Safety and Immunogenicity of an Oral Inactivated Whole-CellPseudomonas aeruginosaVaccine Administered to Healthy Human Subjects

Abstract

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 postvaccination. Following vaccination, several individuals were identified as antibody responders for all three immunoglobulin (Ig) isotypes tested, specifically against whole-cell P. aeruginosa extract and outer membrane proteins F and I. The mean pooled lipopolysaccharide antigen-specific IgA showed the most significant and constant increases in titer postdose, 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 postdose) in the presence of the postvaccination 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, hematology, 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 were serum IgA levels and that pooled sera collected postimmunization have an increased capacity to promote opsonophagocytotic killing of P. aeruginosa.

Mannose-modified chitosan microspheres enhance OprF-OprI-mediated protection of mice against Pseudomonas aeruginosa infection via induction of mucosal immunity

“…5a). Specific IgA antibodies elicited by mucosal immunization are likely to play an important part in the adaptive immune system by inhibiting adhesion and colonization of bacterial pathogens, such as P. aeruginosa (Cripps et al 2006;Krause et al 2011). FI-specific IgA titers in immune site nasal washes of FI-MCS-MP-treated mice were significantly higher with earlier peaks than those in mice that did not receive the mannose-modified version of the vaccine (Fig.…”

Protection against Pseudomonas aeruginosa lung infection in mice by recombinant OprF-pulsed dendritic cell immunization

“…Previous studies suggested that systemic immunity, from either oral vaccination [8] or i.p. vaccination [31] with P. aeruginosa vaccine constructs, was as effective as mucosal delivery of the vaccine in a mucosal challenge.…”

A randomized, placebo-controlled phase I study assessing the safety and immunogenicity of aPseudomonas aeruginosahybrid outer membrane protein OprF/I vaccine (IC43) in healthy volunteers

“…Although the results of several attempts to develop a vaccine have been published, no P. aeruginosa vaccine is available. 5,[8][9][10][11][12][13] In gram-negative bacteria lipopolysaccharides and outer membrane proteins are the major antigenic components of the bacterial envelope. Because lipopolysaccharide-based vaccines might cause systemic adverse reactions, 14 due to systemic inflammation after parenteral injection, 7 outer membrane protein-based vaccines with an acceptable toxicity profile are attractive clinical development candidates.…”