The immune system is the body’s best defense against foreign invaders, working hard to help people fight back against pathogens. To bolster the body’s natural defenses, scientists employ vaccines to build up the body's immune response. By imitating an infection, vaccines encourage the body to create tools to recognize and fight these germs, helping prepare for a future full-fledged pathogen attack.
Most current vaccines are injected, but Dr. Renukaradhya Gourapura, a professor at The Ohio State University’s Center for Food Animal Health, thinks there may be more effective methods of getting vaccines into our bodies.
For example, the viruses that cause COVID-19 and influenza mainly infect the body’s upper and lower respiratory tracts. However, due to the way vaccine material is introduced when injected, local, tissue-level immunity doesn’t primarily develop in these areas. Instead, most antibodies (protective proteins) are created in the bloodstream.
While vaccinated people may not end up in the hospital or experience as severe symptoms, this lack of local immunity, especially in the upper respiratory tract, can be a problem, Gourapura says. Because the virus will continue replicating in the nasal passage, people will continue to suffer and shed viral material, leading to further transmission—and evolution—of the virus.
So how can we improve our defenses and come up with a better way to deliver vaccines? Gourapura and a team of College of Food, Agricultural, and Environmental Sciences researchers think the answer lies with the mucosal immune system. Around 80% of the body’s immune cells are found in this system, which is comprised of mucosal tissues that span from head to toe—inside our noses, mouths, and lungs, and even deep inside our guts.
“People are now realizing that induction of local immunity is critical,” Gourapura said. “If we activate the mucosal immune system with good vaccines, we can expect better immunity and decreased transmission.”
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The mucosal system is similar in both animals and humans, so creating vaccines that target it may help reduce the spread and severity of disease in both populations, Gourapura says.
Besides just improving the health of the human population, reducing disease can limit zoonotic spread— when diseases are transmitted back-and-forth between humans and animals. Decreasing disease transmission in agricultural animals can also improve food production by lowering costs for producers, enhancing animal welfare and productivity, and overall leading to better-quality products.
For nearly 15 years at Ohio State, researchers in Gourapura’s lab have been using animal models to explore better vaccination techniques.
“One person cannot find the answer for everything,” he said. “But at least we can make an attempt to find alternate ways to help people’s and animals’ health.”
Anything Nose – Intranasal Vaccines for Influenza and COVID-19
Intranasal vaccines are one promising alternative to injections, but Gourapura knows it’s not easy to induce local mucosal immunity if you don’t have a good vaccine delivery platform. That is, you can’t just put the vaccine material that’s used in injections into the nose and expect it to work.
Nasal passages are crammed full of bristly cilia and gooey mucus, which act as physical barriers blocking foreign agents and particles from entering the body. The nose is extremely good at eliminating pathogens, but unfortunately, that also means it’s skilled at taking out a vaccine’s antigens, or molecules that trigger a specific immune response, before they can produce immunity.
To overcome this problem, Gourapura’s lab has been developing a nanoparticle vaccine delivery system. Only around 300 nanometers big—or about 3,000 times smaller than an ant—these tiny particles act as vessels that can safely take antigen cargo past the body’s defenses and right into the mucosal immune system.
Nanoparticles stuffed with antigens can get closer to mucous membranes and keep antigens there longer, hopefully improving immunity. Gourapura's nanoparticles are made in the lab with a material called chitosan and include only FDA-approved materials.
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Gourapura and the CFAES researchers have tested the effectiveness of intranasal nanoparticle vaccines with the help of a variety of animal models. Pigs are key for influenza research, while hamsters, mice, and ferrets are essential for COVID-19 vaccines. Researchers spray a fine mist into the animals’ noses to immunize them, and then repeat three weeks later with a booster dose. These animals, along with an unvaccinated control group, are then challenged with a virus. Collecting samples like nasal swabs helps researchers understand the amount of virus material present in the animals’ respiratory tracts. They may also study animals’ immune responses and do pathology work.
The team has received a number of patents for intranasal nanoparticle vaccine technologies, with several COVID-19 vaccines currently on the path toward full patent. But as Ohio State’s Center for Food Animal Health only has the infrastructure for testing with animal models, Gourapura’s technologies are in the preclinical stage, with his results serving as a proof of concept that this type of vaccine formulation works. Gourapura hopes that going forward, other companies can take Ohio State’s patents and perform human trials, further developing these vaccines.
Getting Mouthy – Oral Vaccines for Salmonella
A common type of food poisoning is salmonellosis, an infection caused by several species of salmonella bacteria. These bacteria are found in chickens’ intestines and reproductive tracts, and when chicken and eggs are processed, they may become contaminated. If these products are not properly cooked before they’re eaten, people can get sick; the CDC estimates that each year in the U.S., about 1.35 million infections, 26,500 hospitalizations, and 420 deaths are caused by salmonella bacteria.
Dr. Gourapura’s team is working to create an oral vaccine for poultry that will help reduce this problem. Just like with COVID-19 and flu, researchers think nanoparticles could be an effective way to deliver salmonella antigens to chickens’ mucosal systems and spur immunity. But, instead of up the nose, the vaccine could be delivered via the mouth.
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CFAES researchers developed a special type of nanoparticle that can carry a salmonella vaccine past chickens’ bodily front lines: one with flagella, super-speedy whip-like structures that improve mobility. These flagella-powered particles efficiently deliver the vaccine to the small intestine, where it enters chickens’ immune cells and induces local immunity, reducing the colonization of salmonella.
Researchers tested the vaccine by giving chickens drops in their mouths and mixing it into their feed or drinking water. Their results showed that the vaccine did induce local immunity in the birds’ small intestines and reduced salmonella load.
Going forward, the team is seeking grants that will enable them to further test feed and water delivery for these types of oral vaccines.
- Get to know CFAES’ Dr. Gourapura
- Learn more about Ohio State’s Center for Food Animal Health
- Read more about COVID-19 nasal vaccine research
- Explore research about COVID-19 and mucosal immunity
- Read more papers about nanoparticle vaccines
- Learn more about chitosan nanoparticles