Vaccine:�It’s Uses and Advantages & Disadvantages.

Therapeutics and Heath Management In Aquaculture: AQC:507

A vaccine is a biological preparation that improves immunity to a particular disease. A vaccine typically contains an agent that resembles a disease-causing microorganism, and is often made from weakened or killed forms the microbe. The agent stimulates the body’s immune system to recognize the agent as foreign, destroy it, and “remember” it, so that the immune system can more easily recognize and destroy any of these microorganisms that it later encounters in future.

Aquaculture continues to expand, disease problems will increase. Therefore, disease research and the implementation of new disease control concepts are important to maintain sustainability.
The development of an effective vaccine is a complex process. One of the prerequisites understanding of basic epidemiology of diseases and the immune system of the target species is required.
The importance of disease control is increasingly recognized by both farmers and governments due to the significant economic losses caused by diseases and international pressure on the use of chemicals and antibiotics.
A number of vaccines have been in used by the salmonid industry for decades, however, commercial vaccine development for other aquaculture sectors, including warm water fish, is still quite limited.

1. vaccine : It’s Uses and Advantages & Disadvantages. Submitted to Prof T.K Ghosh Dept of Aquaculture F.F.Sc ,WBUAFS Presented by Haladhar Hembram M.F.Sc 1 st Year Dept of Aquaculture Therapeutics and Heath Management In Aquaculture: AQC:507

2. Introduction Vaccination is a pivotal tool in disease control. Edward jenner's 1798 work on smallpox marked the inception of vaccination , and he coined the term ' vaccine .' Building on this foundation, Pasteur extended the application of vaccination to combat various infectious diseases, including anthrax, rabies, and chicken cholera. Vaccination induces active immunity by using killed or weakened bacteria. The immune system recognizes these agents, initiating antibody production and establishing a defense mechanism against potential infections. Vaccination, a preventive measure, offers distinct advantages over chemotherapeutic approaches. Its routine use in aquaculture, especially in intensive systems, significantly enhances disease protection, reinforcing its pivotal role in promoting health and sustainability. The first report on fish vaccination was done by David C. B. Duff and he is regarded as a “Father of fish vaccination”.

3. Definition A vaccine is a biological preparation that improves immunity to a particular disease. A vaccine typically contains an agent that resembles a disease-causing microorganism, and is often made from weakened or killed forms the microbe. The agent stimulates the body’s immune system to recognize the agent as foreign, destroy it, and “remember” it, so that the immune system can more easily recognize and destroy any of these microorganisms that it later encounters in future.

4. TYPES OF VACCINES On the basis of inducing agent and preparation method vaccines are can be classified as- Whole-organism vaccines Killed Attenuated Purified macromolecules as vaccines Toxoids Subunit vaccines/conjugate vaccine Recombinant DNA-based vaccines

5. Killed Or Inactivated Vaccine These vaccines contains killed, but previously virulent, micro-organisms that have been destroyed with chemicals, heat, radioactivity or antibiotics. Inactivated vaccines prepared by physical or chemical treatment. Pathogens become inactive but maintain immunogenicity. Used when attenuated vaccines are unavailable or during outbreaks. Chemical inactivating agents: formaldehyde, glutaraldehyde, beta propiolactone. Physical inactivating agents: gamma irradiation, u-v irradiation. Inactivated vaccines often require adjuvants for increased potency. Killed vaccines have been developed for some pathogenic fish viruses such as Infectious Pancreatic Necrosis Virus (IPNV), Infectious Haematopoietic Necrosis Virus (IHNV), Viral Haemorrhagic Septicaemia Virus (VHSV) and Spring Viremia Of Carp Virus (SVCV).

6. Advantages– No possibility of reversion. No shedding and contamination of environment. Quite stable, thus less need for cold chain. More immunogenic. Whole organism has both T and B epitope. Disadvantages– Cannot replicate so antigen is limited. Require, multiple doses, adjuvants vaccination and boosters. If not properly inactivated, it may cause disease outbreaks. Increased risk of allergic reactions due to large amounts of antigen involved. Costly May be ineffective against intracellular organisms.

