Safety and Immunogenicity of a Pseudomonas aeruginosa Hybrid Outer Membrane Protein F-I Vaccine in Human Volunteers

Abstract

A hybrid protein [Met-Ala-(His)6OprF190–342-OprI21–83] consisting of the mature outer membrane protein I (OprI) and amino acids 190 to 342 of OprF of Pseudomonas aeruginosa was expressed in Escherichia coli and purified by Ni2+ chelate-affinity chromatography. After safety and pyrogenicity evaluations in animals, four groups of eight adult human volunteers were vaccinated intramuscularly three times at 4-week intervals and revaccinated 6 months later with either 500, 100, 50, or 20 μg of OprF-OprI adsorbed onto A1(OH)3. All vaccinations were well tolerated. After the first vaccination, a significant rise of antibody titers against P. aeruginosaOprF and OprI was measured in volunteers receiving the 100- or the 500-μg dose. After the second vaccination, significant antibody titers were measured for all groups. Elevated antibody titers against OprF and OprI could still be measured 6 months after the third vaccination. The capacity of the elicited antibodies to promote complement binding and opsonization could be demonstrated by a C1q-binding assay and by the in vitro opsonophagocytic uptake ofP. aeruginosa bacteria. These data support the continued development of an OprF-OprI vaccine for use in humans.

Clinical study to assess the immunogenicity and safety of a recombinantPseudomonas aeruginosaOprF-OprI vaccine in burn patients

“…Jones et al [16] showed in a clinical trial with burn patients immunized with a polyvalent P. aeruginosa LPS-based, T-cell-independent vaccine that overall survival of patients can be improved by vaccination immediately after a burn. However, in our study and also in the previously published vaccination trial in burn patients with native OPRs [18,19] it was possible to induce a primary T-cell-dependent immune response towards the vaccine in this group of patients. The elicited immune response was comparable to the secondary immune response against tetanus toxoid ( Figs.…”

Mucosal vaccination with a recombinant OprF-I vaccine ofPseudomonas aeruginosain healthy volunteers: comparison of a systemic vs. a mucosal booster schedule

“…Three brief episodes of fever (38. 23 8.4 ‡C) 24 h after a vaccination were recorded. Blood tests and physical examinations of the nasal mucosa, the deltoid muscle and general examinations remained unremarkable throughout the study.…”

RGD capsid modification enhances mucosal protective immunity of a non-human primate adenovirus vector expressing Pseudomonas aeruginosa OprF

“…Despite advances in antimicrobial therapy, effective treatment and control of P. aeruginosa remains a persistent problem and a vaccine against P. aeruginosa would be a strategy to prevent infections with P. aeruginosa in immunocompetent susceptible patients [2][3][4][5]. Among various P. aeruginosa vaccine anti-gens, outer membrane protein F (OprF) has emerged as a viable candidate [2,[5][6][7][8][9]: (i) OprF is conserved antigenically in wild-type strains of P. aeruginosa [10]; (ii) OprF protein or DNA vaccines have been tested in animals and humans [11][12][13][14][15][16][17]; and (iii) OprF is involved in sensing of immune activation by binding to interferons (IFNs), which can be blocked effectively by vaccine-induced anti-OprF antibodies [18,19].…”