{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,13]],"date-time":"2026-10-13T06:49:51Z","timestamp":1791874191473,"version":"4.3.4"},"reference-count":49,"publisher":"Wiley","license":[{"start":{"date-parts":[[2026,10,12]],"date-time":"2026-10-12T00:00:00Z","timestamp":1791763200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"},{"start":{"date-parts":[[2026,10,12]],"date-time":"2026-10-12T00:00:00Z","timestamp":1791763200000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100020619","name":"Faculty of Veterinary Science, Chulalongkorn University","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100020619","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Journal of Fish Diseases"],"abstract":"ABSTRACT<\/jats:title>\n \n Acute hepatopancreatic necrosis disease (AHPND) is caused by a plasmid bearing strain of\n \n Vibrio parahaemolyticus<\/jats:italic>\n <\/jats:styled-content>\n (\n Vp<\/jats:italic>\n AHPND<\/jats:sub>\n ), which produces PirA and PirB toxins that specifically target and damage hepatopancreatic and epithelial cells of the shrimp gastrointestinal tract. The impact of AHPND, together with concerns regarding antibiotic resistance, has necessitated investigations into alternative forms of disease prevention. This study evaluated the protective efficacy of Ccombody, a recombinant variable lymphocyte receptor B (VLRB)\u2010based antibody targeting the PirA toxin, on immune\u2010related gene expression and survival in Pacific white shrimp (\n \n Penaeus vannamei<\/jats:italic>\n <\/jats:styled-content>\n ) challenged with\n Vp<\/jats:italic>\n AHPND<\/jats:sub>\n . Shrimp were allocated into six experimental groups, each in triplicate. Two groups served as controls fed a basal commercial diet: an unchallenged negative control and a\n Vp<\/jats:italic>\n AHPND<\/jats:sub>\n \u2010challenged positive control. An additional reference group was fed a commercial diet supplemented with IgY at 500\u2009mg\/100\u2009g feed. The remaining three treatment groups were fed diets supplemented with the Ccombody at 1, 10 or 100\u2009mg\/100\u2009g feed for 7\u2009days. At 7\u2009days post\u2010feeding (7\u2009d.p.f.), prophenoloxidase\u20102 (proPO\u20102), anti\u2010lipopolysaccharide factors\u20101 (ALF\u20101) and penaeidin\u20104 (PEN4) expression levels showed no significant differences among treatments. At 24\u2009h post\u2010infection (24\u2009h.p.i.), proPO\u20102 expression of Ccombody groups differed significantly from both the positive and negative control groups (\n p<\/jats:italic>\n \u2009<\u20090.05), while no significant differences were observed among Ccombody\u2010treated groups. ALF\u20101 expression remained unchanged across treatments. In contrast, the Ccombody 1 and 10\u2009mg\/100\u2009g feed groups showed significantly enhanced PEN4 expression compared to the positive control group (\n p<\/jats:italic>\n \u2009<\u20090.05). Notably, PEN4 expression significantly increased in Ccombody 1\u2009mg\/100\u2009g feed group at 24\u2009h.p.i. relative to 7 d.p.f. (\n p<\/jats:italic>\n \u2009<\u20090.05), whereas a decline was observed in the positive control and Ig\u2010Guard A groups. Principal component analysis (PCA) also showed the same scattering trend towards gene expression analysis at both 7\u2009d.p.f. and 24\u2009h.p.i. Dietary supplementation with Ccombody 1, 10 and 100\u2009mg\/100\u2009g feed effectively reduced the mortality rate following challenge with\n \n V. parahaemolyticus<\/jats:italic>\n <\/jats:styled-content>\n causing AHPND. All supplemented groups showed highly significant reduction in mortality compared to the positive control group (\n p<\/jats:italic>\n \u2009<\u20090.001). Among them, the 10 and 100\u2009mg\/100\u2009g feed groups exhibited the lowest mortality rates (3.70%\u2009\u00b1\u20091.28% and 3.70%\u2009\u00b1\u20093.39%, respectively). When considered alongside the immune\u2010related gene expression, these findings suggest that Ccombody has strong potential as an alternative immunoprophylaxis strategy for the prevention of\n Vp<\/jats:italic>\n AHPND<\/jats:sub>\n .