An innovative vaccine to fight Streptococcus suis

Article published in the Journal de médecine vétérinaire of the Université de Montréal on September 9, 2022

Article translated by CRIPA

Read the original article : https://fmv.umontreal.ca/faculte/actualites-et-medias/journal-medecine-veterinaire/news/detail/News/un-vaccin-novateur-pour-combattre-le-streptococcus-suis/

Developing an innovative vaccine to combat a bacteria responsible for causing serious diseases in pigs and humans as part of a research project with Thailand. This is the mission that Mariela Segura, professor in the Department of Pathology and Microbiology at the Faculty of Veterinary Medicine of the University of Montreal, has set herself, in collaboration with her colleagues.

Streptococcus suis is a bacteria that lodges in the respiratory tract and the reproductive system of pigs. It is part of the normal flora of the animal. A pig can carry the bacteria without however developing clinical signs.

When virulent strains are present, predisposing factors such as stress, hygiene conditions and temperature variations can trigger certain diseases in pig populations. When the immune system is weakened, the bacteria can more easily enter the bloodstream, causing diseases such as arthritis, meningitis or septicemia (bacterial multiplication throughout the body). When a pig has septicemia, there is an imbalance in the function of its organs, which can cause its death. In addition to having a negative effect on animal welfare, Streptococcus suis causes economic losses for the pork industry. The disease caused by this bacteria in pigs is present in all countries where pig production is significant.

One interest, several aspects

Ms. Segura became interested in this bacteria for several reasons. "Overall, in my laboratory, I am interested in so-called encapsulated bacteria". These are bacteria covered with a layer of sugar, called polysaccharides. These bacteria hide from the immune system, as if they have camouflage. "This type of bacteria is known to cause serious invasive diseases, both in animals and in humans," she continues.

Streptococcus suis belongs to this family of bacteria. "I was interested because there is very little information available". The other attraction from a scientific point of view is that this bacteria impacts both the animal side and the human side (because zoonotic bacteria). This means that the bacteria can be transmitted from pigs to humans. There is therefore a dual interest: that of animal health and public health.

Ms Segura points out that there is no effective commercial vaccine to combat Streptococcus suis. Moreover producers have very few tools to control infections caused by the bacteria. Antibiotics are given preventively, particularly in Asia. The incidence can be reduced from 20% to less than 5% by administering antibiotics on the farm. But this is a practice that is not recommended, since it increases the development of resistance to antibiotics. It is a global problem. With the gradual introduction, already underway, of new regulations aimed at reducing the use of antibiotics for preventive purposes, the swine medicine requires finding another solution. With this ambitious vaccine project, Ms. Segura hopes to be able to prevent the disease, help animals and reduce the transmission of the porcine bacteria to humans.

Thailand at the heart of the research project

The choice of Thailand to carry out this research project is not fortuitous. The zoonosis caused by Streptococcus suis in Asian countries is much greater and presents a real public health challenge. Hence the interest of collaborating with colleagues from China, Vietnam and Thailand. It turns out that Ms. Segura had already established ties with China and Thailand. "In the past, I had a lot of collaborations with China. There was an outbreak of a very virulent strain transmitted from pigs to humans which caused a high mortality rate. This allowed me to build relationships with Asia and to become aware of this reality".

The impact of transmission of the bacteria is more significant in Asia for two main reasons:

1. In some Asian countries, where there are backyard production systems, there is more contact between animals and humans. Animals or their carcasses are handled with lower or non-comparable biosecurity and hygiene standards than large commercial pig production in the West. On small family farms, producers will sometimes keep sick animals for consumption, simply because their financial situation is precarious. They will handle sick animals rather than euthanize and eliminate them, according to established standards. If this manipulation is carried out without appropriate biosecurity or hygiene rules (for example, without wearing gloves), these producers find themselves at risk of contracting the infection and developing the disease.

2. In Vietnam, Thailand and other Southeast Asian countries, customs may affect the transmission of cases. Indeed, during festivities such as weddings, the population consumes certain typical dishes prepared with raw pig's blood. Since the blood has not been cooked, it can contain the bacteria and can be transmitted to humans. Several cases of infections in humans have been reported in this region of the globe. In addition, since it is food, the entire population is at risk. There is therefore no question here of an occupational disease as in the West. There have been many publicity campaigns to educate the Asian population about the dangers of eating raw pork. However, this is a habit that is difficult to change, since it is deeply rooted in the culture.

The objective is to unite expertise within the framework of the project, in order to carry out laboratory tests and preclinical studies in an experimental farm. In this type of farm, the team of scientists wishes to reproduce the commercial aspect of animal breeding and replicate what is found on the ground in Asia.

One of the advantages of carrying out this work in Thailand is that Asian pigs have a different genetic background from those raised in North America. Certain crossbreedings and certain breeds of pigs are specific to this region. "To test a vaccine that is useful in Asia, it's good to test it in our conditions, but also in their conditions, with their animals," says Ms. Segura.

An innovative approach

Ms. Segura and her team have the ambition to develop a vaccine at low cost while adopting an innovative approach, which is no small task. "It's difficult because when you try to do something innovative, you sometimes end up with a product that is too expensive for the producer. We apply the innovative approach to proof of concept to determine if such an approach could lead to the creation of a vaccine.'' At the basic research, experimental research and proof of concept stage, we worry a little less about the final cost of the product.

After this first step, there is a whole process called the marketing plan. The viability of the product is evaluated there from a commercial point of view, in collaboration with the pharmaceutical industry. The scientific team then tries to improve, optimize and refine the approach to reduce the production costs of the vaccine so that it can be applied in the field.

