Summer 2012

Living Science

Admin Fadl's next step is to make sure his vaccine is capable of blocking or reducing the colonization of salmonella in the intestinal tract of chickens. Photo by Sevie Kenyon BS'80 MS'06

As a veterinarian in Sudan, his home country, Amin Fadl worked with large poultry producers in the Khartoum area to optimize the health and growth of their flocks. In 1993, he moved to the United States to attend the University of Connecticut, where he earned his master’s and doctoral degrees in microbiology. Now an assistant professor of animal sciences at CALS, Fadl brings his various experiences to bear in the classroom, where he teaches “Animal Science 320: Animal Health and Disease Management,” and in the lab, where he is developing a poultry vaccine against salmonella.

Let’s start with salmonella. What is it and how does it get in our food supply?

Salmonella is one of the major foodborne pathogens. It’s a zoonotic pathogen, which means it can be passed between humans and animals. Humans mostly get infected by eating contaminated meat from infected animals. Unfortunately, a significant number of chickens in our nation’s poultry operations are carriers of this pathogen. They have it in their intestines but don’t show any symptoms or signs of sickness. So during meat processing, salmonella from the intestines can sometimes contaminate the carcass, the meat. As for eggs, salmonella either can be on the outside, on the eggshell, or inside, in the yolk. A significant proportion of eggs are contaminated, so that’s why people always recommend that eggs be cooked properly before eating.

How big of a problem is this?

It’s big. According to the Centers for Disease Control and Prevention, there are about two million cases of salmonella infection in humans every year, but many people just have minor abdominal cramps so they don’t go to the hospital. About 43,000 people actually go to the hospital and provide samples that confirm salmonella infection.

And it can be a big problem for poultry producers, too. Consider last summer’s salmonella outbreak that was linked back to an Iowa egg-producing farm. Many millions of eggs had to be recalled, so that was a huge economic loss. And not only that, but production on this farm was basically stopped for a significant period of time—months—until regulators made sure that they had cleaned everything, sanitized everything and figured out the source of the contamination.

Overall, salmonella is believed to have a total economic cost of more than $1 billion dollars per year.

How would an animal vaccine help?

The whole issue here is how we are going to reduce salmonella outbreaks in humans. Our approach is to stop the infection at the source. Before chickens are harvested, we want to make sure that they are free of salmonella. One way to do this is by administering a vaccine that inhibits the colonization of salmonella in the intestinal tract. This breaks the chain of infection at the source.

How does your vaccine work?

Our vaccine is a weakened form of the pathogen. It’s called a live attenuated vaccine. To make it, we deleted a gene from the salmonella genome known as gidA, which controls the production of a suite of disease factors and co-factors. You can immunize mice with our mutant strain, and then challenge the animals later with a lethal dose of regular salmonella and nothing happens. They stay healthy.

Now we need to test it in chickens to make sure that this vaccine is indeed capable of blocking or reducing the colonization of salmonella in the intestinal tract of these animals. If it does, we can look to take it to the next level.

When will your vaccine become commercially available?

It’s a long process. There are several steps that any potential vaccine must go through before it can be licensed to be used in animals or humans. There’s the lab work, clinical trials, safety testing, quality testing. And after that comes the process of commercial manufacturing. If everything goes well, it’ll take five to 10 years.

Are there salmonella vaccines already on the market?

I only know of one vaccine that’s on the market right now, although some others are currently being developed. So far, vaccinating chickens in the United States against salmonella isn’t routine, as it is in Europe. In Europe there is a different form of salmonella that is really nasty. It produces a very high mortality rate in chickens. With the help of the vaccination they were able to reduce the number of outbreaks and mortality in the European poultry industry. They have been vaccinating for the past decade or more.

Fortunately, we don’t see that form of salmonella much in the United States, so there isn’t a huge market here for a vaccine right now. But we don’t know what will happen later on. The USDA and the FDA could decide that animals must be vaccinated.

How is your vaccine different or better than the other vaccines out there?

There are three important things for a salmonella vaccine: It’s protective, it reduces salmonella colonization in the gut and it produces mucosal antibodies. Our vaccine could be better on one or more of these fronts, but you never know. The data is going to tell us that.

There are actually two types of vaccines—live attenuated vaccines like ours and killed vaccines—each with pros and cons. Killed vaccines are considered safe because the pathogen is killed, but they only induce a weak form of immunity because they don’t interact with the host immune system in the same way as a live bacterium. Live attenuated vaccines, on the other hand, actually multiply in the host system, interacting with it in the same way that disease-causing pathogens do, so they trigger a stronger immune response and provide better protection. However, people are always concerned that there’s a possibility that the weakened pathogen will revert back to its original pathogenic form.

To address this, we’ve also developed a salmonella mutant that has gidA and another gene knocked out. This double mutant has the same quality, the same protection, the same everything as the single gidA mutant strain. But the good thing about it is that two genes have been deleted, so it’s much safer because it’s much less likely to randomly revert back to the pathogenic form. This is where our vaccine has a real advantage. And we are continuously looking for other factors that we can delete that will make our live vaccine safer, while at the same time maintaining its ability to induce a strong immune response.

What could encourage American poultry farmers to start using salmonella vaccines?

Paying for vaccines is like buying insurance. For example, if you look at the Iowa farm that had the contaminated eggs, maybe the owners will think twice about vaccination because of what they went through. Maybe they will tell you that they would have rather taken the loss in their flock’s weight and productivity for a day or two that comes with vaccination than deal with the whole recall process. And it only costs a few cents per bird to vaccinate.

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