以疫苗來控制疾病具有使用成本低，疾病防治效果佳，以及保護時間長等優點。因此在量產養殖漁業上運用疫苗控制疾病問題漸顯重要。相關研究亦顯示諸多不活化疫苗已經被證實可以有效控制魚隻疾病問題。然而對魚類接受疫苗後所引起的免疫反應不甚了解，因此在魚類使用疫苗後所引起的免疫反應缺乏相關資訊可參考，使得研發時程需時較長的問題。因此，本研究將首先探討魚類在注射疫苗後的免疫相關基因表現，透過不同時間所誘發的基因表現，來推測疫苗所引起的反應路徑。其次，在分析疫苗所誘發之免疫基因及疫苗保護力之間的關聯性後，從而找到可能具有誘導有效免疫反應的候選因子。在最後，這些候選因子將以重組蛋白形式添加於疫苗之中，以確認這些因子是否能增進疫苗的保護力。在結果中發現疫苗注射的確可以誘發魚類體內 Th1 及 Th2 淋巴球分化，進而產生功能細胞 (effector cell)，這些反應與疫苗保護力有高度相關。其次發現能誘發這些路徑的免疫因子則可以增進疫苗的保護力。我們認為本研究的成果可以提供未來疫苗開發上的參考。加速魚用疫苗研發之時程，並建立完善使用疫苗前後評估標準，最終於整個養殖漁業永續發展。

Disease control is an important issue in aquaculture industry. Using vaccine to control disease is advantaged in low cost, high efficiency, and long protection period; so vaccination is playing more important role in aquaculture disease control methods. However, since the few understand of the fish immunology, fish vaccine was still developing with a trial and error method until today. In this study, we try to explore the immune related genes expression in vaccination incubation period, which might figure out the major possible immune pathway in the vaccination reaction. Furthermore, compare the survival rate in challenge trial, and try to identify the index genes highly expressed and relative with the vaccine potection. Finally, we try to increasing these candidate moleculars by exogenous addition recombinant proteins in the vaccine, and evaluated which critical moleculars are increase the efficacy of the fish vaccine. The results of this study revealed the Th1 and Th2 lymphocyte was proliferated in the vaccine injected fish and the effector was further generated; these processed was essential for the potency of vaccine. Addition these moleculars in the vaccine was truly increasing the survival rate in the pathogen challenge test. These results will give more understanding of fish immune reaction in vaccine inoculation. And the addition of fish immune molecular in the vaccine might be a new way to increase fish vaccine efficacy.

水產試驗所，歷年石斑魚魚苗產量，行政院農業委員會，2014。

陳信宏，點帶石斑魚介白素-6 之基因轉殖、蛋白表現及功能分析，國立成功大學生物科技研究所碩士論文，2011。

Akkermans, A. M., Hendriksen, C. F., Marsman, F. R. and van de Donk, H. J. Evaluation and validation of a single-dilution potency assay based upon serology of vaccines containing diphtheria toxoid: analysis for consistency in production and testing. Developments in Biological Standardization 86, 323-324, 1996.

Alberts, B., Johnson, A., Lewis, J., Raff, M., Roberts, K. and Walter, P. The Adaptive Immune System. Molecular Biology of the Cell, Garland Science, New York, 1321-1375, 2002.

Amanna, I. J. and Slifka, M. K. Contributions of humoral and cellular immunity to vaccine-induced protection in humans. Virology 411, 206-215, 2011.

Andre, F. E., Booy, R., Bock, H. L., Clemens, J., Datta, S. K., John, T. J., Lee, B. W., Lolekha, S., Peltola, H., Ruff, T. A., Santosham, M. and Schmitt, H. J. Vaccination greatly reduces disease, disability, death and inequity worldwide. Bulletin of the World Health Organization 86, 140-146, 2008.

Arts, J. A. J., Tijhaar, E. J., Chadzinska, M., Savelkoul, H. F. J. and Verburg-van Kemenade, B. M. L. Functional analysis of carp interferon-gamma: Evolutionary conservation of classical phagocyte activation. Fish and Shellfish Immunology 29, 793-802, 2010.

