":"2018","journal-title":"Cold Spring Harb Perspect Biol."},{"key":"B22","doi-asserted-by":"publisher","first-page":"a028894","DOI":"10.1101\/cshperspect.a028894","article-title":"Pulendran B. Will systems biology deliver its promise and contribute to the development of new or improved vaccines?: From data to understanding through systems biology","volume":"10","author":"Hagan","year":"2018","journal-title":"Cold Spring Harb Perspect Biol."},{"key":"B23","doi-asserted-by":"publisher","first-page":"646","DOI":"10.1038\/s41598-018-36671-y","article-title":"Gene target discovery with network analysis in Toxoplasma gondii","volume":"9","author":"Alonso","year":"2019","journal-title":"Sci Rep"},{"key":"B24","doi-asserted-by":"publisher","first-page":"5294","DOI":"10.1016\/j.vaccine.2015.03.072","article-title":"Systems vaccinology: Enabling rational vaccine design with systems biological approaches","volume":"33","author":"Hagan","year":"2015","journal-title":"Vaccine."},{"key":"B25","doi-asserted-by":"publisher","first-page":"498","DOI":"10.1038\/nature01097","article-title":"Genome sequence of the human malaria parasite Plasmodium falciparum","volume":"419","author":"Gardner","year":"2002","journal-title":"Nature."},{"key":"B26","doi-asserted-by":"publisher","first-page":"381","DOI":"10.1002\/wsbm.1311","article-title":"Systems analysis of host-parasite interactions","volume":"7","author":"Swann","year":"2015","journal-title":"Wiley Interdiscip Rev Syst Biol Med."},{"key":"B27","doi-asserted-by":"publisher","first-page":"1676","DOI":"10.1101\/gr.168955.113","article-title":"Genomic analysis of the causative agents of coccidiosis in domestic chickens","volume":"24","author":"Reid","year":"2014","journal-title":"Genome Res."},{"key":"B28","doi-asserted-by":"publisher","first-page":"e1001279","DOI":"10.1371\/journal.ppat.1001279","article-title":"Genetic mapping identifies novel highly protective antigens for an apicomplexan parasite","volume":"7","author":"Blake","year":"2011","journal-title":"PLoS Pathog."},{"key":"B29","doi-asserted-by":"publisher","first-page":"647","DOI":"10.1186\/1471-2164-13-647","article-title":"Transcriptome analysis reveals unique metabolic features in the Cryptosporidium parvum Oocysts associated with environmental survival and stresses","volume":"13","author":"Zhang","year":"2012","journal-title":"BMC Genomics."},{"key":"B30","doi-asserted-by":"publisher","first-page":"329","DOI":"10.1128\/EC.1.3.329-340.2002","article-title":"Toxoplasma gondii asexual development: Identification of developmentally regulated genes and distinct patterns of gene expression","volume":"1","author":"Cleary","year":"2002","journal-title":"Eukaryot Cell."},{"key":"B31","doi-asserted-by":"publisher","first-page":"4","DOI":"10.1016\/j.cbpa.2012.12.008","article-title":"Transcriptomics in the RNA-seq era","volume":"17","author":"McGettigan","year":"2013","journal-title":"Curr Opin Chem Biol"},{"key":"B32","doi-asserted-by":"publisher","first-page":"806","DOI":"10.1186\/1471-2164-15-806","article-title":"Dual transcriptional profiling of mice and Toxoplasma gondii during acute and chronic infection","volume":"15","author":"Pittman","year":"2014","journal-title":"BMC Genomics."},{"key":"B33","doi-asserted-by":"publisher","first-page":"653085","DOI":"10.3389\/fimmu.2021.653085","article-title":"Kinetics of the cellular and transcriptomic response to eimeria maxima in relatively resistant and susceptible chicken lines","volume":"2","author":"Bremner","year":"2021","journal-title":"Front Immunol."