Immunogenicity of Group B streptococcus (GBS) in fish following vaccine delivery via pH-responsive vaccine carriers within the feed

Summary

Group B Streptococcus (GBS) is widely known as cause of disease in babies. It also causes disease in fish with significant impact on fish survival and farmers’ livelihoods in low or middle-income countries, e.g. in Vietnam, where fish farming makes crucial contributions to food security and the economy.  Worryingly, GBS from fish can cause sepsis in otherwise healthy people following foodborne transmission. This emerging disease is of such concern that the FAO Regional Office for Asia Pacific recently commissioned a Risk Profile on foodborne GBS. To combat the threat of GBS, antimicrobials are commonly used in fish farming, but this creates the risk of selection for antimicrobial resistance.

Vaccines are urgently needed as alternative method of GBS control. To be economically viable in tilapia aquaculture, oral delivery of vaccines is needed. We have developed a novel approach to oral vaccination using pH-dependent targeted delivery to the fish gut.

We now seek to establish the host immune response to GBS bacterin vaccines delivered with this methodology. To this end, we will conduct vaccination and challenge studies, and evaluate the immune response and protection induced by our prototype vaccine.  The project, led by a UK and Vietnamese mid-career scientist, will bring together a unique combination of expertise in immunology, aquaculture, pharmaceutical and veterinary sciences to advance a novel approach to fish vaccination with specific application to GBS.  The project will demonstrate the feasibility of this new platform technology, which could be adapted across a range of host and pathogen species.

Project Outcomes

Tilapia is the third most farmed fish species in the world with the global market value of US $7.9 billion in 2020. In many low or middle-income countries, including Vietnam, tilapia aquaculture forms a crucial part of the economy, employing and feeding millions of people. However, regular disease outbreaks on farms cause waste, loss of income and even foodborne illness in humans (e.g. due to Group B Streptococcus, or GBS). Large amounts of antibiotics are used in aquaculture to control diseases. In order to reduce the risk of antimicrobial resistance in aquaculture, the industry actively seeks sustainable solutions such as vaccines. Most of the vaccines available for disease control in tilapia are injectable formulations. They are only suitable for fish that are large enough to be handled and anaesthetized. The use of oral vaccines in fish, therefore, has crucial advantages over injection. However, the development of oral vaccines for fish is considered hampered, among other things, by potential antigen degradation in the stomach before they reach the site of absorption. 

 In this project, we have developed a novel pH-responsive polymer encapsulated oral vaccine to prevent GBS disease in tilapia. The new technology allows administration of vaccines as a part of the feed, with release of vaccine cargo once the feed is ingested by fish. Under the experimental conditions, the novel oral vaccination was able to protect over 50 % of the vaccinated population from mortality. The fish's immune competency mechanisms were assessed by measuring specific serum antibody titres and gene expression. The antibody titre was measured using an enzyme-linked immunosorbent assay (ELISA) established during this project and showed significantly increased IgM levels in vaccinated fish. The fish-specific mucosa-associated immunoglobulin, IgT transcripts and T-related gene transcripts were significantly upregulated in the vaccinated fish compared to unvaccinated fish. With the high level of survival of fish in the group vaccinated using the gavage method, we assume that an increased level of antigen reaching the intestine may improve vaccine efficacy further. Further modification of the pH-responsive particles may help to achieve this, and to develop cost-effective approaches to fish vaccination.