Vaccination studies in aquaculture systems are strategically associated with the economically and environmentally sustainable management of aquaculture production worldwide. Historically, most licensed fish vaccines have been developed as inactivated pathogens combined with adjuvants and provided via immersion or injection. In comparison, live vaccines can simulate a whole pathogenic illness and elicit a strong immune response, making them better suited for oral or immersion-based therapy methods to control diseases. Advanced approaches in vaccine development involve targeting specific pathogenic components, including the use of recombinant genes and proteins. Vaccines produced using these techniques, some of which are currently commercially available, appear to elicit and promote higher levels of immunity than conventional fish vaccines. These technological advancements are promising for developing sustainable production processes for commercially important aquatic species.
1. Aquaculture Diseases
Infections in fish leading to disease outbreaks are a major concern for the aquaculture sector because they can result in significant economic damage owing to morbidity and death. The high fish-rearing densities currently used in aquaculture enable the transfer and spread of pathogenic microorganisms and are often a primary cause of such catastrophic outbreaks
[1]. Intensive farming practices exert huge stresses on cultured aquatic species, compromising their innate immune defenses against various disease-causing bacterial and viral pathogens. Adequate husbandry and overall management, including biosecurity, nutrition genetics, system management, and water quality, are crucial for aquaculture production in all intensive culture farming practices, irrespective of whether individual or several species of fish are produced in dense populations
[2]. In China, India, and Vietnam, fish diseases are estimated to contribute to more than 30% of the overall production loss
[3]. Several bacterial and viral pathogens and parasites are opportunistic and occur in the environment or as asymptomatic carriers on some fish, which renders aquaculture facilities highly susceptible to disease outbreaks and hinders the development of an efficient, cost-effective, and stable aquaculture process
[4]. The appearance and progression of fish disease are determined by the relationship between the pathogen, host, and environment. Stressful conditions, including high population density, change in temperature, and hypoxia, can hasten the spread of pathogenic bacteria and result in major disease outbreaks
[5]. Thus, multidisciplinary studies on the characteristics of potential fish pathogens, the biology of the fish hosts, and an adequate understanding of the global environmental factors affecting are important to investigate appropriate measures for the prevention and control of the major diseases limiting fish production in aquaculture.
2. Bacterial Pathogens of Fish
Several bacterial infections in fish species, including Aeromonas septicemia
[6], Edwardsiellosis
[7], Columnaris
[8], Streptococcosis
[9], and vibriosis
[10] have been reported in the aquaculture sector
[11]. Nevertheless, a few of these pathogens are found to be highly responsible for the majority of global economic losses in aquaculture production
[12]. Bacterial species responsible for disease outbreaks in different fish species are mentioned in
Table 1.
Aeromonas spp. are among the most common types of bacterial pathogens in numerous fish species that occur in freshwater and tropical environments and cause bacterial hemorrhage in cultured fishes
[13].
Aeromonas salmonicida is one of the oldest known fish pathogens that occurs worldwide in both fresh and marine waters aquaculture regions and is associated with skin ulceration and hemorrhages found as recurrent clinical symptoms of infection
[14][15].
Table 1. Bacterial Pathogens of Fishes.
