Scientists at Emory University will use a $10 million grant from the National Institutes of Health (NIH) to develop new strategies for vaccination that can better protect organ transplant recipients and other immune-suppressed patients from infectious disease threats.
The five-year grant from the National Institute of Allergy and Infectious Diseases (NIAID) was awarded to scientists in the Emory Transplant Center, the Emory Vaccine Center and the Yerkes National Primate Research Center. Christian P. Larsen, MD, PhD, director of the Emory Transplant Center, is principal investigator of the NIH grant and Rafi Ahmed, PhD, director of the Emory Vaccine Center, is program director.
Despite vast improvements in the prevention of infectious diseases over the past century, many individuals, including organ transplant recipients, are either unable to receive certain kinds of vaccinations or may not derive the same level of protection from vaccines. Transplant recipients must take drugs to help prevent rejection of their transplanted organs, but these drugs suppress their immune systems and leave them vulnerable to infection. While several vaccines are appropriate and recommended for immune-suppressed patients, it is known that vaccines are less effective in these vulnerable populations. However, emerging knowledge from basic immunology research is giving scientists new insights into the precise effects of vaccines on the immune system and how to improve vaccine effectiveness for these patients.
The challenge of new emerging infectious diseases, the threat of bioterrorism, and the ever-present possibility of pandemic influenza have highlighted the need for new strategies to protect immunocompromised groups from infectious diseases. The new NIH-funded research program should provide new knowledge about the biology of existing and newly developed immunosuppressive drugs for transplant patients and novel ideas about how to improve immune responses in these patients while at the same time protecting their transplanted organs from rejection.
"Thousands of patients have benefited from organ transplantation," says Dr. Larsen, "but a major challenge remains -- the lifelong immunosuppressive drugs these patients must take and the effect the drugs have on overall health and the ability to defend against infections. The growing number of patients who have received transplanted organs and the major threats of global infectious diseases make it imperative that we develop effective ways of protecting these patients from natural or human-caused disease outbreaks."
Broad recommendations that either rule out vaccination for organ transplant recipients or recommend only certain kinds of vaccines do not take into account new developments in transplant drugs or new knowledge about vaccines and immunity, says Dr. Larsen. The recommendations also do not account for individual differences in immune response or changes over time.
"Part of our goal is to develop new strategies that could protect transplant patients from potential bioterrorism agents," says Dr. Ahmed. "Although studies have not been done in transplant patients to test the current smallpox vaccination based on vaccinia virus, individuals with defects in T cell immunity are known to have very serious side effects from vaccination. We believe modified vaccinia Ankara (MVA) vaccine, which is based on a related poxvirus, may be a safer alternative for these patients."
Dr. Larsen, his colleague Thomas Pearson, MD, PhD, director of the kidney transplant program at Emory University, and their research team have worked for the past decade on developing new immune strategies and new kinds of drugs that would be less toxic for transplant patients. Dr. Ahmed, an internationally recognized expert in the mechanisms of immune memory, has been a major collaborator on immune studies with Emory's transplant team.