By Ubolsree Leartsakulpanich, Warangkhana Songsungthong, Wananit Wimuttisuk, Udom Sae-Ueng, Pinpunya Riangrungroj, and Kallaya Sritunyalucksana
Today, farmed shrimp account for more than half of the global shrimp consumption. In 2024, the value of the shrimp market was estimated at USD 75 billion and was expected to reach USD 102.48 billion by 2033 (Grand View Research).
At the global level, it is an important sector contributing to food security and economic growth. At the local level, for farmers, a healthy shrimp stock is the key to gainful and sustainable shrimp production. Nonetheless, the sustainability of shrimp farming is often disrupted by disease outbreaks, such as vibriosis caused by four major pathogenic Vibrio spp.: V. parahaemolyticus, V. alginolyticus, V. harveyi, and V. vulnificus. Although these bacterial infection can be suppressed by antibiotics, the shift toward a more appropriate usage of antibiotics to mitigate the risks posed by antimicrobial resistance (AMR) has spurred the development of antimicrobial alternatives to control disease outbreaks and thus ensure sustainable aquaculture.
ShrimpGuard: Research and Product Development
To protect shrimp from vibriosis in hatchery settings, our team recently proposed to formulate and investigate an antimicrobial alternative that combined a phage cocktail with the three immune enhancers: universal Vibrio antigens, beta-glucan (Uengwetwanit 2025), and eLysozyme (Woraprayote 2020). Each component of ShrimpGuard will be discussed in more detail to provide the background and rationale for the product’s development.
Phage and Phage Cocktail
Bacteriophages or phages are viruses that specifically infect and kill bacteria. Phages were discovered independently by Frederick Twort in 1915 and Felix d’ Herelle in 1917 (Twort 1915; Fruciano 2007; Aswani 2021). D’Herelle coined the term bacteriophage, which means bacteria-eater virus, and introduced the phage therapy concept.
Many studies have reported the effectiveness of phage treatments to protect shrimp from Vibrio infections and reduce shrimp mortality (Jun 2018; Thammatinna 2023; Ngoc 2024). Phages are therefore attractive alternatives to traditional antibiotics for various applications, such as in food safety and aquaculture biocontrol. Because the mechanism of action of phages differs from that of antibiotics, phages can be an effective tool in the fight against antimicrobial resistant bacteria.
Unlike antibiotics which have broad spectrum activity, phages act only on the target bacteria. Other beneficial bacteria are not perturbed. If a broader spectrum is needed, a phage cocktail that combines phages with different specificities can be designed (Stalin 2017; Thammatinna 2023). In our study, the research team aims to formulate a phage cocktail that is effective against the four major Vibrio spp. responsible for vibriosis in shrimp.
Immune Enhancers
Immune enhancers are designed to stimulate animal hosts’ immune defense, thereby improving overall health and reducing disease severity. For ShrimpGuard, both specific- and non-specific immune enhancers have been explored for their efficacies in protecting shrimp against vibriosis.
Universal Vibrio Antigens
Universal Vibrio antigens are immune enhancers expected to provide protection against specific target pathogens, whereas eLysozyme and beta-glucan are considered broader spectrum immune enhancers.
Although shrimp lack a classical mammalian-like adaptive immune system (with B and T cells), recent evidence shows that specificity can be achieved, possibly through pattern-recognition molecules like Down Syndrome Cell Adhesion Molecule (DSCAM), lectins, and fibrinogen related proteins (FREP).
It has been observed that shrimp primed with inactivated pathogen or pathogen-derived molecules are better protected upon secondary exposure to the same pathogen (Lin 2013; Amatul-Samahah 2020; Yang 2021).
The immune priming concept therefore opens a possibility of using a “vaccine” to protect against vibriosis. Commonly used inactivated whole cell bacterial vaccines, despite being highly effective, protect only against the specific strains/serovars used in the formulation, which limits their practicality. To broaden the protection achieved by such a vaccine, the team proposed using universal antigens: antigens common across pathogenic Vibrio species and strains to prime shrimp immunity.
After analyzing hundreds of Vibrio genomes using an in-house algorithm, the team successfully identified universal antigen candidates. These purified candidates are being tested for immune stimulation and protection against vibriosis. Immune stimulation in shrimp after “vaccination” has been evaluated by various approaches such as phagocytic activity assay, phenoloxidase activity assay, and immune gene expression analysis.
ELysozyme
ELysozyme or enhanced lysozyme, derived from chicken egg white lysozyme, possesses antibacterial activity against both Gram-positive and Gram-negative bacteria, including the four Vibrio spp. responsible for vibriosis (Woraprayote 2020). In comparison to shrimp fed a normal feed, shrimp fed an eLysozyme-supplemented diet revealed reductions of Vibrio counts in the intestine and higher expression levels of immune- and antioxidant-related genes.