Agents |
Disease |
Host Fish Targets |
References |
Aeromonas salmonicida |
Furunculosis |
trout, salmon, goldfish, koi, and a wide range of fish species |
[14][16][17][18] |
Aeromonas hydrophila |
Motile Aeromonas septicemia (MAS), hemorrhagic septicemia, red-sore disease, ulcer disease, epizootic ulcerative syndrome (EUS) |
tilapia, catfish, striped salmonid, non-salmonid fish, sturgeon, bass, and eel |
[14][17][18][19] |
Edwardsiella ictaluri |
Enteric septicemia |
Catfish and tilapia |
[20][21][22][23] |
Edwardsiella tarda |
Edwardsiellosis |
Salmon, carps, tilapia, catfish, striped bass, flounder, and yellowtail |
[24][25][26] |
Yersinia ruckeri |
Enteric redmouth |
Salmonids, eel, minnows, sturgeon, and crustaceans |
[27][28][29][30] |
Piscirickettsia salmonis |
Piscirickettsiosis |
Salmonids |
[30][31][32][33] |
Flavobacterium psychrophilum |
Coldwater disease |
Salmonids, carp, eel, tench, perch, ayu |
[34][35][36] |
Flavobacterium columnare |
Columnaris disease |
cyprinids, salmonids, silurids, eel, and sturgeon |
[37][38][39] |
Pseudomonas anguilliseptica |
Pseudomonadiasis, winter disease |
Sea bream, eel, turbot, and ayu |
[40][41][42] |
Vibrio anguillarum |
Vibriosis |
Salmonids, turbot, sea bass, striped bass, eel, ayu, cod, and red sea bream |
[10][43][44] |
Vibrio salmonicida |
Vibriosis |
Atlantic salmon, cod |
[45][46][47] |
Vibrio carchariae |
Vibriosis, infectious gastroenteritis |
Shark, abalone, red drum, sea bream, sea bass, cobia, and flounder |
[48][49][50] |
Moritella viscosa |
Winter ulcer |
Atlantic salmon |
[51][52][53] |
Tenacibaculum maritimum |
Flexibacteriosis |
Turbot, salmonids, sole, sea bass, gilthead sea bream, red sea bream, and flounder |
[54][55][56] |
Lactococcus garvieae |
Streptococcosis or lactococcosis |
Yellowtail, rainbow trout, and eel |
[57][58][59][60] |
Streptococcus iniae |
Streptococcosis |
Adriatic sturgeon, rainbow trout |
[61][62][63] |
Streptococcus parauberis |
Streptococcosis |
Turbot |
[64][65][66] |
Streptococcus phocae |
Streptococcosis |
Atlantic salmon |
[67][68][69] |
Mycobacterium marinum |
Mycobacteriosis |
Sea bass, turbot, and Atlantic salmon |
[70][71][72] |
3. Fish Vaccines
Fish infections continue to be a serious economic issue in commercial aquaculture around the world, despite many initiatives to develop new therapies
[73]. Although antibiotics or chemotherapeutics may be used to treat fish disease, these are associated with obvious disadvantages such as drug resistance and safety concerns of consumers and the environment
[74]. Vaccination is an effective technique to prevent a large variety of bacterial and viral infections and contributes to the environmental, social, and economic sustainability of aquaculture production globally
[75]. Since the initial reports in the 1940s, several vaccines have been developed that have greatly reduced the impact of loss caused by bacterial and viral infections in fish
[76][77]. Millions of fish are currently vaccinated each year, and there has been a shift away from using various antibiotics and toward immunization in different parts of the world
[78].
A component either contained in or produced from the fish pathogen is used as an antigen to develop the vaccine
[75][79]. This component will be involved in the activation of the innate or adaptive immune responses of the fish in response to a specific microbial infection. Over 100,000 research reports on fish vaccine development have been published in the last two decades, as well as several reviews on the history, developments, types, and routes of administration, and the opportunities and challenges of producing fish vaccines have been studied elaborately
[80]. Many studies have summarized the importance of using adjuvants and immunostimulants in boosting the immune response of fish vaccinations, as well as delivery strategies
[81][82].
Several inactivated, live-attenuated, and DNA vaccines have been developed and are currently applied in large-scale fish farming operations. The first successful available commercial bacterial vaccine was developed against enteric redmouth disease and vibriosis and was introduced in the United States in the late 1970s. It was developed based on whole-cell inactivation and administrated through immersion methods
[83][84]. Since 1990 the global development of fish vaccines has followed a path similar to that of human and veterinary vaccines, with extensive interactions between research and development, pharmaceutical industries, and regulatory bodies of concerned geographical regions. The major fish vaccine producers include Novartis Animal Health (Switzerland), Intervet International (The Netherlands), Pharmaq (Norway), Bayer Animal Health (Bayotek)/Microtek, Inc. (Germany/Canada), and Schering-Plough Animal Health (USA). The global commercial market for these companies is dominated by salmon and trout aquaculture productions
[83].