},{"key":"B34","doi-asserted-by":"publisher","first-page":"2618","DOI":"10.1002\/pmic.201400553","article-title":"A large-scale proteogenomics study of apicomplexan pathogens-Toxoplasma gondii and Neospora caninum","volume":"15","author":"Krishna","year":"2015","journal-title":"Proteomics"},{"key":"B35","doi-asserted-by":"publisher","first-page":"520","DOI":"10.1038\/nature01107","article-title":"A proteomic view of the Plasmodium falciparum life cycle","volume":"419","author":"Florens","year":"2002","journal-title":"Nature."},{"key":"B36","doi-asserted-by":"publisher","first-page":"537","DOI":"10.1038\/nature01111","article-title":"Analysis of the Plasmodium falciparum proteome by high-accuracy mass spedrometry","volume":"419","author":"Lasonder","year":"2002","journal-title":"Nature."},{"key":"B37","doi-asserted-by":"publisher","first-page":"346","DOI":"10.1074\/mcp.M600372-MCP200","article-title":"Proteomics analysis and protein expression during sporozoite excystation of Cryptosporidium parvum (Coccidia, Apicomplexa)","volume":"6","author":"Snelling","year":"2007","journal-title":"Mol Cell Proteomics."},{"key":"B38","doi-asserted-by":"publisher","first-page":"1398","DOI":"10.1002\/pmic.200700804","article-title":"Determining the protein repertoire of Cryptosporidium parvum sporozoites","volume":"8","author":"Sanderson","year":"2008","journal-title":"Proteomics."},{"key":"B39","doi-asserted-by":"publisher","first-page":"R116","DOI":"10.1186\/gb-2008-9-7-r116","article-title":"The proteome of Toxoplasma gondii: Integration with the genome provides novel insights into gene expression and annotation","volume":"9","author":"Xia","year":"2008","journal-title":"Genome Biol."},{"key":"B40","doi-asserted-by":"publisher","first-page":"34245","DOI":"10.1074\/jbc.M504158200","article-title":"Proteomic analysis of rhoptry organelles reveals many novel constituents for host-parasite interactions in Toxoplasma gondii","volume":"280","author":"Bradley","year":"2005","journal-title":"J Biol Chem."},{"key":"B41","doi-asserted-by":"publisher","first-page":"629","DOI":"10.1016\/j.jprot.2011.02.004","article-title":"Identification of novel rhoptry proteins in Neospora caninum by LC\/MS-MS analysis of subcellular fractions","volume":"74","author":"Marug\u00e1n-Hern\u00e1ndez","year":"2011","journal-title":"J Proteomics."},{"key":"B42","doi-asserted-by":"publisher","first-page":"2306","DOI":"10.1016\/j.jprot.2012.01.039","article-title":"Proteome expression changes among virulent and attenuated Neospora caninum isolates","volume":"75","author":"Regidor-Cerrillo","year":"2012","journal-title":"J Proteomics."},{"key":"B43","doi-asserted-by":"publisher","first-page":"97","DOI":"10.1017\/S0031182015001511","article-title":"Characterization of the Neospora caninum NcROP40 and NcROP2Fam-1 rhoptry proteins during the tachyzoite lytic cycle","volume":"143","author":"Pastor-Fern\u00e1ndez","year":"2015","journal-title":"Parasitology."},{"key":"B44","doi-asserted-by":"publisher","first-page":"683","DOI":"10.1038\/s42003-020-01384-4","article-title":"Multiplexed quantitative proteomics provides mechanistic cues for malaria severity and complexity","volume":"3","author":"Kumar","year":"2020","journal-title":"Commun Biol."},{"key":"B45","doi-asserted-by":"publisher","first-page":"13882","DOI":"10.1021\/bi7011993","article-title":"Lipidomic Analysis of Toxoplasma gondii Reveals Unusual Polar Lipids","volume":"46","author":"Welti","year":"2007","journal-title":"Biochemistry."},{"key":"B46","doi-asserted-by":"publisher","first-page":"1815","DOI":"10.1021\/jasms.0c00043","article-title":"Intracellular Parasites Toxoplasma gondii and Besnoitia besnoiti, Unveiled in Single Host Cells Using AP-SMALDI MS Imaging","volume":"31","author":"Kadesch","year":"2020","journal-title":"J Am Soc Mass Spectrom."