Aerogenic BCG Vaccination Against Tuberculosis in Animal and Human Subjects

Abstract

Aerosol vaccination against tuberculosis is as old as the disease itself. There can be no question that T-irulent tubercle bacilli have been aspirated over the milleniums and have been a great factor in increasing our resistance against virulent tubercle bacilli. The danger, however, of aspirating virulent tubercle bacilli is that there is always the possibility of developing progressive disease; and furthermore, once a virulknt organism lodges in the body, it remains a constant source of danger to the host. It has been shown by Middlebrookl that as few as ten BCG organisms given by the aerosol route will induce in guinea pigs an immunity which is comparable to ten times that dose given subcutaneously or 100,000 times that dose given intradermally. The tuberculin conversion by the various routes of immunization was similar as was the reduction in number of challenge organisms (H37RV) in the lungs and spleens twenty-one days after the challenge as compared to nonvaccinated animals. Similar results demonstrating the superiority of the respiratory route over the percutaneous route have been obtained by Eigelsbach et aL2 in monkeys and guinea pigs with live tularemia vaccine. Aleskandrov et aL38 have obtained evidence of immunologic responses following aerosol vaccination of human subjects (agglutinins, opsono-phagocytic indices, complement fixation, skin test responses) for brucellosis, tuIaremia, anthrax and plague.There are numerous factors which determine the actual number of organisms aspirated int.0 the lower respiratory tract beyond the cilia and especially the terminal broiichioles when subjects are exposed to aerosols. Paramount in this consideration is particle size. Diagram 1 is a schematic representation of the anatomy of the pulmonary tree showing theoretic retention of particles relative to size, according to L a n d~i h l .~ Although there is not universal agreement as to particle size lodging in t,he bronchial tree, it is agreed by most that particles 30 microns in diameter and above are deposited mainly in the trachea. Particles from 1 to 6 microns in diameter reach the respiratory bronchioles and

Immunization by a bacterial aerosol

“…Our results compare favorably with the work of Rosenthal et al (17) and Lagranderie et al (18). In the pioneering work by Rosenthal et al in 1968 (17), guinea pigs, children, and medical students were exposed to BCG aerosols generated by nebulization.…”

Enhanced Immunogenicity and Protective Efficacy Against Mycobacterium tuberculosis of Bacille Calmette-Guérin Vaccine Using Mucosal Administration and Boosting with a Recombinant Modified Vaccinia Virus Ankara

“…They support M. tuberculosis challenge studies in macaques and guinea pigs that have shown aerosol administration of BCG to be more protective than parenteral (p.) vaccination (10,11). BCG has also been given as an aerosol to healthy adults and children and repeatedly to patients with metastatic lung disease (12)(13)(14). Respiratory function tests and postmortem examination of cancer patients administered BCG by aerosol indicated no significant pulmonary dysfunction or disseminated BCG infection (13,14).…”

Paucibacillary Tuberculosis in Mice after Prior Aerosol Immunization with Mycobacterium bovis BCG

“…Finally, BCG vaccination of human subjects by the respiratory route has been reported to be well tolerated and to result in tuberculin conversion in a majority of vaccines (18,19). While the potential for vaccination of humans by the respiratory route is unclear, it is worth emphasizing that mice immunized and challenged by the aerosol route exhibited an intense cellular response to the challenge that subsided during the 6 weeks after challenge.…”