7. Live attenuated vaccines These vaccines contains live, attenuated microorganisms. Many of these are live microorganisms that have been cultivated under conditions that disable their virulent properties or which use closely related but less dangerous organisms to produce a broad immune response. Virulence reduction and immunogenicity maintenance achieved through adaptation in unfavorable conditions. Attenuation methods: growth in unnatural host, passaging in non-homologous host or conditions, cold adaptation. Cold adaption involves adapting the virus to grow at lower temperatures. Thermo-stable vaccine strains grow at elevated temperatures. Temperature-sensitive mutants cannot grow at slightly elevated temperatures. Attenuation is the process of reducing virulence while retaining immunogenicity. A koi herpesvirus vaccine based on an attenuated strain of carp interstitial nephritis and gill necrosis virus is available in Israel.

8. Advantages– Replication provides large quantities of immunogen. There is no need for adjuvant. Single dose often produce long lasting immunity Whole organism has both T and B epitopes The vaccine is cost effective and often does not require booster vaccination Can be effective against intracellular pathogens Disadvantages– Chance of reversion to virulence There may be shedding of virus Can induce transient immunosuppression Cold chain required for transport Possible contamination with other animal viruses There may be side effects due to unwanted parts of the vaccines

9. Toxoid Both gram negative and gram-positive bacteria produce exotoxins. Exotoxins can be inactivated by formaldehyde, iodine, other chemical or heat treatment & form toxoid. Toxoid is immunogenic without toxic effects. Toxoid vaccines have been used for tetanus, anthrax etc. Some veterinary vaccines combine both toxoid and killed bacteria by formalinizing whole culture and this is called anaculture . these types of vaccines are available for clostridial diseases. Trypsinization of anaculture makes it more immunogenic. Advantage : The exotoxin is immunogenic and whole organism can be avoided. Disadvantage : Only effective if diseases caused solely by bacterial exotoxins.

10. Subunit vaccines/conjugate vaccines It is possible to identify the peptide sites encompassing the major antigenic sites of viral antigens , from which highly purified subunit vaccines can be produced. But increasing purification may lead to loss of immunogenicity, and this may necessitate coupling to an immunogenic carrier protein or adjuvant. Example of a purified subunit vaccine is HA vaccines for influenza a and b. Bacterial capsular polysaccharides are immunogenic but incapable of evoking T cell responses. Vaccines efficacy can be greatly increased by conjugating the capsular polysaccharide to a protein carrier capable of supply of t cell epitopes called a conjugate vaccine. Infectious Salmon Anaemia Virus (ISAV) vaccine : this vaccine contains a recombinant protein that is derived from the ISAV hemagglutinin-esterase protein.

11. Advantages– Avoids use of whole organism. Side effects due to undesired part of the organism is reduced. Supplies multiple epitopes. Disadvantages– Possible alteration of pathogen protein conformation during purification may decreases immunogenicity. Can be labored intensive and costly to purify immunogens. May require cold chain– sometimes too large to fit into the vaccine delivery systems.

12. Recombinant DNA-based vaccines DNA vaccines components: origin of replication, antibiotic-resistant gene, enhancer/promoter, mRNA termination/polyadenylation sequence. Constructed plasmids grown in e. Coli, purified, suspended in saline, and introduced into the host via intramuscular injection or gene gun. Used in fish with promising results. Intramuscular injection of plasmid constructs in rainbow trout leads to strong expression of reporter genes. Luciferase gene injection in rainbow trout shows maximum activity at 5 to 7 days post-injection, remaining active for 115 days.

13. Combined injection of plasmids carrying VHSV and IHNV glycoprotein genes results in plasmid DNA persistence in muscle cells for up to 45 days. DNA immunization induces specific and non-specific immune responses in the host. High-level protection observed in clinical animal models with specific antibodies and t-cell responses. Significant protection in rainbow trout against IHNV challenge following injection of construct encoding IHNV glycoprotein. DNA vaccines can introduce genes for antibodies targeting and destroying pathogens. DNA vaccines overcome many drawbacks of other vaccine types.

14. Advantages of DNA vaccines: Induce production of native protein with proper post-translational modifications. Capable of inducing a long-lasting immune response. Economical and safe. Practical application in fish faces challenges due to: Most fish pathogens, especially viruses, affect fish at a very young age. Difficulty in administering vaccines to small fish through injection. Injection method useful for immunizing broodstocks of large fish to passively transfer immunity to offspring (demonstrated in controlling ich). Challenging to use DNA vaccines for individual fish on a large scale in intensive aquaculture unless orally or gill filament administration methods are developed.

15. Vaccine delivery Vaccines are delivered to fish either by mouth, immersion or injection. Each approach has advantages and disadvantages. The most effective way to deliver fish vaccine depends on the pathogen and its natural route of infection, the life stage of the fish, production techniques and other logistical considerations. A specific route of administration or even multiple routes may be necessary for adequate protection.

