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The US measles epidemics of 1989-1991 included a series of outbreaks resulting from vaccine failure. A series of studies was launched aimed at elucidating the mechanisms of this vaccine failure. A meta-analysis of the literature examining epidemics in vaccinated populations was conducted, which showed that the secondary vaccine failure rate (development of the disease despite an initial or primary vaccine success) is no more than 0.2%. The overwhelming proportion of measles vaccine failure was due to primary vaccine failure (failure to ever generate antibody from antigenic stimulation). This comparison of two geographically distinct communities revealed that 10% of children previously vaccinated against measles lacked antibody on follow-up and that these vaccine failures clustered in families. A study of monozygotic and dizygotic twins revealed a high degree of heritability of measles vaccine antibody level. Subsequent studies found associations with both class I and class II alleles in these population-based studies. In the future, detection of the specific peptides that interact with human leukocyte antigen (HLA) molecules may serve as the basis for improved vaccines and address vaccine failure that results from coldchain problems, immaturity of the immune system, malnutrition and maternal immunity. [ABSTRACT FROM AUTHOR]

The incidence of influenza in children well exceeds that of the elderly and has been identified as the basis for 20% of doctor visits for children during the winter. The disease results in over 100 hospitalizations per 100 000 person-months in children <2 years of age. Furthermore, children serve as the major vector in the community; thus, influenza in children results in significant costs to society. Although efficacious, the current intramuscular, inactivated influenza vaccine is infrequently used in children, and is currently targeted only at children at high risk and those who are household members of such individuals. Experts believe that vaccinating only high risk individuals has little impact on the cycle of annual epidemics, but that universal vaccination of children may very well have a substantial impact. Experimental data support this. A recently published cost-benefit analysis indicated that routine, school-aged vaccination through individual visits to a clinician would save $US4 per child vaccinated. A group program such as a school-based one would save $US35. One obstacle to universal vaccination includes the real and perceived resistance to the addition of yet another annual injection to the already crowded schedule of routine childhood immunizations. Nearing licensure is an intranasal, live attenuated, cold-adapted intranasal influenza vaccine. Cold-adaptation prevents replication in the lower respiratory tract. Trials have demonstrated immunogenicity, safety, and tolerability in adults as well as children. Placebo-controlled trials have shown efficacy rates of 83 to 94%. This novel vaccine addresses obstacles to universal childhood immunization and would permit a program of routine use that would dramatically reduce transmission and stem epidemics of influenza. [ABSTRACT FROM AUTHOR]