CAMBRIDGE, MA -- In the United States, children routinely receive an injectable form of the polio vaccine. This vaccine is very effective at preventing illness, but it doesn't block transmission of the polio virus as well as the oral polio vaccine does.
Poliovirus is usually transmitted through contaminated food or water, so the GI tract is where the body is first exposed. Because the oral vaccine induces a mucosal immune response within the GI tract, it is much more effective at preventing infection and spread of the virus. However, there is a small chance that the oral vaccine can become infectious, so many countries have stopped using it.
Researchers at MIT have now come up with a way to modify the injectable vaccine so that it can also promote a mucosal immune response. This vaccine could help to achieve polio eradication while avoiding the risks of the oral polio vaccine.
"People who are vaccinated with the injectable vaccine are not getting sick, but they may be helping the virus circulate. Mucosal immunity could help lower that shedding and ideally eliminate it," says Ana Jaklenec, a principal investigator in MIT's Koch Institute for Integrative Cancer Research.
The researchers' new vaccine consists of the current injectable, inactivated polio vaccine (IPV), delivered with a nanoparticle-based adjuvant that helps steer immune cells to the mucosal lining of the intestine. In a study of rats, the researchers found that this vaccine produced a 20-fold increase in the type of antibodies needed for mucosal immunity, compared to IPV alone.
Jaklenec and Robert Langer, the David H. Koch Institute Professor at MIT, are the senior authors of the study, which appears today in Science Advances. MIT postdoc Behnaz Eshaghi is the lead author of the paper.
Targeting polio
Polio, which can cause paralysis in severe cases, is now rare in most of the world due to extensive vaccination campaigns. The virus is highly contagious and is most commonly spread through consumption of food or water contaminated with the stool of an infected person.
Cases are occasionally seen in the United States and other countries, and the virus is endemic in Pakistan and Afghanistan. While most of these cases are caused by the virus spreading among unvaccinated individuals, some cases may be due to the evolution of the live viruses used in the oral polio vaccine (OPV). These viruses are attenuated, meaning they are alive but weakened. In rare cases, they can mutate and evolve to become infectious again.
It's also possible that wild poliovirus can be spread by people who have received the injected polio vaccine. These people would likely not experience any symptoms, but they could still shed the virus in their stool. Eventually, this could expose someone who isn't vaccinated. Studies have shown that even in countries that with very high polio vaccination rates, the virus can be detected in wastewater.
To boost 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 would also induce mucosal immunity, like the OPV.
In hopes of achieving that, the MIT researchers teamed up with researchers at Harvard Medical School who have shown that using a derivative of vitamin A as a vaccine adjuvant can help stimulate immune cells to go to the GI tract.
That adjuvant, known as Am80, works well, but to generate a strong response, it needs to be injected for several days in a row, which is not feasible for most vaccine campaigns.
To eliminate the need for repeated daily injections, the researchers set out to develop a nanoparticle formulation that would enable the adjuvant to be released slowly over several days. They tested several different types of nanoparticles and found that the one that worked best was a lipid nanoparticle (LNP).
"The purpose of the nanoparticle is making sure that we can engineer a platform with a sustained release of the cargo for a few days," Eshaghi says. "That way we can overcome the bottleneck that for free administration of Am80 you need multiple daily injections."
Mucosal immunity
In tests in rats, the researchers delivered an injection of an inactivated polio vaccine, similar to the one that is now used in the United States, along with a separate injection of Am80 encapsulated in LNPs. After the first dose, boosters were given at four weeks and eight weeks.
After injection, the nanoparticles accumulate in the lymph nodes, where they interact with B and T cells that are also exposed to the polio vaccine. This interaction stimulates the B and T cells to produce two surface proteins that act as homing signals directing them to the GI tract.
The B cells also begin producing a type of antibodies called IgA, which protect body surfaces from infection by coating the mucosal membranes. In addition, the rats also produce IgG antibodies that circulate in the bloodstream, similar to the antibodies that are normally produced in response to the injected polio vaccine.
"IPV is a safe vaccine, but it cannot create mucosal immunity. OPV can create that mucosal response, but it is not as safe," Eshaghi says. "By adding Am80 to lipid nanoparticle as an adjuvant, we are combining the safety of IPV with an adjuvant that can produce the mucosal immunity that normally you can only get with OPV."
The researchers now plan to test the vaccine in additional larger animal models, where they will inject the vaccine and adjuvant mixed together.
Using Am80 or other adjuvants to induce a mucosal response could also help researchers design improved vaccines for other pathogens that infect the GI tract, or for diseases that infect the lungs or reproductive tract.
"You could potentially add it to any vaccine that's injected," Jaklenec says. "This particular work shows that cells can be directed to the gut and increase enteric mucosal immunity. Whether it works for the respiratory or vaginal mucosa is not yet clear."
