Vaccines and Immunotherapies
Center Leader: Terri Finkel, MD, PhD; Co-leaders: Steven Douglas, MD; with Paul Offit, MD
Researchers harnessed the protective powers of the immune system for medicinal purposes with the development of modern vaccines more than a half-century ago. Nevertheless, infectious diseases remain the leading cause of death for children around the world, and researchers are exploring new ways to use vaccine technology to eliminate this threat.
The immune system sometimes continues its attack long after it eliminates the invading disease. Immune system dysfunction is involved in autoimmune disorders as varied as asthma, inflammatory bowel disease and rheumatoid arthritis. While autoimmune disorders often develop during childhood, they are debilitating chronic illnesses that last a lifetime. As discoveries in the laboratory shed light on the healing potential of the immune system, vaccines will be developed to correct autoimmune disorders by halting the immune system’s mistaken attack on the body itself.
New vaccines also are being developed to help the immune system recognize and eliminate cancer. Unlike infectious diseases against which the immune system is prepared to defend, cancer evades detection. Unfortunately, traditional treatments designed to kill cancer also destroy healthy cells, leaving the immune system weak and the body defenseless.
Because numerous diseases involve a component of immune system dysfunction, the Vaccines and Immunotherapies Affinity Group – including researchers from such different fields as cancer research, gene therapy, immunology, infectious disease, rheumatology and vaccine development – is applying shared knowledge toward a better understanding of the immune system and its powers to protect and heal.
Infectious disease research at the Hospital is focused on developing a safe and effective vaccine against rotavirus, the most common cause of diarrhea and dehydration in children. One product of this research is a newly developed oral vaccine delivery system that could one day eliminate the need for needles, making vaccines easier and more cost effective to administer, especially in the developing world.
In 2006, the U.S. Food and Drug Administration approved RotaTeq®, the rotavirus vaccine developed at Children’s Hospital and The Wistar Institute and further developed by Merck & Co. The federal government’s Advisory Committee on Immunization Practices now recommends that the vaccine become part of the routine infant immunization schedule.
Another infectious disease with global impact is HIV. Standard vaccines for HIV have so far proven ineffective because the virus has evolved to include sophisticated methods for evading detection by the immune system. Hospital researchers are working to understand how HIV invades cells and evades detection by the immune system and designing compounds and delivery systems that target the cells that HIV invades.
For example, investigators are supported by NIH-funded program project, translational research, and biotechnology grants to develop new therapeutics and vaccines against HIV. Clinical trials of pediatric AIDS treatments in development are conducted through the Philadelphia International Maternal Pediatric Adolescent AIDS Clinical Trials (IMPAACT) Unit, located collaboratively at the Children’s Hospital and the Hospital of the University of Pennsylvania.
Refining treatments for neuroblastoma, the most common and deadly form of solid-tumor cancer in children, is another focus of this research affinity group. Until recently, the standard of care for children with neuroblastoma – a combination of surgery, chemotherapy and stem cell transplantation – achieved survival rates of only 35 percent. Investigators are focused on new ways to boost the natural immune response of patients during recovery from stem cell transplantation, a time when patients are extremely vulnerable to life-threatening infections or relapse of cancer.
In addition, Children’s Hospital researchers are developing a better understanding of autoimmune disorders, the role of genetics and the ways in which infectious diseases alter immune system functioning. Investigators are working to develop immune therapies for juvenile rheumatoid arthritis, dermatomyositis and lupus using an immune therapy designed for treating lymphoma. Researchers are also investigating the high vaccine failure in children with certain genetic disorders causing immunodeficiency and autoimmunity, and are developing strategies for enhancing vaccine delivery.