Balamurugan, V., Kumar, R. M. and Suryanarayana, V. V. Past and present vaccine development strategies for the control of foot-and-mouth disease. Acta Virologica 48, 201-214, 2004.

Barton, B. A., Morgan, J. D. and Vijayan, M. M. Physiological and condition-related indicators of environmental stress in fish. Biological Indicators of Aquatic Ecosystem Stress, Centre for Agriculture and Bioscience International, Wallingford, 111-148, 2002.

Baxter, D. Active and passive immunity, vaccine types, excipients and licensing. Occupational Medicine-Oxford 57, 552-556, 2007.

Bhattach, P. and Mukerjee, S. Further studies on development of a live oral cholera vaccine. Journal of Hygiene-Cambridge 66, 307-318, 1968.

Broere, F., Apasov, S. G., Sitkovsky, M. V. and Eden, W. T cell subsets and T cell-mediated immunity. Principles of Immunopharmacology, Springer, New York, 15-27, 2011.

Burton, D. R. Antibodies, viruses and vaccines. Nature Reviews Immunology 2. Springer Nature, London, 706-713, 2002.

Castro, R., Jouneau, L., Pham, H. P., Bouchez, O., Giudicelli, V., Lefranc, M. P., Quillet, E., Benmansour, A., Cazals, E., Six, A., Fillatreau, S., Sunyer, O. and Boudinot, P. Teleost fish mount complex clonal IgM and IgT responses in spleen upon systemic viral infection. Fish and Shellfish Immunology 34, 1643-1644, 2013.

Cecchini, S. and Saroglia, M. Antibody response in sea bass (Dicentrarchus labrax L.) in relation to water temperature and oxygenation. Aquaculture Research 33, 607-613, 2002.

Chalamaiah, M., Kumar, B. D., Hemalatha, R. and Jyothirmayi, T. Fish protein hydrolysates: Proximate composition, amino acid composition, antioxidant activities and applications- A review. Food Chemistry 135, 3020-3038, 2012.

Chen, H. H., Lin, H. T., Foung, Y. F. and Lin, J. H. Y. The bioactivity of teleost IL-6: IL-6 protein in orange-spotted grouper (Epinephelus coioides) induces Th2 cell differentiation pathway and antibody production. Developmental and Comparative Immunology 38, 285-294, 2012.

Chen, Q., Ghilardi, N., Wang, H., Baker, T., Xie, M. H., Gurney, A., Grewal, I. S. and de Sauvage, F. J. Development of Th1-type immune responses requires the type I cytokine receptor TCCR. Nature 407, 916-920, 2000.

Chen, X., Bailleux, F., Desai, K., Qin, L. and Dunning, A. J. A threshold method for immunological correlates of protection. Biomed Central Medical Research Methodology 13, 1-10, 2013.

Cheng, A. C., Cheng, S. A., Chen, Y. Y. and Chen, J. C. Effects of temperature change on the innate cellular and humoral immune responses of orange-spotted grouper Epinephelus coioides and its susceptibility to Vibrio alginolyticus. Fish and Shellfish Immunology 26, 768-772, 2009.

Cheng, C. A., John, J. A. C., Wu, M. S., Lee, C. Y., Lin, C. H., Lin, C. H. and Chang, C. Y. Characterization of serum immunoglobulin M of grouper and cDNA cloning of its heavy chain. Veterinary Immunology and Immunopathology 109, 255-265, 2006.

Choi, J. P., Kim, Y. S., Kim, O. Y., Kim, Y. M., Jeon, S. G., Roh, T. Y., Park, J. S., Gho, Y. S. and Kim, Y. K. TNF-alpha is a key mediator in the development of Th2 cell response to inhaled allergens induced by a viral PAMP double-stranded RNA. Allergy 67, 1138-1148, 2012.

Chua, B. Y., Wong, C. Y., Mifsud, E. J., Edenborough, K. M., Sekiya, T., Tan, A. C. L., Mercuri, F., Rockman, S., Chen, W. and Turner, S. J. Inactivated influenza vaccine that provides rapid, innate-immune-system-mediated protection and subsequent long-term adaptive immunity. mBio 6, e01024-1038, 2015.

