Therapeutic efficacy of an E coli strain carrying an ovalbumin allergenic peptide as a fused protein to OMPC in a murine model of allergic airway inflammation.
An Escherichia coli strain expressing the ovalbumin (OVA) 323-329 allergenic peptide on the bacterial surface was evaluated for its ability to reduce the lung inflammatory response in mice allergic to OVA. BALB/c mice were rendered allergic by means of two intraperitoneal injections of OVA suspended in alum 5 days apart, and one intratracheal boost 1 week later. The mice were then treated with two intranasal, 1 week apart, doses of 4x10(9) E. coli-UH302 transformed with plasmids pST13 or pST13-OVA(323-339), which bear the OmpC porin from Salmonella enterica serovar Typhi or the OmpC with the OVA allergenic 323-339 amino acid sequence inserted in the external loop 5. The allergic inflammatory reaction was evaluated on day 31, finding that mice treated with E. coli-UH302-pST13-OVA reduced four to seven times perivascular and peribronchial infiltrates, mucus production, goblet cell hyperplasia and eosinophils when compared with mice treated with E. coli-UH302-pST13 or saline solution. These results were consistent with a significant decrease of IL-5 mRNA and induction of IFN-gamma mRNA in cells from bronchio-alveolar lavages (BAL). Specific serum IgE anti-OVA was also reduced, although the decrease did not reach statistical significance. These results demonstrate that the bacterial live vector bearing an allergenic peptide successfully moderated two important components of allergy, pulmonary inflammation and mucus overproduction.
Yépez
Sara Huerta
SH
Unidad de Investigación Médica en Inmunología e Infectologi;a, Hospital de Infectología "Dr Daniel Méndez Hernández" Centro Médico "La Raza" IMSS, Apartado Postal 15-095, Mexico City, DF 02990, Mexico.
Pando
Rogelio Hernández
RH
Argumedo
Leopoldo Santos
LS
Paredes
Mario Vega
MV
Cueto
Angeles Hernández
AH
Isibasi
Armando
A
Bonilla
César R González
CR
D000485:Allergens / Q000276:immunology*; D000818:Animals; D001425:Bacterial Outer Membrane Proteins / Q000276:immunology*; D001992:Bronchoalveolar Lavage Fluid / Q000276:immunology; D016207:Cytokines / Q000096:biosynthesis; D004804:Eosinophils / Q000276:immunology; D004926:Escherichia coli / Q000235:genetics / Q000276:immunology*; D007073:Immunoglobulin E / Q000096:biosynthesis; D007249:Inflammation / Q000276:immunology*; D007371:Interferon-gamma / Q000096:biosynthesis; D015848:Interleukin-5 / Q000096:biosynthesis; D008168:Lung / Q000276:immunology; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D010047:Ovalbumin / Q000276:immunology*; D010455:Peptides / Q000276:immunology*; D010957:Plasmids / Q000235:genetics / Q000276:immunology; D018272:Porins / Q000276:immunology*; D012333:RNA, Messenger / Q000096:biosynthesis; D012130:Respiratory Hypersensitivity / Q000276:immunology*; D020133:Reverse Transcriptase Polymerase Chain Reaction
D000485:Allergens; D001425:Bacterial Outer Membrane Proteins; D016207:Cytokines; D015848:Interleukin-5; C113724:OmpC protein; D010455:Peptides; D018272:Porins; D012333:RNA, Messenger; D007073:Immunoglobulin E; D007371:Interferon-gamma; D010047:Ovalbumin