\n <\/jats:p>","DOI":"10.1111\/jfd.70302","type":"journal-article","created":{"date-parts":[[2026,10,13]],"date-time":"2026-10-13T06:16:37Z","timestamp":1791872197000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Efficacy of Ccombody as an Immunoprophylaxis Strategy: Impact on Immune Gene Expression of Pacific White Shrimp (\n \n Penaeus vannamei<\/i>\n <\/scp>\n ) Against Acute Hepatopancreatic Necrosis Disease (\n AHPND<\/scp>\n )"],"prefix":"10.1111","author":[{"given":"Prawporn","family":"Thaijongrak","sequence":"first","affiliation":[{"name":"Veterinary Aquatic Animal Research Health Care Unit, Department of Clinical Science and Public Health, Faculty of Veterinary Science Mahidol University Nakhon Pathom Thailand"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kasemsuk","family":"Kitisriworapun","sequence":"additional","affiliation":[{"name":"Faculty of Veterinary Science Mahidol University Nakhon Pathom Thailand"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0005-8905-0251","authenticated-orcid":false,"given":"Theerapat","family":"Damrongsakul","sequence":"additional","affiliation":[{"name":"Faculty of Veterinary Science Mahidol University Nakhon Pathom Thailand"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0007-5719-9611","authenticated-orcid":false,"given":"Napat","family":"Huttayanan","sequence":"additional","affiliation":[{"name":"Faculty of Veterinary Science Mahidol University Nakhon Pathom Thailand"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thitipan","family":"Juntong","sequence":"additional","affiliation":[{"name":"Faculty of Veterinary Science Mahidol University Nakhon Pathom Thailand"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5487-7607","authenticated-orcid":false,"given":"Andrew P.","family":"Shinn","sequence":"additional","affiliation":[{"name":"INVE Aquaculture (Thailand) Pakkred Nonthaburi Thailand"},{"name":"Center of Excellence in Fish Infectious Diseases (CE FID), Faculty of Veterinary Science Chulalongkorn University Bangkok Thailand"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tae Sung","family":"Jung","sequence":"additional","affiliation":[{"name":"Earwyn Bio Co. Ltd. Jinju Gyeongnam Republic of Korea"},{"name":"Laboratory of Aquatic Animal Diseases, Institute of Animal Medicine, College of Veterinary Medicine Gyeongsang National University Jinju\u2010si Gyeongsangnam\u2010do Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Surasak","family":"Jittakhot","sequence":"additional","affiliation":[{"name":"Department of Preclinic and Applied Animal Science, Faculty of Veterinary Science Mahidol University Nakhon Pathom Thailand"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3900-0812","authenticated-orcid":false,"given":"Wanna","family":"Sirimanapong","sequence":"additional","affiliation":[{"name":"Veterinary Aquatic Animal Research Health Care Unit, Department of Clinical Science and Public Health, Faculty of Veterinary Science Mahidol University Nakhon Pathom Thailand"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,10,12]]},"reference":[{"issue":"1","key":"e_1_2_11_2_1","doi-asserted-by":"crossref","first-page":"59","DOI":"10.1016\/j.dci.2008.07.017","article-title":"A Novel Prophenoloxidase 2 Exists in Shrimp Hemocytes","volume":"33","author":"Ai H.