Other Research Areas

Besides leading programs for cholera, enteric fever, dengue and MERS, IVI conducts research on hepatitis E and provides Asia-based support to partners in vaccine development for other diarrheal diseases (rotavirus, shigellosis, Enterotoxigenic E. coli, norovirus, tuberculosis, and pneumococcal disease.

These are diseases that exert a high disease burden in global health and are of particular concern to countries in Asia and Africa.

DRPK Program

Japanese encephalitis (JE) and Haemophilus influenzae type b (Hib) – both infections of the central nervous system that can result in severe neurological disease – are thought to have substantial incidence rates among children in the Democratic People’s Republic of Korea (DPRK; North Korea).

In 2007, IVI launched a program for the prevention and control of Hib and JE in North Korean children in partnership with the Academy of Medical Sciences (AMS), North Korea’s main center of medical research, with funding from South Korea’s Ministry of Unification.Since then, the DPRK Program has focused on strengthening the country’s capacity to diagnose and conduct surveillance for Hib and JE, as well as for diarrheal diseases.

Activities have included:

  • Training of North Korean scientists in lab-based methods for Hib and JE diagnosis using international standard procedures;
  • Assistance with the establishment of a reference diagnostic laboratory at AMS in order to properly diagnose cases of meningitis or encephalitis presented at healthcare facilities throughout the country; and
  • Assistance in the coordination of pilot vaccination campaigns against JE and Hib in Sariwon and Nampo cities in 2008, which resulted in the launch of a phased country-wide vaccination of children with the SA-14-14-2 JE vaccine in 2009.

PROVIDE

PROVIDE is a research study funded by the Bill & Melinda Gates Foundation that seeks to uncover the role of tropical enteropathy on the immune response to oral vaccines. Tropical enteropathy is a disturbance in the intestinal lining that makes it difficult for the body to absorb nutrition and is often observed in children from low-income countries. It has also been observed that children from low-income countries have a decreased immune response to oral vaccines compared with children from developed countries.

With India’s National Institute of Cholera and Enteric Diseases (NICED), University of Virginia, and University of Vermont, IVI has embarked on an observational study to see if there is a relationship between children with tropical enteropathy and those who do not respond well to oral polio and rotavirus vaccines. The study will also identify if maternal breast milk has a role in the child’s immune response to vaccines; how a child’s nutritional status is related to this problem; and if some children may be more likely to develop tropical enteropathy compared with others.

The study enrolled 372 infants at the hospital study site in Kolkata, India. All infants, as part of their routine immunization, received the EPI vaccines, as well as the oral rotavirus vaccine (Rotarix). For the polio vaccine, infants were randomized into two groups with one group receiving the injectable polio vaccine (IPV) and the other group receiving the oral polio vaccine (OPV). All of the lab tests were conducted at the IVI /NICED Immune-monitoring laboratory.

Preliminary analyses suggest there is a poor immune response to oral rotavirus vaccines with immunogenicity less than 40 percent. Furthermore, there appears to be a negative correlation between maternal breast milk antibody titers and the infant’s immune response to vaccination, suggesting that breast milk antibodies may interfere with the infant’s gut immune response. Other factors such as infant’s age at enrollment, maternal BMI, maternal zinc supplementation and poor breastfeeding were associated with the child’s antibody response to the rotavirus vaccine.

Moving forward, the polio immunogenicity data will be completed, and preliminary and secondary data analyses will be done. Additional biomarkers will be tested to identify the interference of tropical enteropathy, as well as the role of gut homing cells as a correlate of protection in rotavirus infection.

Based on the PROVIDE data, IVI has initiated work on developing a rotavirus conjugate vaccine. The process development and clinical immunology teams are working together to develop an vaccine for developing countries.