The Development of Moleculary Pure Antibody Reagents to Variant

PRINCIPAL INVESTIGATOR: Slack, John H. AWARDEE ORGANIZATION: Integrated Biotechnology Corp. 11711 North College Ave., Suite 196 Carmel, IN 46032 TELEPHONE NUMBER: (317) 575-7250 AWARDEE NUMBER: 200-93-0669 Measles virus, a severe acute highly contagious human pathogen, is not only responsible for clinical measles, but also for persistent central nervous system disease. In the United States, with the introduction of measles vaccine in 1963, the incidence of disease diminished from 200,000 to 400,000 cases annually to a low 1,497 cases in 1983. Following 1983, however, the number of cases of measles has rebounded to more than 60,000 cases and 100 associated deaths from 1989 to 1991. In less developed countries, measles remains a leading cause of child mortality causing about 2 million deaths per year. Some of the persistence of measles, in underdeveloped countries in particular, can be attributed to the failure to vaccinate key populations. Interestingly, in the United States, while approximately half of the recent measles cases occur in unvaccinated preschool populations, the remaining 50% involved those which were previously vaccinated. The rather simple explanations for measles resurgence, such as absence of vaccine administration or vaccine failures may not account for all increased measled disease. Therefore, other possible explanations such as the occurrence of antigenic variants of measles virus that evade conventional vaccine immunity are proposed as a basis for recent measles disease (Rota et al, 1992). Indeed, the genetic variability reported in current wild-type measles does occur in genes encoding fusion (F) and hemagglutinin (H) surface proteins whose functions are critical to virus pathogenesis. To this date, however, studies that might associate such variant strains to resurgent measles disease have not been done primarily due to the paucity of variant measles virus specific antibody reagents. Therefore, it is the objective of this Phase I proposal, in a collaborative arrangement with CDC, to make polyclonal or monoclonal antibodies to current wild-type disease associated measles virus or virus derived antigens.