Beta-glucan
Beta-glucan is a glucose polymer which is obtained from various sources such as oats, barley, yeast, fungi, bacteria, and algae (Jayachandran 2018; Han 2020). Diverse sources and structures of beta-glucan, including those derived from the insect fungus Ophiocordyceps dipterigena BCC 2073, were examined for their immune-enhancing property. A trial using the O. dipterigena-derived beta-glucan in shrimp diets showed elevated expression levels of immune-related genes and immune supporting metabolites, as well as increased survival rates upon exposure to V. harveyi (Uengwetwanit 2025). The results thus indicated the potential of beta-glucan as a feed additive to promote shrimp health.
Benefits of ShrimpGuard
As ShrimpGuard is composed of various components with different actions, such as killing pathogens and boosting immune defense, the successful application of ShrimpGuard is expected to reduce shrimp mortality, lead to higher shrimp production and income for both farm owners and workers, thereby contributing to greater economic growth. In addition, the reduction of antibiotic use will lower the risk of antimicrobial residues in aquaculture products and the environment, minimizing the emergence and spread of AMR. This will ultimately result in safer aquaculture products and more sustainable aquaculture practice.
Possible Limitations of ShrimpGuard
Phages and universal antigens are biological agents that are sensitive to environmental factors, such as very low or high pH as well as drastic changes in temperatures. This concern can be addressed through screening for robust phages that tolerate aquaculture’s harsh environments. The research project will also explore nanoencapsulation as a means to improve phage and antigen stabilities during storage and delivery.
It should be mentioned that the use of phages as a biocontrol agent in aquaculture is still at an early stage, focusing on isolation, characterization, and laboratory scale efficacy studies. Furthermore, phage use for aquaculture is not yet approved in many countries, including Thailand. The research team is working hand-in-hand with regulatory bodies on safety assessments to make the ShrimpGuard application available in the near future.
Emergences of phage-resistant bacteria have been reported. Therefore, phage-resistant Vibrio may emerge following ShrimpGuard field application, possibly limiting ShrimpGuard potency in the future. This highlights the importance of using phage cocktails to delay resistance and the need to continuously identify new phages. Nonetheless, in addition to a phage cocktail, ShrimpGuard contains three immune enhancers that should alleviate the resistance problem.
Recommendations
Sustainability of shrimp aquaculture requires coordinated and cooperative actions from all stakeholders.
Shrimp farmers can adopt various approaches to improve disease control. Integration of antibiotic alternatives such as ShrimpGuard into their practices can provide protection against disease and reduce antibiotic dependence.
Researchers and academic institutions can accelerate antibiotic alternative innovations by developing new tools such as new standardized phage screening protocols and new artificial intelligence (AI) tools for phage selection. Standardizing phage screening methods and optimizing bacterial host range testing protocols are recommended so that the results from various laboratories can be compared.
With the advancement of AI, computational tools can be leveraged to speed up phage screening, host range determination, and cocktail formulation. Additionally, understanding the synergistic mechanisms at play between phage and immune enhancers will allow further development of more effective formulations. Field trials under varied farming conditions will ease the transfer of laboratory findings into practical solutions.
Government and regulatory bodies can accelerate the transition to antibiotic-free farming. Raising awareness about antimicrobial resistance within aquaculture sectors can promote the shift toward safer antibiotic alternatives. Developing clear guidelines for standards and approval pathways for new antibiotic alternatives, including safety evaluations and quality controls, will ensure the prudent and effective use of these tools.
Private sector investment in the production of stable antibiotic alternative formulations and affordable feed additives will ensure that the innovations reach shrimp farmers at all scales.
Through close collaboration among all stakeholders, it will be possible to maintain a healthy shrimp stock with less dependence on antibiotics and limit the emergence and spread of antibiotic resistant bacteria. Ultimately, the goal of sustainable aquaculture production, for improved food security and food safety, will be achieved.
Social Considerations
While aiming to achieve sustainable aquaculture, the ShrimpGuard project also takes gender equality and social inclusion into account. In the aquaculture industry, women and foreign workers are often responsible for routine farm chores ranging from feed preparation to product harvesting.
Enabling women and foreign workers through inclusive training programs with flexible schedules offered in wide delivery locations and in multilingual documentation will enhance ShrimpGuard’s success. In addition, engaging local communities through participatory workshops and demonstration trials will allow underrepresented groups to voice their needs and feedback, ensuring that technology design and deployment are responsive to their realities.
Conclusion
Vibriosis is a major threat to shrimp farming. Implementing various preventive measures and integrating new antibiotic alternatives like ShrimpGuard will minimize the dependence on antibiotics as well as mitigate the risk posed by antimicrobial resistant bacteria. Due to the multiple simultaneous modes of action derived from bacteriophages and immune enhancers, ShrimpGuard is expected to offer a sustainable and eco-friendly alternative to antibiotics.
Acknowledgements
The ShrimpGuard project was carried out with financial support from the International Development Research Centre (IDRC), Canada, and the Global AMR Innovation Fund (GAMRIF), part of the UK Government’s Department of Health and Social Care (DHSC).
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