In the United States, children routinely receive an injectable form of polio vaccine. Although this vaccine is highly effective in preventing disease, it does not prevent poliovirus transmission as well as the oral polio vaccine.
Poliovirus is usually transmitted through contaminated food or water, so the body’s first exposure is through the gastrointestinal tract. Oral vaccines induce a mucosal immune response within the gastrointestinal tract and are therefore much more effective at preventing viral infection and spread. However, because oral vaccines are less likely to cause infection, many countries have suspended their use.
Now, researchers at MIT have devised a way to modify an injectable vaccine so that it also stimulates a mucosal immune response. This vaccine could help achieve polio eradication while avoiding the risks of oral polio vaccines.
Although people who have received the injectable vaccine have not become ill, they may be contributing to the circulation of the virus. Mucosal immunity may help reduce its shedding and ideally eliminate it. ”
Ana Jaklenec, Principal Investigator, Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology
The researchers’ new vaccine consists of the current injectable inactivated polio vaccine (IPV), delivered with a nanoparticle-based adjuvant that helps guide immune cells to the mucosal lining of the intestine. In a rat study, researchers found that the vaccine increased the types of antibodies required for mucosal immunity by 20-fold compared to IPV alone.
Jakurenek and Robert Langer, a professor at the David H. Koch Institute at the Massachusetts Institute of Technology, are lead authors of the study, which was published today. scientific progress. MIT postdoctoral fellow Behnaz Eshaghi is the paper’s lead author.
target polio
Polio, which can cause paralysis in severe cases, is now rare in most countries around the world thanks to mass vaccination campaigns. This virus is highly contagious and is most commonly spread by ingesting food or water contaminated with the stool of an infected person.
The virus is endemic in Pakistan and Afghanistan, with occasional cases seen in the United States and other countries. Most of these cases are caused by viruses that spread among unvaccinated people, but some cases may be due to the evolution of the live virus used in the oral polio vaccine (OPV). These viruses are attenuated. That is, the virus is alive, but weakened. In rare cases, they mutate and evolve to become infectious again.
Wild poliovirus can also be spread by people who have received the injected polio vaccine. Although these people probably won’t experience any symptoms, they can still shed the virus in their stool. Ultimately, unvaccinated people may become infected. Studies have shown that the virus can be detected in wastewater even in countries with very high polio vaccination coverage.
To increase the chances of completely eradicating polio, it would be ideal to use a vaccine that cannot evolve to cause infection, like the current injectable IPV, and that also induces mucosal immunity, like OPV.
In hopes of achieving that, MIT researchers collaborated with Harvard Medical School researchers who have shown that using vitamin A derivatives as vaccine adjuvants helps stimulate immune cells to go to the gastrointestinal tract.
The adjuvant, known as Am80, is effective, but it needs to be injected over several days in a row to produce a strong response, which is not possible in most vaccine campaigns.
To eliminate the need for repeated daily injections, researchers set out to develop nanoparticle formulations that could release adjuvants slowly over several days. They tested several different types of nanoparticles and found that lipid nanoparticles (LNPs) were the most effective.
“The purpose of nanoparticles is to be able to reliably design platforms that release cargo sustainably over several days,” Eshaghi says. “This would overcome the bottleneck of requiring multiple daily injections to administer Am80 for free.”
mucosal immunity
In experiments on rats, the researchers administered an injection of an inactivated polio vaccine, similar to the one currently used in the United States, along with another injection of Am80 encapsulated in LNPs. After the first dose, booster immunizations were administered at 4 and 8 weeks.
After injection, the nanoparticles accumulate in the lymph nodes, where they interact with B and T cells that were also exposed to the polio vaccine. This interaction stimulates B and T cells to produce two surface proteins that act as homing signals toward the gastrointestinal tract.
B cells also begin producing a type of antibody called IgA, which protects body surfaces from infection by coating the mucous membranes. In addition, rats also produce IgG antibodies that circulate in their bloodstream, similar to the antibodies normally produced in response to an injected polio vaccine.
“IPV is a safe vaccine, but it cannot create mucosal immunity. OPV can create a mucosal response, but it is not as safe,” Eshaghi says. “By adding Am80 as an adjuvant to lipid nanoparticles, we are combining the safety of IPV with an adjuvant that can generate mucosal immunity that is normally only obtained with OPV.”
Researchers now plan to test the vaccine in a larger animal model, in which patients are injected with a mixture of the vaccine and an adjuvant.
Inducing mucosal responses using Am80 or other adjuvants could also help researchers design improved vaccines against other pathogens that infect the gastrointestinal tract, or diseases that infect the lungs or reproductive tract.
“It could potentially be added to any vaccine that is injected,” Jakulenek said. “This particular study shows that the cells can be directed to the intestine and increase intestinal mucosal immunity. Whether it acts on the respiratory or vaginal mucosa is not yet clear.”
This research was funded by the Gates Foundation.
sauce:
Massachusetts Institute of Technology
Reference magazines:
Eshagi, B. Others. (2026). Am80 lipid nanoparticles function as an intestinal mucosal adjuvant after parenteral immunization with inactivated polio vaccine. scientific progress. DOI: 10.1126/sciadv.aea5433. https://www.science.org/doi/10.1126/sciadv.aea5433
