Enteric disease: Achilles heel of oral vaccines
Oral vaccines – administered by mouth – have characteristics advantageous for use in low-income countries as a means of reducing the burden of infectious disease. They eliminate the need for syringes that pose a risk of contamination and can be administered by health professionals less experienced than syringe-based vaccines, increasing accessibility.
However, oral vaccines are less immunogenic when given in low-income countries than in high-income countries. Several factors can contribute to this reduced efficiency. One example is bowel disease, such as environmental enteric dysfunction (EED), which is prevalent in countries with poor sanitation. However, the precise biological mechanisms by which these diseases reduce the efficacy of the oral vaccine are poorly understood. A new study by UPMC Children’s Hospital of Pittsburgh and scientists at the University of Pittsburgh School of Medicine used a mouse model of EED to further study this phenomenon and seek possible solutions.
Dr Timothy Hand, assistant professor in the departments of pediatrics and immunology at the University of Pittsburgh, is the lead author of the new study. Technological networks Hand interviewed to learn more about the study results, the role of the microbiome in vaccine effectiveness, and how we can seek to reduce oral vaccine failure.
Molly Campbell (MC): Can you explain what an oral vaccine is and how it activates the immune system? How does this differ from other administrative routes, such as a vaccine injected intramuscularly, for example?
Hand of Timothy (TH): Oral vaccines differ from more traditional vaccines in two main ways. First, they are administered orally and do not require a syringe. More importantly, oral vaccines provide superior protection at “mucosal barrier” sites (eg, intestine, lungs, nose, etc.). Since most infections pass through these sites, protecting these barriers can be very effective, preventing bacteria / viruses from gaining a foothold in the body.
MC: Why are oral vaccines beneficial for areas of the world with poor sanitation?
E: Sanitation prevents gastrointestinal infections. As mentioned above, oral vaccines are better at preventing intestinal infections, so they are beneficial in places where these infections are common.
MC: In your new study, you explored the impact of the intestinal disorder, environmental enteric dysfunction (EED), on oral vaccine success using a mouse model of the disease. Can you discuss the rationale for your study?
E: Places around the world where EED is common also show very low efficacy of oral vaccines. It was long believed that some of the symptoms of EED (less bowel area and infiltration of immune cells into the gut) could contribute to this failure, but this has never been clearly demonstrated. The study of EED in humans is difficult; Obtaining small intestine biopsies is difficult and even more difficult for people living in low to middle income countries (LMICs) with DED. A mouse model is very useful in allowing us to advance biology in this area. Our mouse model mimics human EED in multiple ways, mice exhibit growth retardation, microbiome changes, intestinal damage and leakage and do not respond effectively to oral vaccination.
MC: You discovered that the microbiome was involved in the failure of the oral vaccine in EED. Can you expand on this and how we might seek to target the microbiome to avoid such a failure?
E: We will hypothesize that in order to “fix” the EED, we need to reset the microbiome. We would say that the judicious use of antibiotics followed by the restoration of a healthy diet would allow just such a reset. These patients could then be vaccinated to prevent the cycle of infection, malnutrition, inflammation and dysbiosis in the microbiome that underlies this disease.
MC: The study was done on mice. How might the results translate to humans?
E: We believe that our model reflects the human condition quite well and, as we have demonstrated, offers the possibility of mechanically testing what is going on with regard to the immune response and the microbiome that lead to the disease. We would like to see if any of the phenomena we have observed that cause EED in the mouse model are shared by humans with EED. Such findings would allow us to move forward with targeted therapies to restore gut health and mucosal immunity in patients with EED.
MC: What are your next research steps in this space?
E: We hope to collaborate with researchers studying oral vaccines in humans to see if our results are relevant to what happens in humans with EED. We think our model still has a lot to teach us about how the gut, immune system, and microbiome work together to respond to malnutrition.
MC: What else can be done to combat oral vaccine failure?
E: PRFIs need better toilets. We need the whole world to be able to safely manage their waste.
Timothy Hand was speaking to Molly Campbell, science writer for Technology Networks.