The approach advocated for the vaccine is already used in human medicine. It is inspired by vaccines produced by a traditional method for humans and which are very effective. This method consists of taking the "armor" of the bacteria to produce a vaccine. However, rather than using the armor produced by the bacteria itself, by carrying out bacterial cultures and then purifying it, the armor of the bacteria is synthesized in a tube by the team of researchers. For this process, they use individual ingredients to reconstruct the armor in a tube. This is called chemical synthesis. By taking ingredients and creating the "recipe" in a tube to ultimately rebuild the armor as if it were a cake, the result is a product that is easier to craft, while lowering costs. From this first creation of artificial armor, the vaccine is developed to ultimately immunize animals. "This process looks very simple in a few words, but it is still very complex to perform and requires significant investment in research", specifies Ms. Segura.

To find out if the vaccine developed can be used in North America, Ms. Segura explains: "If we refer to variants, it's a bit like with COVID. In the case of Streptococcus suis, the variants are called serotypes. The serotypes are well known to scientists and the epidemiology is relatively stable in most countries in the world. Some are more present, more associated with clinical cases. We attacked the armor of one of these variants, a serotype that has been considered clinically important for years and is found in several countries around the world. It is also the most common variant that affects humans."

This could represent an obstacle if the team were suddenly interested in another serotype where the synthesis (i.e. the "recipe" for cooking the armor) was more complex to achieve. Producing a vaccine against another serotype could then take a few more years.

Ms. Segura is collaborating on this project with Todd Lowary from the University of Alberta, and Potjanee Srimanote from Thammasat University in Thailand. "I am part of a large network of researchers who work on everything related to sugars. We call it glycomics," she explains. Ms. Segura began as a member of the pan-Canadian GlycoNet (Canadian Glycomics Network), founded by Mr. Lowary. It was during an annual symposium that she met Mr. Lowary. "We started discussing, sharing common interests. And we started to work together in the synthesis of this sugar armor for the bacteria." Ms. Segura continued to invest in the GlycoNet network. She became a member of the Research Management Committee, then a member of the Board of Directors, and finally appointed to the management committee as assistant director, animal health and agriculture.

Ms Segura knew Potjanee Srimanote, her colleague from Thammasat University in Thailand, a few years ago. The two scientists met at various congresses and symposiums on Streptococcus suis. ''We saw the call for projects for a grant from the International Development Research Center (IDRC)''. It was then that the team was brought together to build the project: Mariela Segura, Todd Lowary, Potjanee Srimanote and Marcelo Gottschalk, full professor in the Department of Pathology and Microbiology at the Faculty of Veterinary Medicine at the University of Montreal. Mr. Gottschalk acts as an expert on Streptococcus suis and a veterinarian, to help develop the entire experimental set up with pigs.

Unplanned challenges

The research project came up against two major pitfalls. It was planned that the team from the University of Montreal would travel to Thailand to work on the experimental design on the farm. There were also to be team meetings between Alberta and Montreal once a year, in addition to two international meetings and a visit from Ms. Srimanote. But the COVID pandemic, followed by the outbreak of African swine fever in Thailand, forced Ms Segura to postpone her travel plans to Asia. "After the pandemic, African swine fever wreaked havoc. All animals on the experimental pig farm had to be euthanized."

The collaboration continued, but in virtual mode. The entire laboratory research portion with animals was maintained during the pandemic. The team was able to continue building the project and deliver results. "For the moment, everything that is experimental in Thailand is on ice, nothing can be done until the African swine fever epidemic is controlled". Ms. Segura hopes to be able to go there in June to continue her studies.

Next summer will also be held an international workshp on Streptococcus suis. "We are preparing for the organization of this event which will take place in Bangkok in June. We do this in collaboration with our colleague, Potjanee Srimanote". Mr. Gottschalk and Ms. Segura are the founding members of this prestigious congress: "This is our 5th edition. The first was organized jointly with China, thanks to a Canada-China grant from the Canadian Institutes of Health Research (CIHR). "It was the first time that all the Streptococcus suis researchers in the world were brought together indoors and it was a great success," she explains.

They also organized the 2nd edition which was held in Argentina. The 3rd event took place in Germany, piloted by German colleagues. Mr. Gottschalk and Ms. Segura took over the organization of the 4th edition which took place in Montreal in 2019. The next workshop in Thailand was made possible thanks to an IDRC grant, in collaboration with Ms. Srimanote and jointly with the organization of the International Symposium on Emerging and Re-emerging Pig Diseases (ISERPD).

A long-term project

The Streptococcus suis research project has just passed a key milestone. “We filed a patent application for the intellectual protection of the creation. We are in the implementation phase. As intellectual property is protected, we will be able to publish,” she explains. The team is now working to improve the technology thanks to a grant from GlycoNet, with the collaboration of a private partner. According to Ms. Segura, a time horizon of 10 years would be realistic to lead to the commercialization of the vaccine.

This vaccine prototype is far from final, but it has already shown its effectiveness in protecting animals against disease in experimental trials. The “recipe” is therefore the correct one. “We succeeded in demonstrating an innovative approach in experimental research, namely transferring an approach used in human medicine for application in veterinary medicine and proving that it was something doable. For me, this is the greatest satisfaction,” she says proudly.

A research project that transposes to the Faculty

A research project like this gives Ms. Segura different opportunities to share her knowledge and expertise with her students. In the undergraduate cycle of the doctorate in veterinary medicine, she introduces her students to the functioning of the immune system and how bacteria interact with it. “The example of bacteria with armor is a good example to give to students. Sometimes you have to be really creative to fight diseases like these, because they are very intelligent pathogenic bacteria.”

She also teaches a course on the introduction to research in veterinary medicine. She draws inspiration from her collaboration with Asia to show students the different career prospects in research, including rewarding international projects. At the graduate level, master's and doctoral students benefit directly from these types of projects by actively participating in collaborative research and through international internships.