By KRISTA CONGER
About 2,000 children die each day in developing countries from severe diarrhea caused by rotavirus infection. A collaboration between researchers at the medical center and their colleagues at the Centers for Disease Control and Prevention and in India aims to change that appalling statistic.
The group recently received more than $6 million from American and Indian funding agencies to develop and manufacture a rotavirus vaccine in India.
The effort is a unique attempt to shorten the lag, which can approach decades, between the development of a vaccine in this country and its availability in the neediest parts of the world. It may provide a model to enable other developing countries to improve public health.
Harry Greenberg (third from left) and colleagues Ms. Krishna Ella, Durga Rao and Roger Glass, among others, met last month in Hyderabad to kick off a five-year effort to develop and manufacture in India a vaccine for rotavirus, a deadly disease that kills hundreds of thousands of children annually. PHOTO: COURTESY OF HARRY GREENBERG
"This is an amazing experiment," said Harry Greenberg, MD, the Joseph D. Grant Professor in the School of Medicine and senior associate dean for research. "If this works, it will mean that the Third World and the First World will come online at the same time."
The five-year effort will capitalize on two unique, naturally occurring strains of rotavirus that Greenberg and his colleagues isolated from Indian newborns several years ago. Unlike other strains, these variants infect babies without causing symptoms because the troublesome portions of the human virus have been exchanged with a rotavirus that usually infects only cows. The switch robs the virus of its ability to wreak intestinal havoc in humans.
"The fact that they don’t cause diseases in babies may make them perfect for protection," said Yvonne Maldonado, MD, the Stanford lead investigator.
All children worldwide are infected by rotavirus within the first few years of life, and typically the first infection is the most deadly. Symptoms tend to lessen in severity with each subsequent infection.
"We’d like to use these strains to develop a vaccine for young babies that will give them an exposure without the symptoms," said Maldonado, associate professor of pediatrics. "Then when they are exposed to wild type virus, they’ll act like it’s their second or third infection. We’re striving not to prevent infection, but to prevent disease."
Maldonado, Greenberg, investigators at the CDC and the Indian researchers are used to working together. For more than 10 years, they’ve collaborated as part of the Indo-U.S. Vaccine Active Program to isolate the new candidate rotavirus strains and produce test lots of the vaccine. But the release in 1998 of a new rotavirus vaccine in America seemed to reduce the urgency of their mission — until it was recalled in 1999 after being linked to an increase in a sometimes deadly bowel condition.
The new infusion of funds, partly in the form of a research grant to Stanford and the All India Institute of Medical Sciences from the National Institute of Allergy and Infectious Diseases, will allow the researchers to conduct formal clinical trials of the vaccine in India. The grant is supported in part by the Children’s Vaccine Program at the Program for Appropriate Technology in Health, or PATH, which receives funding from the Gates Foundation. The money will also enable Bharat Biotech, an Indian biotechnology company, to scale up their facilities to produce large amounts of high-quality vaccine.
Greenberg and Maldonado, who has extensive experience in designing clinical trials in developing countries, will work with their Indian colleagues to design tests of the safety and efficacy of the vaccine. They, along with Roger Glass, MD, and other scientists at the CDC, will facilitate the development of good scientific leadership and practices through distance-learning courses and onsite instruction at Stanford, the CDC and in India.
"This is an ideal collaboration because we have these great investigators in India who are going to do all the clinical work," said Maldonado. "It’s up to us to make sure their work is based on good documentation and statistics." They will ensure that vaccine development and manufacture adheres to the international standard of Good Clinical Practice.
Although all of the researchers are excited about the novel aspects of their collaboration, ultimately the health of the affected children is their main concern. "This isn’t theoretical," said Maldonado. "This is a major cause of death in children worldwide. If the vaccine works well, it is going to make a big difference in children’s health. It’s bench-to-bedside in action."
Stanford Report, November 6, 2002