Rotavirus Vaccine Close to Market
Faculty Profile: David Bernstein and Richard Ward, Infectious Diseases
A vaccine developed by researchers in the Cincinnati Children's Division of Infectious Diseases, now in Phase III international testing, may soon hold the key to preventing death due to rotavirus in children in developing countries.
A severe diarrheal illness of childhood, rotavirus infection accounts for more than 500,000 physician visits and approximately 50,000 hospitalizations each year among children under age 5 in the United States. In developing countries, however, rotavirus infection continues to be a childhood killer, taking more than half a million young lives each year.
David Bernstein, MD, MA, and Richard Ward, PhD, first isolated a human rotavirus strain in 1988 that they developed into a live, orally-deliverable vaccine candidate under a licensure agreement with Avant Immunotherapeutics, Inc. After a highly successful but small Phase II efficacy trial led by Drs. Bernstein and Ward, Avant sublicensed this vaccine candidate to GlaxoSmithKline in 1997. The trial results, published in The Lancet in 1999, showed the vaccine to be 89 percent effective in preventing rotavirus disease in infants.
The need for a safe, effective rotavirus vaccine became even more urgent four years ago when the only licensed rotavirus vaccine was removed from the market because of an association with bowel blockage in children who had received the vaccine. Today, there are no licensed vaccines against rotavirus.
Currently, two vaccines are being evaluated in Phase III clinical trials, one by GlaxoSmithKline and the other by Merck. Because of the previous vaccine's complications, both companies are conducting very large trials (60,000 subjects or more) to assure safety. Merck is testing its vaccine predominantly in the United States, while GlaxoSmithKline is testing Drs. Bernstein and Ward's vaccine in less-developed, as well as developing, nations.
The GlaxoSmithKline trial represents the first time that a Phase III, prelicensed vaccine has been tested first in less developed countries -- in this case, bringing early relief to the children who need it most. Drs. Bernstein and Ward continue to serve as consultants to GlaxoSmithKline, and perform the majority of the laboratory work at Cincinnati Children's.
Results to date have not revealed an association with bowel blockage. Initial concerns about the ability of a single human rotavirus strain to provide protection against unmatched strains of rotavirus also appear to be unfounded, as the vaccine has provided protection against at least one other serotype in recent trials. The researchers hope to see the vaccine licensed within the next two years.
Dr. Ward and Anthony Choi, PhD, also at Cincinnati Children's, have secured a patent for a second vaccine -- a protein rather than a live rotavirus vaccine -- that could become a second-generation option if bowel blockage or other complications arise from the live rotavirus vaccine.