},{"key":"B47","doi-asserted-by":"publisher","first-page":"409","DOI":"10.1016\/j.pt.2019.03.004","article-title":"CRISPR in parasitology: not exactly cut and dried!","volume":"35","author":"Bryant","year":"2019","journal-title":"Trends Parasitol."},{"key":"B48","doi-asserted-by":"publisher","first-page":"915","DOI":"10.1038\/nmeth.3063","article-title":"Efficient CRISPR-Cas9-mediated genome editing in Plasmodium falciparum","volume":"11","author":"Wagner","year":"2014","journal-title":"Nat Methods."},{"key":"B49","doi-asserted-by":"publisher","first-page":"819","DOI":"10.1038\/nbt.2925","article-title":"Genome editing in the human malaria parasite Plasmodium falciparum using the CRISPR-Cas9 system","volume":"32","author":"Ghorbal","year":"2014","journal-title":"Nat Biotechnol."},{"key":"B50","doi-asserted-by":"publisher","first-page":"170095","DOI":"10.1098\/rsos.170095","article-title":"Cas9 high-throughput genome editing toolkit for kinetoplastids","volume":"4","author":"Beneke","year":"2017","journal-title":"R Soc Open Sci."},{"key":"B51","doi-asserted-by":"publisher","first-page":"e01414","DOI":"10.1128\/mBio.01414-14","article-title":"Efficient editing of malaria parasite genome using the CRISPR\/Cas9 system","volume":"5","author":"Zhang","year":"2014","journal-title":"MBio."},{"key":"B52","doi-asserted-by":"publisher","first-page":"1423","DOI":"10.1016\/j.cell.2016.08.019","article-title":"A Genome-wide CRISPR screen in toxoplasma identifies essential apicomplexan genes","volume":"166","author":"Sidik","year":"2016","journal-title":"Cell"},{"key":"B53","doi-asserted-by":"publisher","first-page":"4","DOI":"10.1186\/s13567-020-00766-0","article-title":"Genetic modification of the protozoan Eimeria tenella using the CRISPR\/Cas9 system","volume":"51","author":"Tang","year":"2020","journal-title":"Vet Res."},{"key":"B54","doi-asserted-by":"crossref","first-page":"219","DOI":"10.1007\/978-1-4939-9748-0_13","article-title":"Genetic Manipulation of Cryptosporidium parvum with CRISPR\/Cas9","volume-title":"Cryptosporidium: Methods and Protocols","author":"Sateriale","year":"2020"},{"key":"B55","doi-asserted-by":"publisher","first-page":"3963","DOI":"10.1038\/s41467-019-11855-w","article-title":"A CRISPR platform for targeted in vivo screens identifies Toxoplasma gondii virulence factors in mice","volume":"10","author":"Young","year":"2019","journal-title":"Nat Commun."},{"key":"B56","doi-asserted-by":"publisher","first-page":"1104","DOI":"10.1074\/jbc.RA118.006072","article-title":"CRISPR\/Cas9 and glycomics tools for Toxoplasma glycobiology","volume":"294","author":"Gas-Pascual","year":"2019","journal-title":"J Biol Chem."},{"key":"B57","doi-asserted-by":"publisher","first-page":"5561","DOI":"10.1128\/IAI.00408-06","article-title":"Common and divergent immune response signaling pathways discovered in peripheral blood mononuclear cell gene expression patterns in presymptomatic and clinically apparent malaria","volume":"74","author":"Ockenhouse","year":"2006","journal-title":"Infect Immun."},{"key":"B58","doi-asserted-by":"publisher","first-page":"162639","DOI":"10.1155\/2015\/162639","article-title":"Human Gene Expression in Uncomplicated Plasmodium falciparum Malaria","volume":"2015","author":"Colborn","year":"2015","journal-title":"J Immunol Res."},{"key":"B59","doi-asserted-by":"publisher","first-page":"1433","DOI":"10.1101\/gr.158980.113","article-title":"Interactive transcriptome analysis of malaria patients and infecting Plasmodium falciparum","volume":"24","author":"Yamagishi","year":"2014","journal-title":"Genome Res."