Cichon, M., Chadzinska, M., Ksiazek, A. and Konarzewski, M. Delayed effects of cold stress on immune response in laboratory mice. Proceedings of the Royal Society B-Biological Sciences 269, 1493-1497, 2002.

Clark, J., Vagenas, P., Panesar, M. and Cope, A. P. What does tumour necrosis factor excess do to the immune system long term? Annals of the Rheumatic Diseases 64, 70-76, 2005.

Cossarini-Dunier, M. Effect of different adjuvants on the humoral immune response of rainbow trout. Developmental and Comparative Immunology 9, 141-146, 1985.

Demas, G. E., Chefer, V., Talan, M. I. and Nelson, R. J. Metabolic costs of mounting an antigen-stimulated immune response in adult and aged C57BL/6J mice. American Journal of Physiology-Regulatory Integrative and Comparative Physiology 273, 1631-1637, 1997.

Di Pasquale, A., Preiss, S., Da Silva, F. T. and Garcon, N. Vaccine Adjuvants: from 1920 to 2015 and Beyond. Vaccines 3, 320-343, 2015.

Diehl, S. and Rincon, M. The two faces of IL-6 on Th1/Th2 differentiation. Molecular Immunology 39, 531-536, 2002.

Dijkstra, J. M., Katagiri, T., Hosomichi, K., Yanagiya, K., Inoko, H., Ototake, M., Aoki, T., Hashimoto, K. and Shiina, T. A third broad lineage of major histocompatibility complex (MHC) class I in teleost fish; MHC class II linkage and processed genes. Immunogenetics 59, 305-321, 2007.

Dudley, D. J. The immune-system in health and disease. Baillieres Clinical Obstetrics and Gynaecology 6, 393-416, 1992.

Duff, D. C. B. The oral immunization of trout against Bacterium salmonicida. Journal of Immunology 44, 87-94, 1942.

Dunier, M. and Siwicki, A. K. Effects of pesticides and other organic pollutants in the aquatic environment on immunity of fish - a review. Fish and Shellfish Immunology 3, 423-438, 1993.

Erickson, K. L., Medina, E. A. and Hubbard, N. E. Micronutrients and innate immunity. Journal of Infectious Diseases 182, 5-10, 2000.

Evelyn, T. P. A historical review of fish vaccinology. Developments in Biological Standardization 90, 3-12, 1997.

Faber, H. K. Poliomyelitis Vaccine. Jama-Journal of the American Medical Association 172, 1677, 1960.

Figueras, A., Santarem, M. M. and Novoa, B. Influence of the sequence of administration of beta-glucans and a Vibrio damsela vaccine on the immune response of turbot (Scophthalmus maximus L.). Veterinary Immunology and Immunopathology 64, 59-68, 1998.

Food and Agriculture Organization of the United Nations. Improved preparedness for and effective response to disasters in fisheries and aquaculture. The State of World Fisheries and Aquaculture. Food and Agriculture Organization of the United Nations, Rome, 114-121, 2012.

Food and Agriculture Organization of the United Nations. Aquaculture Development. Food and Agriculture Organization of the United Nations, Rome, 1-6, 2011.

Food and Agriculture Organization of the United Nations. Global overview. Review of the State of World Marine Fishery Resources. Food and Agriculture Organization of the United Nations, Rome, 1-3, 2014.

Fredriksen, B. N., Olsen, R. H., Furevik, A., Souhoka, R. A., Gauthier, D. and Brudeseth, B. Efficacy of a divalent and a multivalent water-in-oil formulated vaccine against a highly virulent strain of Flavobacterium psychrophilum after intramuscular challenge of rainbow trout (Oncorhynchus mykiss). Vaccine 31, 1994-1998, 2013.

Galindo-Villegas, J., Mulero, I., Garcia-Alcazar, A., Munoz, I., Penalver-Mellado, M., Streitenberger, S., Scapigliati, G., Meseguer, J. and Mulero, V. Recombinant TNF alpha as oral vaccine adjuvant protects European sea bass against vibriosis: Insights into the role of the CCL25/CCR9 axis. Fish and Shellfish Immunology 35, 1260-1271, 2013.

