Study to Determine the Safety and Immunogenicity of an Oral Inactivated Whole-cell Pseudomonas aeruginosa Vaccine Administered to Healthy Human Subjects

25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 This study examines the safety and immunogenicity of an oral, whole-cell Pseudomonas aeruginosa vaccine administered to healthy volunteers. Thirty subjects received an oral dose of Pseudostat in two timed, measured, doses with serological follow-up to 56 days post vaccinination. Following vaccination several individuals were identified as antibody responders for all three immunoglobulin isotypes tested, specifically against whole-cell P. aeruginosa extract and outer membrane proteins F and I. The mean pooled lipopolysaccharide (LPS) antigen specific IgA showed the most significant and constant increases in titer post dose, with a similar increase in titer for whole-cell P. aeruginosa extract specific IgA. The results demonstrated an increased phagocytic ability of the selected macrophage cell line in post vaccination sera. Furthermore a significant increase in intracellular macrophage killing of opsonized P. aeruginosa was also demonstrated (82% on Day 14 post dose) in the presence of the post vaccination sera. The safety component of the study did not show any vaccine-attributable adverse effects in any of the subjects as documented by clinical evidence, haematology and biochemistry profiles. We conclude that Pseudostat is safe and immunogenic in humans at this dose, and that further studies to determine the appropriate dosage and efficacy are needed. In our study, we have shown that the most significant and sustained responses to oral vaccination in human adult volunteers was serum IgA and that pooled sera collected post immunization has an increased capacity to promote opsonophagocytotic killing of P. aeruginosa.