The intensification of global aquaculture faces the constant challenge of disease outbreaks, which cause significant economic losses each year. Vaccines are a key tool for enhancing the immunity of aquatic animals and preventing large-scale diseases, reducing the reliance on chemicals. In this context, a promising technology is emerging: microalgae-based vaccines, which offer a sustainable and effective solution for immunization in aquaculture.
A team of researchers from South China University of Technology and Imperial College London published a study in the journal Trends in Biotechnology exploring vaccine antigen design, oral delivery, and the immune benefits of microalgae. The researchers expect that advances in synthetic biology and fish immune metabolism will drive future innovations.
Why Use Microalgae to Produce Vaccines?
Microalgae are positioning themselves as an advantageous platform for producing recombinant antigens (the molecules that trigger the immune response) specific to fish and other aquatic organisms. Their benefits over traditional systems (bacteria, yeast, mammalian cells) are notable:
- Sustainability: Their cultivation uses photosynthesis as the primary energy source and does not require complex infrastructure, reducing the carbon footprint. Furthermore, they are biodegradable, minimizing environmental impact.
- Efficient Cultivation: They can grow relatively quickly and be cultivated on a large scale at low cost, in both open and closed systems, which minimizes contamination risks.
- Genetic Engineering: It is possible to genetically modify microalgae to produce the antigens of interest by integrating the necessary genes into their nuclear or chloroplast genome.
- Dual Benefit: Vaccine and Nutrition: Microalgae not only deliver the vaccine but are also a valuable nutritional source for aquatic animals.
The Revolution of Microalgae-Based Oral Vaccines
One of the great advantages of using microalgae is the possibility of developing oral vaccines. This means animals can be vaccinated simply by ingesting the modified microalgae, eliminating the need for injections (which are stressful and laborious) and costly antigen purification processes.
How Do They Work?
- Antigen Protection: The microalga’s cell wall protects the antigen during its passage through the fish or shrimp’s gastrointestinal tract.
- Release and Absorption: Once in the intestine, the microalgae are digested, releasing the antigens. These interact with the intestinal mucosa, where specialized immune cells (like M cells and dendritic cells) recognize and capture them.
- Immune Activation: The microalga’s own surface, rich in bioactive compounds such as polysaccharides and glycoproteins, acts as a natural adjuvant, enhancing the immune response. This activates both local immunity in the mucosa and systemic immunity throughout the organism.
- Immunological Memory: Microalgae facilitate the activation of B cells (antibody producers) and T cells, generating long-lasting immunological memory. If the animal is later exposed to the actual pathogen, its immune system will respond quickly and effectively.
Improving Efficacy
To further optimize these vaccines, strategies being explored include:
- Protective Encapsulation: Coating the microalgae with materials like alginate or chitosan can improve antigen stability and ensure its release at the appropriate site in the intestine.
- Co-expressed Adjuvants: Designing microalgae that produce not only the antigen but also immunostimulatory molecules (adjuvants) has been shown to generate superior immune responses.
Rational Antigen Design: The Key to Success
The effectiveness of any vaccine lies in the antigen design. Current research relies on advanced computational tools (such as artificial intelligence and machine learning) for rational design. This allows for:
- Optimizing the immunological efficacy of the antigen.
- Designing chimeric antigens that offer protection against multiple pathogens (multivalent vaccines).
- Predicting and improving antigen stability.
- Analyzing compatibility with adjuvants.
- Accelerating the discovery and optimization of new antigens through data-driven approaches.
Evidence of Success: Practical Cases
Research has already demonstrated the efficacy of these vaccines in aquaculture:
- Shrimp vs. WSSV: Microalgae (Chlorella vulgaris and Chlamydomonas reinhardtii) modified to express the VP28 protein of the White Spot Syndrome Virus (WSSV) significantly increased the survival rate of shrimp after infection, via oral administration.
- Grouper vs. VNN: An oral vaccine based on Chlamydomonas reinhardtii expressing the viral coat protein of the Nervous Necrosis Virus (VNN) improved grouper survival and showed positive effects on immune indicators like IgM and cytokines.
- Zebrafish / Koi Carp: Transgenic Schizochytrium sp., used as an oral vaccine, activated specific immune responses in the gut.
Challenges and Future Perspectives
Despite the great potential, scientists highlight that challenges still need to be overcome:
- Improving the efficiency and stability of genetic tools for modifying microalgae.
- Developing efficient bioreactors for large-scale cultivation.
- Ensuring antigen stability and quality in the animal’s intestinal environment.
- Addressing regulatory complexities and biosafety concerns associated with the use of genetically modified organisms (GMOs) in aquaculture.
- Deepening the understanding of the specific immune responses generated by these vaccines in different aquatic species.
The future is promising. The combination of advances in synthetic biology, bioengineering, artificial intelligence, and greater knowledge of fish immune metabolism will drive innovation. Next-generation microalgae vaccines are expected to be even more specific, potent, long-lasting, safe, and capable of offering broad-spectrum protection, adapting rapidly to new emerging pathogens.
Conclusion
Oral vaccines based on microalgae represent a significant step towards more sustainable and resilient aquaculture. By combining efficient antigen production, ease of oral administration, nutritional benefits, and intrinsic immunostimulatory properties, this technology offers a powerful tool to protect the health of fish and shrimp, reducing economic losses and the environmental impact associated with disease control. Continued research and development in this field will undoubtedly open new doors to improve aquaculture health globally.
Contacto
Haohong Chen
School of Food Science and Engineering, South China University of Technology
Guangzhou, 510640, China
Email: haohongchen0@scut.edu.cn
Referencia
Chen, H., Jiang, J., & Ledesma-Amaro, R. (2025). Microalgae-based vaccines for aquaculture. Trends in Biotechnology. https://doi.org/10.1016/j.tibtech.2025.04.001
Editor at the digital magazine AquaHoy. He holds a degree in Aquaculture Biology from the National University of Santa (UNS) and a Master’s degree in Science and Innovation Management from the Polytechnic University of Valencia, with postgraduate diplomas in Business Innovation and Innovation Management. He possesses extensive experience in the aquaculture and fisheries sector, having led the Fisheries Innovation Unit of the National Program for Innovation in Fisheries and Aquaculture (PNIPA). He has served as a senior consultant in technology watch, an innovation project formulator and advisor, and a lecturer at UNS. He is a member of the Peruvian College of Biologists and was recognized by the World Aquaculture Society (WAS) in 2016 for his contribution to aquaculture.