Galli, G., Medini, D., Borgogni, E., Zedda, L., Bardelli, M., Malzone, C., Nuti, S., Tavarini, S., Sammicheli, C. and Hilbert, A. K. Adjuvanted H5N1 vaccine induces early CD4+ T cell response that predicts long-term persistence of protective antibody levels. Proceedings of the National Academy of Sciences of the United States of America 106, 3877-3882, 2009.

Gary, O. Introduction. The Laboratory Fish. Academic Press, California, 1-9, 2000.

Gautier, M., Faraut, T., Moazami-Goudarzi, K., Navratil, V., Fogfio, M., Grohs, C., Boland, A., Garnier, J. G., Boichard, D., Lathrop, G. M., Gut, I. G. and Eggen, A. Genetic and haplotypic structure in 14 European and African cattle breeds. Genetics 177, 1059-1070, 2007.

Glimcher, L. H. and Murphy, K. M. Lineage commitment in the immune system: the T helper lymphocyte grows up. Genes and Development 14, 1693-1711, 2000.

Grayfer, L., Garcia, E. G. and Belosevic, M. Comparison of macrophage antimicrobial responses induced by type II interferons of the Goldfish (Carassius auratus L.). Journal of Biological Chemistry 285, 23537-23547, 2010.

Grayfer, L., Hodgkinson, J. W., Hitchen, S. J. and Belosevic, M. Characterization and functional analysis of goldfish (Carassius auratus L.) interleukin-10. Molecular Immunology 48, 563-571, 2011.

Gulnihal, O., Grant, B. and Taworn, T. Impacts of aquaculture on habitats and best management practices (BMPs). Sustainable Aquaculture Techniques, Martha Patricia Hernandez, Croatia, 1-28, 2014.

Harikrishnan, R., Balasundaram, C. and Heo, M. S. Molecular studies, disease status and prophylactic measures in grouper aquaculture: Economic importance, diseases and immunology. Aquaculture 309, 1-14, 2010.

Heath, A. W. and Playfair, J. H. L. Conjugation of interferon-gamma to antigen enhances its adjuvanticity. Immunology 71, 454-456, 1990.

Henry, M. Multiple sclerosis and vaccine. Jama-Journal of the American Medical Association 162, 1019, 1956.

Hirota, Y., Kaji, M., Ide, S., Kajiwara, J., Kataoka, K., Goto, S. and Oka, T. Antibody efficacy as a keen index to evaluate influenza vaccine effectiveness. Vaccine 15, 962-967, 1997.

Hughes, J. Hypodermic Injection. American Journal of Nursing 17, 198-200, 1916.

Ipsen, J. The effect of environmental temperature on the immune response of mice to tetanus toxoid. Journal of Immunology 69, 273-283, 1952.

Itano, T., Kawakami, H., Kono, T. and Sakai, M. Live vaccine trials against nocardiosis in yellowtail Seriola quinqueradiata. Aquaculture 261, 1175-1180, 2006.

Jacobs, A. The pathologies of big data. Communications of the Acm 52, 36-44, 2009.

Janeway, C. A. and Medzhitov, R. Innate immune recognition. Annual Review of Immunology 20, 197-216, 2002.

Janeway, C. A., Travers, P. l., Walport, M. J. and Shlomchik, M. J. The immune system in health and disease. Immunobiology. Churchill Livingstone. London. 185-211, 2001.

Jones, S. A. Directing transition from innate to acquired immunity defining a role for IL-6. Journal of Immunology 175, 3463-3468, 2005.

Jorgensen, J. B., Zou, J., Johansen, A. and Secombes, C. J. Immunostimulatory CpG oligodeoxynucleotides stimulate expression of IL-1 beta and interferon-like cytokines in rainbow trout macrophages via a chloroquine-sensitive mechanism. Fish and Shellfish Immunology 11, 673-682, 2001.

Kaper, J. B. Vibrio-cholerae vaccines. Reviews of Infectious Diseases 11, 568-573, 1989.