16. Oral vaccination In oral vaccination, the vaccine is either mixed with the feed, coated on top of the feed (top dressed) or bio-encapsulated Bio-encapsulation is used where fish or shrimp fry are to be vaccinated. In this case, live feed such as artemia nauplii, copepods or rotifers are incubated in a vaccine suspension and then fed to the fry. Since these live organisms are non-selective filter feeders, they will accumulate the antigen in their digestive tract and, as such, transform themselves into living microcapsules.

17. Immersion vaccination (A) Dip vaccination (B) Bath vaccination In dip vaccination, fish are immersed for a short duration, usually 30-60 sec, in a highly concentrated vaccine solution. In bath vaccination, fish are exposed for a longer time, usually one to several hrs, in a lower concentration of antigen. Immersion vaccination is widely used for fry. It is an effective method that results in relatively good protection for a significant period of time.

18. Injection vaccination Injection delivery system is an effective way of inducing antibody response in fish. The injection may be intraperitoneal or intramuscular. Injection is in general superior to any other vaccine application method because it is directly incorporate vaccine in the body. But main disadvantage is it may cause stress and inflammatory reactions.

19. Vaccine Advantage Disadvantage Oral The easiest method because feeding is a normal part of production. A coating agent is often needed to avoid breakdown in fish digestive system. Oral Stress on fish is minimal. Conveys relatively short immunity, may require additional vaccination. Immersion Relatively easy to perform with minimal interruption to production schedule. Smaller, younger fish may have immature immune systems that require a second vaccination. Immersion Stress on fish is minimal. May not convey protection as effective as injection for some pathogens. Injection Effective for many disease pathogens. Requires more time and skilled personnel. Injection Much longer protection duration. Fish under 10 g may not respond well. Injection Every fish is treated, providing more assurance to the producer. Causes the most stress on fish.

20. VACCINES SPECIES DISEASE PICTURE Aeromonas salmonicida Bacterin Atlantic salmon Furunculosis Vibrio anguillarum . V. Ordalii Bacterin Rainbow trout Vibriosis Yersinia ruckeri Bacterin Salmonids Yersiniosis (enteric red- mouth disease) Vibrio salmonicida Bacterin Salmonids Vibriosis Vibrio anguillarum-salmonicida Bacterin Salmonids Vibriosis Edwardsiella ictaluri Bacterin Salmonids Furunculosis Spring viraemia of carp virus Catfish Enteric septicaemia Koi herpes virus (KHV) Common carp Spring viraemia of carp virus Biofilm and free-cell vaccines of Aeromonas hydrophila Koi carp Koi herpes virus (KHV) disease

21. Potential Benefit Of Vaccine Increased appetite and growth in vaccinated fish compared to non- vaccinated fish is more because of the better food conversion rates in vaccinated fish. Potential of growing vaccinated fish at higher densities because disease is not a limiting factor in the population. Immunization of pre-spawning females may have potential as a means of protecting fish against pathogens which affect the early life stages, such as Flavobacterium psychrophilum , Edwardsville ictaluri . Reduction of drug use and therefore, the no appearance of bacterial drug resistance, as well as drug residues in the final product. Improvement of industry image for the sanitary quality of the fish produced, as well as from the environmental safety stand point of view.

22. Risk associated The primary risk associated with vaccines, especially vaccines that utilize live organisms and vaccine itself may causes illness. Vaccine may behave as a super antigen and over stimulate the immune system. Some individuals may have an allergic reaction to the vaccine. Poor delivery technique may cause stresses which can result tissue damage, necrosis, infection or internal organ damage and death. Decrease in growth caused by side effects such as those produced by some adjuvant vaccines. Fish are weakened by improper handling or rearing practices.

23. Conclusion Aquaculture continues to expand, disease problems will increase. Therefore, disease research and the implementation of new disease control concepts are important to maintain sustainability. The development of an effective vaccine is a complex process. One of the prerequisites understanding of basic epidemiology of diseases and the immune system of the target species is required. The importance of disease control is increasingly recognized by both farmers and governments due to the significant economic losses caused by diseases and international pressure on the use of chemicals and antibiotics. A number of vaccines have been in used by the salmonid industry for decades, however, commercial vaccine development for other aquaculture sectors, including warm water fish, is still quite limited.