Next-Generation Fish Vaccines: DNA, Subunit and Recombinant Approaches

What happens when conventional whole-pathogen vaccines are not enough? 

The development of fish vaccines is moving beyond traditional killed preparations towards approaches that can identify and target specific antigenic components. Advances in molecular biology, biotechnology and reverse vaccinology have enabled the development of subunit, plasmid DNA, recombinant live-vector and recombinant protein vaccines, several of which have been experimentally evaluated in fish^[1]. 

For veterinarians involved in aquatic animal health, these approaches are important because many bacterial diseases still lack effective vaccines despite the availability of several commercial products^[2]. 

From whole pathogens to selected antigens 

Traditional fish vaccines have often relied on killed pathogens. Newer approaches can instead focus on components associated with the pathogen and capable of stimulating an immune response. 

Reverse vaccinology is one such approach. Rather than relying only on conventional vaccine development, it can be used to identify potentially useful antigenic targets. In largemouth bass (Micropterus salmoides), reverse vaccinology was used to identify potent antigenic targets for subunit vaccines against fish nocardiosis. The resulting vaccines were reported as promising for nocardial prophylaxis, although their effects differed between vaccine approaches^[2]. 

The clinical relevance is straightforward: Antigen selection becomes a central consideration when developing targeted vaccines for pathogens for which effective protection remains difficult to achieve. 

DNA vaccines: Targeting specific bacterial disease 

Plasmid DNA vaccination represents another next-generation approach described in fish. 

A SagH gene-based DNA vaccine targeting Streptococcus iniae produced a relative percent survival (RPS) of 92.62% at one month and 90.58% at two months following vaccination against S. iniae serotype I. The same vaccine also demonstrated cross-protection against serotype II, with RPS values of 83.01% and 80.65% at one and two months, respectively^[2]. 

These findings illustrate why antigen-specific approaches are being explored: protection may extend beyond the particular challenge used to evaluate the vaccine. However, these reported outcomes should be interpreted within the experimental conditions described rather than treated as universal field performance. 

Recombinant vaccines and immune responses 

Recombinant approaches have also been investigated against bacterial infections. 

An inactivated recombinant vaccine encoding a cell-wall surface-anchored family protein of Streptococcus agalactiae was administered to red hybrid tilapia (Oreochromis sp.). Orally inoculated fish showed strong IgM responses in serum, mucus, and gut lavage fluid, with a reported RPS of 70%^[3]. 

Another example involved a multicomponent vaccine designed to protect trout against yersiniosis, furunculosis and vibriosis. It induced specific antibody responses to different bacterial antigens and regulated expression of genes involved in the immune response under the experimental conditions described^[2]. 

What does this mean for aquatic veterinary practice? 

The important point is not that newer platforms automatically replace conventional vaccines. Rather, they expand the approaches available for addressing pathogens where existing protection remains inadequate. 

The development pathway is also becoming more targeted. Antigenic components, adjuvants, microcarriers, and nanocarrier-based delivery systems are identified as areas with potential to produce more precisely targeted immune responses in cultured fish. 

Field validation remains particularly important. Field trials that corroborate laboratory findings, along with vaccine formulations containing appropriate antigenic components, are important for advancing these approaches towards practical application. 

Clinical Bottom Line 

Next-generation fish vaccines offer more targeted approaches to disease prevention by focusing on specific antigenic components and molecular vaccine platforms. DNA, subunit, and recombinant vaccines have shown promising immune responses and protection against selected bacterial pathogens, but their practical value depends on appropriate antigen selection, formulation, delivery, and validation under field conditions.

References:

1. Mzula A, Wambura PN, Mdegela RH, Shirima GM. Current state of modern biotechnological‐based Aeromonas hydrophila vaccines for aquaculture: A systematic review. BioMed research international. 2019;2019(1):3768948. https://onlinelibrary.wiley.com/doi/pdf/10.1155/2019/3768948
2. Irshath AA, Rajan AP, Vimal S, Prabhakaran VS, Ganesan R. Bacterial pathogenesis in various fish diseases: recent advances and specific challenges in vaccine development. Vaccines. 2023 Feb 17;11(2):470. https://www.mdpi.com/2076-393X/11/2/470
3. Bøgwald J, Dalmo RA. Protection of teleost fish against infectious diseases through oral administration of vaccines: update 2021. International Journal of Molecular Sciences. 2021 Oct 10;22(20):10932. https://www.mdpi.com/1422-0067/22/20/10932