Kataoka, M., Toyoizumi, H., Yamamoto, A., Ochiai, M. and Horiuchi, Y. Chinese hamster ovary (CHO) cell clustering does not correlate with in vivo histamine-sensitization when measuring residual activity of aldehyde-treated pertussis toxin (PT). Biologicals 30, 297-302, 2002.

Kaur, R. and Vrati, S. Development of a recombinant vaccine against Japanese encephalitis. Journal of Neurovirology 9, 421-431, 2003.

Keitel, W. A., Atmar, R. L., Cate, T. R., Petersen, N. J., Greenberg, S. B., Ruben, F. and Couch, R. B. Safety of high doses of influenza vaccine and effect on antibody responses in elderly persons. Archives of Internal Medicine 166, 1121-1127, 2006.

Kim, H. J., Oseko, N., Nishizawa, T. and Yoshimizu, M. Protection of rainbow trout from infectious hematopoietic necrosis (IHN) by injection of infectious pancreatic necrosis virus (IPNV) or Poly(I:C). Diseases of Aquatic Organisms 83, 105-113, 2009.

Kiron, V. Fish immune system and its nutritional modulation for preventive health care. Animal Feed Science and Technology 173, 111-133, 2012.

Kitchin, R. Big data and human geography Opportunities, challenges and risks. Dialogues in Human Geography 3, 262-267, 2013.

Kurogi, H., Inaba, Y., Takahashi, E., Sato, K., Goto, Y., Satoda, K., Omori, T. and Hatakeyama, H. Development of inactivated vaccine for Akabane disease. National Institute of Animal Health Quarterly 18, 97-108, 1978.

Lambert, P. H., Liu, M. and Siegrist, C. A. Can successful vaccines teach us how to induce efficient protective immune responses? Nature Medicine 11, 54-62, 2005.

Landolt, M. L. The relationship between diet and the immune-response of fish. Aquaculture 79, 193-206, 1989.

Le Morvan, C., Troutaud, D. and Deschaux, P. Differential effects of temperature on specific and nonspecific immune defences in fish. Journal of Experimental Biology 201, 165-168, 1998.

Le Moullac, G. and Haffner, P. Environmental factors affecting immune responses in Crustacea. Aquaculture 191, 121-131, 2000.

Lee, A. Animal-models and vaccine development. Baillieres Clinical Gastroenterology 9, 615-632, 1995.

Leo, O., Cunningham, A. and Stern, P. L. Vaccine immunology. Perspectives in Vaccinology 1, 25-59, 2011.

Lin, A. F., Xiang, L. X., Wang, Q. L., Dong, W. R., Gong, Y. F. and Shao, J. Z. The DC-SIGN of zebrafish: Insights into the existence of a CD209 homologue in a lower vertebrate and its involvement in adaptive immunity. Journal of Immunology 183, 7398-7410, 2009.

Lin, C. C., Lin, J. H. Y., Chen, M. S. and Yang, H. L. An oral nervous necrosis virus vaccine that induces protective immunity in larvae of grouper (Epinephelus coioides). Aquaculture 268, 265-273, 2007.

Lombard, M., Pastoret, P. P. and Moulin, A. M. A brief history of vaccines and vaccination. Revue Scientifique et Technique 26, 29-48, 2007.

Mackay, I. R., Rosen, F. S., Delves, P. J. and Roitt, I. M. The immune system. New England Journal of Medicine 343, 37-49, 2000.

Magnadottir, B. Innate immunity of fish -overview. Fish and Shellfish Immunology 20, 137-151, 2006.

Magnadottir, B. Immunological control of fish diseases. Marine Biotechnology 12, 361-379, 2010.

Magnadottir, B., Jonsdottir, H., Helgason, S., Bjornsson, B., Jorgensen, T. O. and Pilstrom, L. Humoral immune parameters in Atlantic cod (Gadus morhua L.) - I. The effects of environmental temperature. Comparative Biochemistry and Physiology B-Biochemistry and Molecular Biology 122, 173-180, 1999.

Mahul, O. and Gohin, A. Irreversible decision making in contagious animal disease control under uncertainty: an illustration using FMD in Brittany. European Review of Agricultural Economics 26, 39-58, 1999.

