Rotavirus vaccine will protect children against a major killer worldwide

The Food and Drug Administration (FDA) has announced the licensing of a new vaccine against a disease responsible for tens of thousands of hospitalizations in the United States and hundreds of thousands of deaths around the world each year.

The vaccine, developed by Merck & Co., Inc., will be sold as ROTATEQ. and will protect infants against rotavirus infection. Rotavirus is a highly contagious virus that is the most common cause of severe dehydrating diarrhea in infants and young children.

The early research that underpins the new vaccine was conducted by three scientists at The Wistar Institute and The Children's Hospital of Philadelphia (CHOP) between 1980 and 1991, at which time Merck took on the task of developing the vaccine for the clinic. The scientists are H. Fred Clark, D.V.M., Ph.D., Paul A. Offit, M.D., and Stanley A. Plotkin, M.D. Clark and Offit are currently on faculty at CHOP, where Clark is a research professor of pediatrics and Offit is chief of infectious diseases and the Maurice R. Hilleman Endowed Chair in Vaccinology; both are adjunct professors at Wistar. Plotkin, an emeritus professor at Wistar, was the developer of a number of vaccines, including the rubella vaccine responsible for eradicating that disease in the United States, according to the Centers for Disease Control.

"This new vaccine against an important disease of childhood is the result of two leading academic research institutions and a major pharmaceutical company working together toward a common goal for roughly 25 years," says Russel E. Kaufman, M.D., president and CEO of The Wistar Institute. "It has been a long road, and we are very proud of the role our scientists played in the success of this important medical advance."

Plotkin and Clark began work on rotavirus in 1980. In 1981, Clark, a veterinarian, isolated from a calf the strain of rotavirus - dubbed the Wistar Calf-3, or WC3, strain - that would provide the foundation for the new vaccine. That same year, Offit joined Plotkin and Clark in the effort to develop a vaccine against rotavirus. As a senior resident at a hospital in Pittsburgh in 1979, Offit had witnessed the death of a nine-month-old boy from rotavirus infection, and he welcomed the opportunity to work on a vaccine to combat the disease.

Early studies with the WC3 strain indicated that while it was safe for use as a vaccine, it did not provide sufficiently effective protection against rotavirus infection. During the 1980s, the team turned to the idea of reassortants, taking advantage of the fact that viruses have the ability to borrow genetic material from each other to "reassort" themselves into new strains.

By co-infecting cells in culture with the WC3 strain of rotavirus and five different human rotavirus strains known as G1, G2, G3, G4, and P1, the scientists were able to create a reassortant bovine-human rotavirus virus that promised improved protection against rotavirus disease. Specifically, the reassortant virus incorporated the human versions of two proteins called VP4 and VP7, found on the surface of the virus and known to play roles in the immune response to the virus. The three scientists were subsequently awarded a series of U.S. and international patents for the rotavirus reassortant vaccine.

Merck assumed financial support of the project in 1991, and after licensing the technology from Wistar and CHOP in 1992, the company moved toward clinical development and testing of the vaccine. From 1993 to 2005, Merck conducted studies to determine the safety, efficacy, dose, buffer combinations, and serotype composition of the vaccine. Between 2001 and 2004, the company conducted one of the largest clinical trials of a vaccine ever performed by a pharmaceutical company, involving 70,301 infants in 11 countries. On December 14, 2005, the FDA's Vaccines and Related Biological Products Advisory Committee voted unanimously that the clinical data from that trial supported the safety and efficacy of ROTATEQ, setting the stage for today's announcement by the agency.

The new vaccine promises to become a major new tool to promote public health. In the United States each year, rotavirus is thought to account for approximately 500,000 physician visits, 250,000 emergency room visits, 50,000 hospitalizations, and 20 to 60 deaths among children under 5 years of age. In developing countries, where medical care may be inadequate or unavailable, rotavirus infections can be even more deadly. Estimates range between 440,000 to 600,000 deaths worldwide every year.