There is a need for a comprehensive assessment of the current state of the fish vaccine sector due to the emergence of new vaccination technology developments. Over 26 licensed fish vaccines are available for use in a different range of fish species worldwide (
Table 2). Most of the developed vaccines have been licensed for use in a number of aquaculture species by the United States Department of Agriculture (USDA) and are mainly prepared using traditional production methods that involve the cultivation of specific targeted pathogens
[85][86]. According to the USDA, vaccines are currently provided to 77 types of fish against more than 22 types of different bacterial and six viral pathogenic specie
[87]. Various countries, including Japan and Korea, have licensed and commercialized their fish vaccines
[88][89]. In Japan, nine pharmaceutical industries produce fish vaccines for the Japanese market, with 29 vaccine formulations approved since 2018. Vaccines against eight bacterial species and two viral species have been approved and are in use for more than 13 types of fish species
[88]. In Korea, 29 vaccines for ten types of fish pathogens are approved and commercially available
[89].
Table 2. USDA Approved Bacterial Fish Vaccines.
Disease |
Pathogen |
Vaccine Type |
Delivery Methods |
Country/Region |
Make |
Vibriosis |
Vibrio anguillarum; Vibrio ordalii; Vibrio salmonicida |
Inactivated |
IP or IMM |
USA, Canada, Japan, Europe, Australia |
Merck Animal Health |
Furunculosis |
Aeromonas salmonicida, subsp. Salmonicida |
Inactivated |
IP or IMM |
USA, Canada, Chile, Europe, Australia |
MSD Animal Health |
Bacterial kidney disease (BKD) |
Renibacterium, salmoninarum |
Avirulent live culture |
IP |
Canada, Chile, USA |
Renogen |
Enteric septicemia of catfish (ESC) |
Edwarsiella ictaluri |
Inactivated |
IP |
Vietnam |
Pharmaq |
Columnaris disease |
Flavobacterium columnaris |
Attenuated |
IMM |
USA |
Merck Animal Health |
Pasteurellosis |
Pasteurella piscicida |
Inactivated |
IMM |
USA, Europe, Taiwan, Japan |
Pharmaq AS |
Lactococcosis |
Lactococcus garvieae |
Attenuated |
IP |
Spain |
hipara |
Streptococcus infections |
Streptococcus spp. |
Inactivated |
IP |
Taiwan Province of China, Japan, Brazil, Indonesia |
Aquavac-vaccines |
Salmonid rickettsial septicemia |
Piscirickettsia salmonis |
Inactivated |
IP |
Chile |
Pharmaq |
Motile Aeromonas septicemia (MAS) |
Aeromonas hydrophila, A. caviae, A. sobria |
Inactivated |
IP |
Asia, Europe, United States |
Pharmaq |
Wound Disease |
Moritella viscosa |
Inactivated |
IP |
Norway, UK, Ireland, Iceland |
Pharmaq |
Tenacibaculosis |
Tenacibaculum maritimum |
Inactivated |
IP |
Spain |
hipara |
Channel Catfish Septicemia |
Edwardsiella ictaluri |
Avirulent live culture |
IMM |
United States |
AquaVac |
Enteric Redmouth Disease |
Yersinia ruckeri |
Attenuated |
IMM |
United States |
Elanco (Aqua Health) |
4. Conclusions
Large-scale reductions in the usage of antibiotics were brought on by effective fish vaccinations. But combining all factors that interfere with development to a ministration method remains the real issue in the fish vaccine. Despite several positive results in research and experimental trials with a moderate to high market potential for fish vaccines, there are only a few approved vaccines available on the market to protect against diseases in economically important fish. However, with recent advancements, multiple next-generation vaccine developments can be achieved against various infectious pathogens, especially bacteria, with more clearly defined adjuvants, microcarriers, and nanocarrier-based precisely targeted vaccines to produce higher protective immunity in cultured fish species, which may be available soon for the aquaculture sector. Research on vaccine formulations comprising the most suitable antigenic components, as well as field trial studies that corroborate laboratory findings, will aid in the development of a fish vaccine that is effective against the majority of bacterial infections. This will contribute to the sustainable growth of the economy and control the impact of environmental pollution caused by conventional antibiotics and chemical-based treatments.