\u2010S.","year":"2009","journal-title":"Developmental and Comparative Immunology"},{"key":"e_1_2_11_3_1","doi-asserted-by":"crossref","first-page":"203","DOI":"10.1146\/annurev-immunol-020711-075038","article-title":"VLR\u2010Based Adaptive Immunity","volume":"30","author":"Boehm T.","year":"2012","journal-title":"Annual Review of Immunology"},{"key":"e_1_2_11_4_1","doi-asserted-by":"crossref","first-page":"371","DOI":"10.1016\/j.dci.2018.03.010","article-title":"Hemocyanin of \n Litopenaeus vannamei\n Agglutinates \n Vibrio parahaemolyticus\n AHPND (VP\n AHPND) and Neutralizes Its Toxin","volume":"84","author":"Boonchuen P.","year":"2018","journal-title":"Developmental and Comparative Immunology"},{"issue":"4","key":"e_1_2_11_5_1","doi-asserted-by":"crossref","first-page":"557","DOI":"10.1016\/S1532-0456(02)00125-4","article-title":"Superoxide Dismutase as Modulator of Immune Function in American White Shrimp (\n Litopenaeus vannamei\n )","volume":"133","author":"Campa\u2010C\u00f3rdova A.","year":"2002","journal-title":"Comparative Biochemistry and Physiology. 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M. M.","year":"2023","journal-title":"Fish & Shellfish Immunology"},{"key":"e_1_2_11_12_1","doi-asserted-by":"crossref","DOI":"10.1016\/j.jip.2025.108488","article-title":"Oral Administration of Egg Yolk Immunoglobulin (IgY) in \n Penaeus vannamei\n to Combat Against Vp\n AHPND Infections","volume":"214","author":"Jiang G.","year":"2025","journal-title":"Journal of Invertebrate Pathology"},{"issue":"1","key":"e_1_2_11_13_1","first-page":"1","article-title":"Effects of IgY Antibody on Growth, Survival, Immune Responses and Protection Against \n Vibrio parahaemolyticus\n in Pacific White Shrimp","volume":"45","author":"Keetanon A.","year":"2021","journal-title":"Journal of Fisheries and Environment"},{"issue":"2","key":"e_1_2_11_14_1","doi-asserted-by":"crossref","first-page":"362","DOI":"10.1111\/are.12319","article-title":"Effect of Bioflocs on Growth and Immune Activity of Pacific White Shrimp, \n Litopenaeus vannamei\n Postlarvae","volume":"45","author":"Kim S. K.","year":"2014","journal-title":"Aquaculture Research"},{"issue":"8","key":"e_1_2_11_15_1","doi-asserted-by":"crossref","DOI":"10.3390\/toxins13080524","article-title":"Acute Hepatopancreatic Necrosis Disease (AHPND): Virulence, Pathogenesis and Mitigation Strategies in Shrimp Aquaculture","volume":"13","author":"Kumar V.","year":"2021","journal-title":"Toxins"},{"key":"e_1_2_11_16_1","doi-asserted-by":"crossref","first-page":"246","DOI":"10.1016\/j.fsi.2022.07.047","article-title":"The Production and Influence of Anti\u2010Vibrio parahaemolytics IgY against experimental infection of \n V. parahaemolyticus\n in Cultured \n Fenneropenaeus indicus","volume":"128","author":"Kumaran T.","year":"2022","journal-title":"Fish & Shellfish Immunology"},{"issue":"1","key":"e_1_2_11_17_1","article-title":"Probiotics as Antiviral Agents in Shrimp Aquaculture","volume":"2013","author":"Lakshmi B.","year":"2013","journal-title":"Journal of Pathogens"},{"issue":"1","key":"e_1_2_11_18_1","doi-asserted-by":"crossref","first-page":"55","DOI":"10.3390\/vaccines9010055","article-title":"Passive Immunization With Recombinant Antibody VLRB\u2010PirAvp\/PirBvp\u2010Enriched Feeds Against \n Vibrio parahaemolyticus\n Infection in \n Litopenaeus vannamei\n Shrimp","volume":"9","author":"Lazarte J. M. S.","year":"2021","journal-title":"Vaccine"},{"key":"e_1_2_11_19_1","doi-asserted-by":"crossref","first-page":"148","DOI":"10.1016\/j.rinim.2012.07.001","article-title":"Modulation of Innate Immunity and Gene Expressions in White Shrimp \n Litopenaeus vannamei\n Following Long\u2010Term Starvation and Re\u2010Feeding","volume":"2","author":"Lin Y.