Inhalative vaccination with pneumococcal polysaccharide in healthy volunteers

In order to determine the feasibility of inhalative vaccination with polysaccharide antigen, we used controlled inhalation of a defined dose of Pneumovax in a randomized 3-arm study. The vaccine was either deposited in the alveoli (alveolar vaccination) or in the large airways (bronchial vaccination) and this was compared to standard intra-muscular vaccination. Adverse effects were minor and never exceeded WHO grade 2. There was frequent cough in the inhalative groups and frequent local pain at the injection site in the intra-muscular group. Specific serum IgG antibody measured before, and 4 and 12 weeks after, vaccination showed a greater than 2-fold rise in 4 out of 10 individuals after alveolar vaccination and in 6 out of 10 individuals after bronchial vaccination as compared to 10 out of 10 in the intra-muscular vaccination group. Average antibody levels of responders at 12 weeks were 350 microg/ml for alveolar vaccination, 200 microg/ml for bronchial vaccination and 1010 microg/ml for standard intra-muscular vaccination. Analysis of antibodies for 9 specific serotypes showed a more than 3-fold rise to 7-9 of the serotypes in the intra-muscular group. In both the bronchial and the alveolar group, all subjects responded but this was restricted to 2-4 of the 9 serotypes. The data show that polysaccharide vaccine can be safely administered by controlled inhalation and that it can induce good, albeit lower, serum antibody responses.