Marcos, A., Nova, E. and Montero, A. Changes in the immune system are conditioned by nutrition. European Journal of Clinical Nutrition 57, 66-69, 2003.

Martin, S. A. M., Taggart, J. B., Seear, P., Bron, J. E., Talbot, R., Teale, A. J., Sweeney, G. E., Hoyheim, B., Houlihan, D. F., Tocher, D. R., Zou, J. and Secombes, C. J. Interferon type I and type II responses in an Atlantic salmon (Salmo salar) SHK-1 cell line by the salmon TRAITS/SGP microarray. Physiological Genomics 32, 33-44, 2007a.

Martin, S. A. M., Zou, J., Houlihan, D. F. and Secombes, C. J. Directional responses following recombinant cytokine stimulation of rainbow trout (Oncorhynchus mykiss) RTS-II macrophage cells as revealed by transcriptome profiling. Biomed Central Genomics 8, 1-18, 2007b.

Martins, M. L., Xu, D. H., Shoemaker, C. A. and Klesius, P. H. Temperature effects on immune response and hematological parameters of channel catfish Ictalurus punctatus vaccinated with live theronts of Ichthyophthirius multifiliis. Fish and Shellfish Immunology 31, 774-780, 2011.

McCullough, K. C. and Summerfield, A. Basic concepts of immune response and defense development. Ilar Journal 46, 230-240, 2005.

McFarlane, H. and Path, M. R. C. Immunological aspects of staphylococcal enterotoxins. Immunological Aspects of Foods. Westport, New York, 199-220, 1977.

Metlin, A., Paulin, L., Suomalainen, S., Neuvonen, E., Rybakov, S., Mikhalishin, V. and Huovilainen, A. Characterization of Russian rabies virus vaccine strain RV-97. Virus Research 132, 242-247, 2008.

Monte, M. M., Wang, T. H., Costa, M. M., Harun, N. O. and Secombes, C. J. Cloning and expression analysis of two ROR-gamma homologues (ROR-gamma a1 and ROR-gamma a2) in rainbow trout Oncorhynchus mykiss. Fish and Shellfish Immunology 33, 365-374, 2012.

Nakanishi, T., Shibasaki, Y. and Matsuura, Y. T cells in fish. Biology 4, 640-663, 2015.

Nardocci, G., Navarro, C., Cortes, P. P., Imarai, M., Montoya, M., Valenzuela, B., Jara, P., Acuna-Castillo, C. and Fernandez, R. Neuroendocrine mechanisms for immune system regulation during stress in fish. Fish and Shellfish Immunology 40, 531-538, 2014.

Nish, S. A., Schenten, D., Wunderlich, F. T., Pope, S., Gao, Y., Hoshi, N., Yu, S., Yan, X. T., Lee, H. K., Pasman, L., Brodsky, I., Yordy, B., Zhao, H. Y., Bruning, J. C. and Medzhitov, R. T cell-intrinsic role of IL-6 signaling in primary and memory responses. Elife 3, e01949, 2014.

Parkin, J. and Cohen, B. An overview of the immune system. Lancet 357, 1777-1789, 2001.

Pennock, N. D., White, J. T., Cross, E. W., Cheney, E. E., Tamburini, B. A. and Kedl, R. M. T cell responses: naive to memory and everything in between. Advances in Physiology Education 37, 273-283, 2013.

Petersen, C. Are vaccines effectie. Frequently Asked Questions about Vaccines and Vaccinations. Rosen, New York, 15-24, 2011.

Pichichero, M. E. Booster vaccinations: can immunologic memory outpace disease pathogenesis? Pediatrics 124, 1633-1641, 2009.

Plotkin, S. A. Correlates of vaccine-induced immunity. Clinical Infectious Diseases 47, 401-409, 2008.

Plotkin, S. A. Correlates of protection induced by vaccination. Clinical and Vaccine Immunology 17, 1055-1065, 2010.

Podrez, E. A., Febbraio, M., Sheibani, N., Schmitt, D., Silverstein, R. L., Hajjar, D. P., Cohen, P. A., Frazier, W. A., Hoff, H. F. and Hazen, S. L. Macrophage scavenger receptor CD36 is the major receptor for LDL modified by monocyte-generated reactive nitrogen species. Journal of Clinical Investigation 105, 1483, 2000.