\u2010C.","year":"2012","journal-title":"Results in Immunology"},{"issue":"1","key":"e_1_2_11_20_1","doi-asserted-by":"crossref","first-page":"2248","DOI":"10.1038\/s41598-023-29225-4","article-title":"Improving Red\u2010Color Performance, Immune Response and Resistance to \n Vibrio parahaemolyticus\n on White Shrimp \n Penaeus vannamei\n by an Engineered Astaxanthin Yeast","volume":"13","author":"Lin Y.\u2010J.","year":"2023","journal-title":"Scientific Reports"},{"key":"e_1_2_11_21_1","doi-asserted-by":"crossref","DOI":"10.1016\/j.dci.2025.105429","article-title":"VP\n AHPND Pathogenesis and Its Mediated Immune Response in Shrimp","author":"Liu H.","year":"2025","journal-title":"Developmental and Comparative Immunology"},{"key":"e_1_2_11_22_1","doi-asserted-by":"crossref","DOI":"10.1016\/j.fsi.2024.109472","article-title":"Cellular and Transcriptomic Response to Pathogenic and Non\u2010Pathogenic \n Vibrio parahaemolyticus\n Strains Causing Acute Hepatopancreatic Necrosis Disease (AHPND) in \n Litopenaeus vannamei","volume":"148","author":"L\u00f3pez\u2010Landavery E. A.","year":"2024","journal-title":"Fish & Shellfish Immunology"},{"issue":"2","key":"e_1_2_11_23_1","doi-asserted-by":"crossref","first-page":"137","DOI":"10.1016\/j.fsi.2004.09.006","article-title":"Innate Immunity of Fish (Overview)","volume":"20","author":"Magnad\u00f3ttir B.","year":"2006","journal-title":"Fish & Shellfish Immunology"},{"key":"e_1_2_11_24_1","doi-asserted-by":"crossref","DOI":"10.3389\/fimmu.2021.634152","article-title":"Differentially Expressed Genes in Hepatopancreas of Acute Hepatopancreatic Necrosis Disease Tolerant and Susceptible Shrimp (\n Penaeus vannamei\n )","volume":"12","author":"Mai H. N.","year":"2021","journal-title":"Frontiers in Immunology"},{"key":"e_1_2_11_25_1","doi-asserted-by":"crossref","DOI":"10.1016\/j.aquaculture.2023.740266","article-title":"Terminalia catappa\n L. Leaf Extract Interferes With Biofilm Formation of Vibrio parahaemolyticus and Enhances Immune Response of \n Penaeus vannamei\n Against Acute Hepatopancreatic Necrosis Disease (AHPND)","volume":"579","author":"Mantaring S. D.","year":"2024","journal-title":"Aquaculture"},{"key":"e_1_2_11_26_1","doi-asserted-by":"crossref","first-page":"284","DOI":"10.1016\/j.fsi.2018.06.054","article-title":"Differentially Expressed Genes in Hemocytes of \n Litopenaeus vannamei\n Challenged With \n Vibrio parahaemolyticus\n AHPND (VP\n AHPND) and VP\n AHPND Toxin","volume":"81","author":"Maralit B. A.","year":"2018","journal-title":"Fish & Shellfish Immunology"},{"key":"e_1_2_11_27_1","first-page":"1","volume-title":"Marine Water Quality Standard","author":"Marine Environment Division. Water Quality Management Bureau. Pollution Control Department, Ministry of Natural Resources and Environment","year":"2006"},{"issue":"11","key":"e_1_2_11_28_1","doi-asserted-by":"crossref","first-page":"2678","DOI":"10.1046\/j.1432-1033.2002.02934.x","article-title":"Expression and Distribution of Penaeidin Antimicrobial Peptides Are Regulated by Haemocyte Reactions in Microbial Challenged Shrimp","volume":"269","author":"Mu\u00f1oz M.","year":"2002","journal-title":"European Journal of Biochemistry"},{"issue":"1","key":"e_1_2_11_29_1","doi-asserted-by":"crossref","first-page":"68","DOI":"10.1016\/j.fsi.2006.03.013","article-title":"Effects of Lipopolysaccharide on Gene Expression of Antimicrobial Peptides (Penaeidins and Crustin), Serine Proteinase and Prophenoloxidase in Haemocytes of the Pacific White Shrimp, \n Litopenaeus vannamei","volume":"22","author":"Okumura