},{"key":"B60","doi-asserted-by":"publisher","first-page":"1255","DOI":"10.1093\/molbev\/msv016","article-title":"The Avian Transcriptome Response to Malaria Infection","volume":"32","author":"Videvall","year":"2015","journal-title":"Mol Biol Evol."},{"key":"B61","doi-asserted-by":"publisher","first-page":"97","DOI":"10.1186\/s12864-019-5458-y","article-title":"Comparison of splenocyte microRNA expression profiles of pigs during acute and chronic toxoplasmosis","volume":"20","author":"Hou","year":"2019","journal-title":"BMC Genomics."},{"key":"B62","doi-asserted-by":"publisher","first-page":"580","DOI":"10.1086\/650310","article-title":"Expression of genes associated with immunoproteasome processing of major histocompatibility complex peptides is indicative of protection with adjuvanted RTS,S malaria vaccine","volume":"201","author":"Vahey","year":"2010","journal-title":"J Infect Dis."},{"key":"B63","doi-asserted-by":"publisher","first-page":"557","DOI":"10.3389\/fimmu.2017.00557","article-title":"Predicting RTS,S vaccine-mediated protection from transcriptomes in a malaria-challenge clinical trial","volume":"8","author":"van den Berg","year":"2017","journal-title":"Front Immunol."},{"key":"B64","doi-asserted-by":"publisher","first-page":"2425","DOI":"10.1073\/pnas.1621489114","article-title":"Systems analysis of protective immune responses to RTS,S malaria vaccination in humans","volume":"114","author":"Kazmin","year":"2017","journal-title":"Proc Natl Acad Sci."},{"key":"B65","doi-asserted-by":"publisher","first-page":"8386","DOI":"10.1038\/s41598-019-44924-7","article-title":"Whole-blood transcriptomic signatures induced during immunization by chloroquine prophylaxis and Plasmodium falciparum sporozoites","volume":"9","author":"Tran","year":"2019","journal-title":"Sci Rep."},{"key":"B66","doi-asserted-by":"publisher","first-page":"144","DOI":"10.1111\/imr.12817","article-title":"Decoding the complexities of human malaria through systems immunology","volume":"293","author":"Tran","year":"2020","journal-title":"Immunol Rev."},{"key":"B67","doi-asserted-by":"publisher","first-page":"e00479","DOI":"10.1128\/IAI.00479-17","article-title":"Controlled human malaria infection: Applications, advances, and challenges","volume":"86","author":"Stanisic","year":"2018","journal-title":"Infect Immun."},{"key":"B68","doi-asserted-by":"publisher","first-page":"30","DOI":"10.1016\/j.smim.2018.08.001","article-title":"Systems analysis of human vaccine adjuvants","volume":"39","author":"Harandi","year":"2018","journal-title":"Semin Immunol."},{"key":"B69","doi-asserted-by":"publisher","first-page":"35","DOI":"10.1038\/nri.2017.76","article-title":"Single-cell RNA sequencing to explore immune cell heterogeneity","volume":"18","author":"Papalexi","year":"2018","journal-title":"Nature Reviews Immunology."}],"container-title":["Frontiers in Veterinary Science"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fvets.2021.800361\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,1,7]],"date-time":"2022-01-07T08:20:54Z","timestamp":1641543654000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fvets.2021.800361\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,1,7]]},"references-count":69,"alternative-id":["10.3389\/fvets.2021.800361"],"URL":"https:\/\/doi.org\/10.3389\/fvets.2021.800361","relation":{},"ISSN":["2297-1769"],"issn-type":[{"value":"2297-1769","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,1,7]]},"article-number":"800361"}}