Pougatcheva, S. O., Abernathy, E. S., Vzorov, A. N., Compans, R. W. and Frey, T. K. Development of a rubella virus DNA vaccine. Vaccine 17, 2104-2112, 1999.

Ramkumar, T. P., Hammache, D. and Stahl, P. D. The macrophage mannose receptor and innate immunity. Immunology, Springer, Totowa, 191-204, 2003.

Riedel, S. Edward Jenner and the history of smallpox and vaccination. Baylor University Medical Center 18, 21-25, 2005.

Riley, H. D., Shaw, R. F. and Bures, P. Measles vaccine - results of studies with both live and killed-virus vaccines. Journal of Pediatrics 63, 748-749, 1963.

Robbins, J. B., Schneerson, R. and Szu, S. C. Perspective - hypothesis - serum Igg antibody is sufficient to confer protection against infectious-diseases by inactivating the inoculum. Journal of Infectious Diseases 171, 1387-1398, 1995.

Roca, F. J., Mulero, I., Lopez-Munoz, A., Sepulcre, M. P., Renshaw, S. A., Meseguer, J. and Mulero, V. Evolution of the inflammatory response in vertebrates: fish TNF-alpha is a powerful activator of endothelial cells but hardly activates phagocytes. Journal of Immunology 181, 5071-5081, 2008.

Rohitayodhin, S. and Hammon, W. M. Development of attenuated strain of Japanese B encephalitis virus for possible use as a vaccine. Military Medicine 127, 567-568, 1962.

Rombout, J. H. W. M., Huttenhuis, H. B. T., Picchietti, S. and Scapigliati, G. Phylogeny and ontogeny of fish leucocytes. Fish and Shellfish Immunology 19, 441-455, 2005.

Seder, R. A., Darrah, P. A. and Roederer, M. T-cell quality in memory and protection: implications for vaccine design. Nature Reviews Immunology 8, 247-258, 2008.

Sesardic, D., Dawes, C. S., McLellan, K., Durrani, Z., Yost, S. E. and Corbel, M. J. Non-pertussis components of combination vaccines: Problems with potency testing. Biologicals 27, 177-181, 1999.

Siegrist, C. A. General aspects of vaccination. Vaccine Immunology. Elsevier, Amsterdam, 17-36, 2008.

Sommerset, I., Krossoy, B., Biering, E. and Frost, P. Vaccines for fish in aquaculture. Expert Review of Vaccines 4, 89-101, 2005.

Souto, G. R., Queiroz, C. M., de Abreu, M. H. N. G., Costa, F. O. and Mesquita, R. A. Pro-inflammatory, Th1, Th2, Th17 cytokines and dendritic cells: a cross-sectional study in chronic periodontitis. Plos One 9, e91636, 2014.

Stenger, S. and Rollinghoff, M. Role of cytokines in the innate immune response to intracellular pathogens. Annals of the Rheumatic Diseases 60, Iii43-46, 2001.

Sun, Y. and Sun, L. CsBAFF, a teleost B cell activating factor, promotes pathogen-induced innate immunity and vaccine-induced adaptive immunity. Plos One 10, e0136015, 2015.

Takeda, K. and Akira, S. Toll-like receptors in innate immunity. International Immunology 17, 1-14, 2005.

Takizawa, F., Dijkstra, J. M., Kotterba, P., Korytar, T., Kock, H., Kollner, B., Jaureguiberry, B., Nakanishi, T. and Fischer, U. The expression of CD8 alpha discriminates distinct T cell subsets in teleost fish. Developmental and Comparative Immunology 35, 752-763, 2011.

Tanaka, T., Narazaki, M. and Kishimoto, T. IL-6 in inflammation, immunity, and disease. Cold Spring Harbor Perspectives in Biology 6, a016295, 2014.

Toda, H., Saito, Y., Koike, T., Takizawa, F., Araki, K., Yabu, T., Somamoto, T., Suetake, H., Suzuki, Y., Ototake, M., Moritomo, T. and Nakanishi, T. Conservation of characteristics and functions of CD4 positive lymphocytes in a teleost fish. Developmental and Comparative Immunology 35, 650-660, 2011.

