response and lower Th-2 response. A third possibility would be to delete a nonessential antigen from BCG in order to use that antigen, or its absence, as a diagnostic marker; this would be valuable in future trials of protective efficacy for any TB vaccine.
In response to questions from the audience, Dr. Hoft added the following points:
Efficacy studies show that BCG is more effective in infants than in adults, but this is partly because its easier to detect clinical effects in infants, who have a higher incidence of progressing to disseminated disease. Efficacy is harder to detect in vaccinated adults, who may take 10 or 20 years to progress to disseminated disease.
Rising rates of TB in adult populations, especially in tropical developing countries, do not point to a major failure in terms of BCG vaccination of adults. At the same time, they point to the need to do better. What is needed is a strategy that concentrates on preventing the spread of infection by detecting and treating asymptomatic as well as symptomatic cases.
Evidence suggests that Th-2 responses predominate in antibody production, while Th-1 responses induce Ig subsets. The two don’t necessarily conflict in the development of protective immunity, but it may be important to learn how to use different schedules of vaccination to induce the two responses in different sites.
As long as overall rates of infection remain low, the United States will probably not use BCG except for people who are at very high risk for infection with multiple-drug resistant TB.
There is data on crossreactive immune responses to other mycobacterial species such as M. vaccae. This may have a role as a potential adjuvant in immunotherapy. Further study is needed.
There are as yet no data on the use of BCG as a carrier for other antigens, but it promises to be a very useful vector. The technique has worked in animals, and MedImmune is currently conducting tests in humans.
There have at present been no controlled trials of intranasal or oral vaccination with BCG in humans.
Pathobiology. Histoplasma capsulatum and Coccidioides immitis are soil-based dimorphic fungi. In the soil they exist as molds, but they can cause serious disease when inhaled by animals or humans.