T.","year":"2007","journal-title":"Fish & Shellfish Immunology"},{"issue":"1","key":"e_1_2_11_30_1","doi-asserted-by":"crossref","first-page":"75","DOI":"10.1016\/j.gene.2005.11.028","article-title":"Genomic Structure and Transcriptional Regulation of the Penaeidin Gene Family From \n Litopenaeus vannamei","volume":"371","author":"O'Leary N. A.","year":"2006","journal-title":"Gene"},{"key":"e_1_2_11_31_1","doi-asserted-by":"crossref","DOI":"10.1016\/j.fsi.2024.109507","article-title":"Survival, Immune Response and Growth of Penaeid Shrimp as Affected by Immunostimulants: A Meta\u2010Analysis","volume":"148","author":"Saleh M. I. Y.","year":"2024","journal-title":"Fish & Shellfish Immunology"},{"issue":"1","key":"e_1_2_11_32_1","doi-asserted-by":"crossref","first-page":"169","DOI":"10.1007\/s10499-019-00451-w","article-title":"Diagnosis and Potential Treatments for Acute Hepatopancreatic Necrosis Disease (AHPND): A Review","volume":"28","author":"Santos H. M.","year":"2020","journal-title":"Aquaculture International"},{"key":"e_1_2_11_33_1","doi-asserted-by":"crossref","DOI":"10.1016\/j.fsi.2024.109973","article-title":"Passive Immunoprophylaxis With Ccombodies Against \n Vibrio parahaemolyticus\n in Pacific White Shrimp (\n Penaeus vannamei\n )","volume":"154","author":"Sirimanapong W.","year":"2024","journal-title":"Fish & Shellfish Immunology"},{"key":"e_1_2_11_34_1","first-page":"79","volume-title":"Current Status and Impact of Early Mortality Syndrome (EMS)\/Acute Hepatopancreatic Necrosis Disease (AHPND) and Hepatopancreatic Microsporidiosis (HPM) Outbreaks on Thailand's Shrimp Farming","author":"Songsangjinda P.","year":"2016"},{"issue":"5","key":"e_1_2_11_35_1","doi-asserted-by":"crossref","first-page":"1689","DOI":"10.1128\/AEM.03610-14","article-title":"Field and Experimental Evidence of \n Vibrio parahaemolyticus\n as the Causative Agent of Acute Hepatopancreatic Necrosis Disease of Cultured Shrimp (\n Litopenaeus vannamei\n ) in Northwestern Mexico","volume":"81","author":"Soto\u2010Rodriguez S. A.","year":"2015","journal-title":"Applied and Environmental Microbiology"},{"key":"e_1_2_11_36_1","doi-asserted-by":"crossref","DOI":"10.1177\/25151355241264520","article-title":"Monoclonal IgY Antibodies: Advancements and Limitations for Immunodiagnosis and Immunotherapy Applications","volume":"12","author":"Tabll A. 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V.","year":"2018","journal-title":"Latin American Journal of Aquatic Research"},{"issue":"1","key":"e_1_2_11_40_1","doi-asserted-by":"crossref","first-page":"53","DOI":"10.1007\/s10499-022-00966-9","article-title":"Immune Response, Gene Expression, and Intestinal Microbial Composition of Pacific White Shrimp Fed With Multispecies Synbiotic for the Prevention of Coinfection Disease","volume":"31","author":"Utomo A. S.","year":"2023","journal-title":"Aquaculture International"},{"issue":"1","key":"e_1_2_11_41_1","doi-asserted-by":"crossref","first-page":"S139","DOI":"10.3391\/ai.2011.6.S1.031","article-title":"Presence of Pacific White Shrimp \n Litopenaeus vannamei\n (Boone, 1931) in the Southern Gulf of Mexico","volume":"6","author":"Wakida\u2010Kusunoki A. T.","year":"2011","journal-title":"Aquatic Invasions"},{"issue":"3","key":"e_1_2_11_42_1","doi-asserted-by":"crossref","first-page":"266","DOI":"10.1016\/j.dci.2013.02.011","article-title":"Litopenaeus vannamei\n Toll\u2010Interacting Protein (LvTollip) is a Potential Negative Regulator of the Shrimp Toll Pathway Involved in the Regulation of the Shrimp Antimicrobial Peptide Gene Penaeidin\u20104 (PEN4)","volume":"40","author":"Wang P. 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