Tort, L. Stress and immune modulation in fish. Developmental and Comparative Immunology 35, 1366-1375, 2011.

Tort, L., Balasch, J. C. and Mackenzie, S. Fish immune system. A crossroads between innate and adaptive responses. Inmunologia 22, 277-286, 2003.

Tsui, W. C., Chen, J. C. and Cheng, S. Y. The effects of a sudden salinity change on cortisol, glucose, lactate, and osmolality levels in grouper Epinephelus malabaricus. Fish Physiology and Biochemistry 38, 1323-1329, 2012.

Usinger, W. R. A comparison of antibody responses to veterinary vaccine antigens potentiated by different adjuvants. Vaccine 15, 1902-1907, 1997.

Van Loveren, H., Van Amsterdam, J. G. C., Vandebriel, R. J., Kimman, T. G., Rumke, H. C., Steerenberg, P. S. and Vos, J. G. Vaccine-induced antibody responses as parameters of the influence of endogenous and environmental factors. Environmental Health Perspectives 109, 757-764, 2001.

Vilcek, J. and Feldmann, M. Historical review: cytokines as therapeutics and targets of therapeutics. Trends in Pharmacological Sciences 25, 201-209, 2004.

Villumsen, K. R., Dalsgaard, I., Holten-Andersen, L. and Raida, M. K. Potential Role of Specific Antibodies as Important Vaccine Induced Protective Mechanism against Aeromonas salmonicida in Rainbow Trout. Plos One 7, e46733, 2012.

Voelker, R. Flu vaccine in nasal spray. Jama-Journal of the American Medical Association 279, 1599, 1998.

Wang, T. H., Diaz-Rosales, P., Costa, M. M., Campbell, S., Snow, M., Collet, B., Martin, S. A. M. and Secombes, C. J. Functional characterization of a nonmammalian IL-21: rainbow trout Oncorhynchus mykiss IL-21 upregulates the expression of the Th cell signature cytokines IFN-gamma, IL-10, and IL-22. Journal of Immunology 186, 708-721, 2011.

Wang, T. H., Holland, J. W., Martin, S. A. M. and Secombes, C. J. Sequence and expression analysis of two T helper master transcription factors, T-bet and GATA3, in rainbow trout Oncorhynchus mykiss and analysis of their expression during bacterial and parasitic infection. Fish and Shellfish Immunology 29, 705-715, 2010.

Wang, T. H. and Secombes, C. J. The cytokine networks of adaptive immunity in fish. Fish and Shellfish Immunology 35, 1703-1718, 2013.

Weber, D. J., Rutala, W. A., Kenyear, S. A. and Lemon, S. M. Response to deltoid muscle injection of Hepatitis-B Vaccine after failure to respond to gluteal injections. Jama-Journal of the American Medical Association 255, 2157, 1986.

Wkly, E. R. Tetanus vaccine. The Weekly Epidemiological Record 81, 198-208, 2006.

Xu, S. W., Wu, J. Y., Hu, K. S., Ping, H. L., Duan, Z. G. and Zhang, H. F. Molecular cloning and expression of orange-spotted grouper (Epinephelus coioides) CD8 alpha and CD8 beta genes. Fish and Shellfish Immunology 30, 600-608, 2011.

Yamane, H. and Paul, W. E. Early signaling events that underlie fate decisions of naive CD4(+) T cells toward distinct T-helper cell subsets. Immunological Reviews 252, 12-23, 2013.

Yin, Z., Lam, T. J. and Sin, Y. M. The effects of crowding stress on the non-specific immuneresponse in fancy carp (Cyprinus carpio L.). Fish and Shellfish Immunology 5, 519-529, 1995.

Zapata, A., Diez, B., Cejalvo, T., Frias, C. G. and Cortes, A. Ontogeny of the immune system of fish. Fish and Shellfish Immunology 20, 126-136, 2006.

Zou, J. and Secombes, C. J. Teleost fish interferons and their role in immunity. Developmental and Comparative Immunology 35, 1376-1387, 2011.

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