NAPA VALLEY, Calif. - Pneumococcal vaccines are undergoing field trials here and abroad, and a vaccine to prevent respiratory syncytial virus (RSV) is undergoing laboratory development, according to George Siber, MD, vice president and chief scientific officer at Wyeth-Lederle Vaccines and Pediatrics in Pearl River, N.Y.
"There are pneumococcal vaccines on the market that are just polysaccharides alone. The problem with those vaccines is though they produce pretty reasonable antibody responses in adults, they don't work in children under 2 years; in these patients you have to conjugate the polysaccharides to the proteins to induce antibodies," Siber said here at the Pediatric Infectious Diseases Society annual meeting.
Seven-valent vaccines are being tested at Kaiser Permanente in Northern California and Finland. The Finnish trial is specifically testing the vaccine's ability to protect against otitis media caused by the pneumococci. In Finland it is customary to "tap the ear of children with otitis media so that one can achieve a microbiological diagnosis," said Siber. That procedure is not normally done elsewhere, he noted.
The studies done in this country don't have a specific duration. "The analyses will be done when certain numbers of cases have been observed," Siber said.
Meanwhile in South Africa, a trial of a nine-valent vaccine is scheduled to begin in 1998, Siber noted.
"The reason for the South African trial," Siber explained, "is that there are some rare types in the United States that are quite common in Africa, Asia and Latin America." And some pharmaceutical companies are heading toward 11-valent vaccines to ensure even wider coverage of pneumococcal diseases, Siber said.
Summing up the "evolution" of pneumococcal vaccines, Siber said the seven-valent vaccines are the initial generation, covering about 80% of the disease types in the United States; and between 50% and 70% outside the country. It covers types 4, 6B, 9V, 14, 18C, 19F and 23F.
The nine-valent "achieves global coverage of at least 75%," he noted, adding coverage for types 1 and 5. An 11-valent vaccine increases coverage to at least 80% globally, adding coverage of types 3 and 7F.
While the childhood vaccine is different from the adult version, Siber expects the conjugate vaccine to result in an 70% to 80% reduction in serious pneumococcal disease.
Although a vaccine to protect against RSV has not yet reached the field trial stage, progress is being made in developing a live-attenuated vaccine, Siber said.
A subunit RSV vaccine is also being developed. But there have been concerns that a subunit vaccine could enhance disease, he said. Those fears originated with an episode in the 1960s in which a killed virus was used.
"The most important advantage of a live attenuated vaccine is that it is unlikely to enhance subsequent natural infection, as was observed with early killed virus vaccines.
"The children who received [the killed vaccine] that had not had natural illness before were found in a subsequent RSV season to have more severe illness," he explained.
The strategy appears to be using a live attenuated vaccine that would offer primary exposure to the disease. "The evidence suggests that once you've had exposure, whether to a live vaccine or to natural infection, you can have a sub-subunit to boost [the immune system], without enhancing disease," he said.
Another approach he discussed is maternal immunization. "It's efficient to give the mother the vaccine, and she would transfer the antibody across the placenta," he said.
The potential addition of two more vaccines raises the issue of simplifying the administration of so many vaccines. Currently there are 11 licensed vaccines in routine use.
"I think it's a major issue and a major concern for us as manufacturers to work toward combinations that allow for reduced numbers of shots," he said.
"The ideal would be to put all the vaccines in one shot, but for technical and regulatory reasons that's a pretty tall order," he said.
An alternative strategy is to divide the vaccines into a two-shot regimen. One possibility would be a diphtheria-tetanus-pertussis based shot, and a second would be a pneumococcal-based shot.
Pneumococcal diseases and RSV are two of the World Health Organization's top five priority diseases for vaccine development, noted Siber.
For more information:
- Siber G. Where are we going next with pediatric immunization? Presented at the Pediatric Infectious Disease Conference. Sept. 16-19. Napa Valley, Calif.
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