## 5 Current Licensed Vaccines for Viral Diseases
### Challenges and Limitations in Developing Vaccines for Fish  
The ideal vaccine provides long-term immunity, is easily distributed and is economical. Oral vaccination is the preferred method of administration due to its versatility and ease of use, it does not cause stress to fish, and it can be distributed in large numbers at once. However, as much as oral vaccination is considered a future prospect, it comes with its limitations. Due to its route of entry, this form of vaccination can cause oral tolerance. Defined as the suppression of humoral and cellular immune responses, oral tolerance is one of the main issues that hinder the development of effective oral vaccines [29]. Though there is some information regarding the mechanism responsible for this phenomenon in mammals and humans, there is little information on how it works in fish [165; 166]. Similar to oral vaccines, mucosal vaccines are widely distributed, easy to administer, and can provide optimal administration efficacy as fish have large mucosal surfaces [1]. The issue in this case involves efficacy. There are no immunostimulants in non-replicating mucosal vaccines that can impact the vaccine's performance and there is also the risk of prolonged exposure to vaccination [167]. Because most mucosal vaccinations utilize bath administration, it can be difficult to calculate how much of the antigen was administered in relation to the functional testing of mucosal T cells, which can prevent a proper evaluation of vaccination efficacy [168]. Bath immersion involves the administration of vaccine antigens via immersive techniques [72]. Immersion vaccines facilitate mass vaccination and can provide vaccination to smaller fish that are not able to endure intraperitoneal vaccination. Though new research has found that live attenuated vaccines, recombinant vaccines and chitosan-based vaccines increase immersion vaccine efficacy, it is difficult to produce a bath administration vaccine in the lab due to the denaturation of antigens when crossing digestive and mucosal barriers, variability in results, and difficulty in determining improvement measures from experimental trials [1; 22; 169; 170]. Although such vaccine models have the potential to be successful, there needs to be more research conducted on immunological mechanisms to understand how to formulate a vaccine that will be able to successfully produce the desired result without severe side-effects, such as chronic stress. Researchers should focus on producing vaccines that induce long-term immunity. This way, fish do not have to repeatedly undergo handling and anesthetic procedures, which are necessary for injection-based vaccines administration [171]. This would also reduce susceptibility to oral tolerance. When discussing administration methods, bath and immersion vaccines are also noted. Bath vaccination is noted as inducing long-term immunity. Although such limitations are directly related to vaccine formulation and administration, certain factors such as cost efficiency are indirectly related. As much as cost efficiency is one of the strengths of vaccination, a lot of money is needed to produce a strong vaccine. From antigen isolation to producing the most favorable adjuvant and evaluating the mortality of the vaccine in a commercial setting, there are several steps required for the production of a strong vaccine, all of which can be costly. There should also be more information on the efficacy of commercial vaccines. Although there are certain regulations and standards that a certified vaccination must meet to become commercially available, there are not many scientific papers comparing the efficacy of different vaccines that claim to protect against the same pathogen. This would aid farmers in determining which vaccine is best for them to use. Though vaccines have the ability to prevent viral outbreaks, they cannot be used on fish weighing less than 20 g [171]. Many of these fish are in the larval or fry stage.