Chilean scientists take different path to vaccine discovery

Following the first step taken by Chilean scientists in designing a new vaccine against bacterial kidney disease (BKD), the project is beginning to reveal its true potential: a next-generation strategy based on reverse vaccinology that could change the way complex pathogens are dealt with in salmon farming.

In an interview with Fish Farming Expert’s Chilean sister site Salmonexpert.cl, Dr Fernando Gómez, a researcher at the Pontifical Catholic University of Valparaíso (PUCV) and a member of the development team, delves into the scope of this innovative approach, which focuses on a chimeric protein designed from the complete analysis of the genome of Renibacterium salmoninarum, the bacterium which causes BKD.

Antibody production and activation of cellular immune response

One of the main changes introduced by this technology is the shift from traditional methods towards a rational design of vaccines.

“For many years, vaccine development was based on cultivating the microorganism, inactivating or attenuating it, and evaluating whether it provided protection. Today we can do the reverse: first identify the proteins with the greatest immunological potential and then design the vaccine candidate,” explains Gómez.

This approach, known as reverse vaccinology, allows for the analysis of thousands of proteins instead of working with a few empirically selected ones. The main advantage is that it enables a much more rational selection of antigens, reducing time and costs while increasing the likelihood of success.

Unlike conventional strategies, the Chilean development does not target a single objective, but rather multiple key mechanisms of the bacteria.

“We were interested in proteins that were conserved across different strains of R. salmoninarum, that were recognisable by the immune system, and, above all, that participated in processes essential for the bacteria. In this way, we reduced thousands of proteins to a much smaller group of truly interesting candidates. Finally, the vaccine was composed of protein fragments that participate in very different functions that the bacteria need to survive and establish infection,” the researcher explains.

These targets include essential processes such as iron acquisition, interaction with host cells, nutrient transport, and molecule secretion.

Thus, the idea was to enable the fish to simultaneously recognise several important mechanisms for the pathogen, instead of concentrating the response on a single target.

“Furthermore, during the design process, we not only looked for proteins capable of stimulating antibody production, but also for regions with the potential to activate the cellular immune response. This is especially important when working with intracellular pathogens, since immune system cells play a fundamental role in recognising and eliminating infected cells. Of course, this is a hypothesis that now needs to be experimentally validated,” explains Gómez.

Projection: from the laboratory to industry

Currently, the development is in the computational design stage, with promising results, where researchers have already bioinformatically validated the chimeric protein. The next step is to produce it and begin its experimental evaluation.

According to Gómez, the next phases include protein production and purification, in vitro trials, and in vivo studies in fish.

Although still in its early stages, the ultimate goal is to develop a product applicable to salmon farming. However, the scientist explains that they must first evaluate its ability to induce an immune response and, subsequently, conduct challenge studies in fish to determine its protective efficacy.

“That is the goal of all applied research: to transform knowledge into concrete solutions for industry. If the experimental results confirm what was observed in the design, this candidate has significant potential to move towards a practical application,” he concludes.