The encapsulation of enterotoxigenic Escherichia coli colonization factor CS3 in biodegradable microspheres enhances the murine antibody response following intranasal administration

• Published in: Microbiology (Society for General Microbiology) Vol. 152; no. 3; pp. 779 - 786
• Main Authors: Byrd, Wyatt, Cassels, Frederick J
• Format: Journal Article
• Language: English
• Published: Reading Soc General Microbiol 01.03.2006; Society for General Microbiology
• Subjects: Adjuvants, Immunologic; Administration, Intranasal; Animals; Antibodies, Bacterial - analysis; Antibodies, Bacterial - blood; Bacteriology; Biological and medical sciences; Escherichia coli; Escherichia coli - immunology; Escherichia coli Proteins - administration & dosage; Escherichia coli Proteins - chemistry; Escherichia coli Proteins - immunology; Escherichia coli Vaccines - administration & dosage; Escherichia coli Vaccines - immunology; Female; Fimbriae Proteins - administration & dosage; Fimbriae Proteins - chemistry; Fimbriae Proteins - immunology; Fundamental and applied biological sciences. Psychology; Immunoglobulin E - analysis; Immunoglobulin E - blood; Lactic Acid; Mice; Mice, Inbred BALB C; Microbiology; Microspheres; Pathogenicity, virulence, toxins, bacteriocins, pyrogens, host-bacteria relations, miscellaneous strains; Polyglycolic Acid; Polylactic Acid-Polyglycolic Acid Copolymer; Polymers; Antigen; Encapsulation; Vertebrata; Mammalia; Immunogenicity; Mouse; Escherichia coli; Rodentia; Immunoblotting assay; Bacteria; ELISA assay; Enterobacteriaceae
• ISSN: 1350-0872; 1465-2080
• DOI: 10.1099/mic.0.28667-0

1 Department of Enteric Infections, Walter Reed Army Institute of Research, Silver Spring, MD 20910-7500, USA 2 18929 Fountain Hills Drive, Germantown, MD 20874, USA Correspondence Wyatt Byrd dagmarbyrd{at}comcast.net The aim of this study was to measure serum and mucosal antibody responses following intranasal administration of biodegradable poly( DL -lactide- co -glycolide) (PLGA) microspheres loaded with the CS3 colonization factor isolated from enterotoxigenic Escherichia coli (ETEC). The response was compared against that measured in mice similarly administered the native CS3 antigen and in mice co-administered, along with the CS3 antigen, a known mucosal adjuvant, the R192G mutant heat-labile enterotoxin (mLT). The integrity of the CS3 antigen released from the microspheres was maintained as determined by SDS-PAGE and immunoblotting. Native CS3 induced serum and mucosal (bronchoalveolar, small intestinal and faecal) IgG and IgA responses. The co-administration of the mLT mucosal adjuvant significantly enhanced ( P <0·001) serum and mucosal antibody responses to the CS3 protein. Likewise, the CS3-loaded PLGA microspheres induced significantly greater ( P <0·001) serum and mucosal antibody responses than native CS3, as well as inducing antibody responses superior to those of the CS3 plus mLT formulation. Following administration of CS3 plus mLT, the mice became distressed (loss of activity, increased huddling, ruffled fur), a situation not seen following administration of the CS3-loaded PLGA microspheres. The results in this trial show that the CS3-loaded PLGA microspheres when administered intranasally to mice caused no observable distress to the mice and significantly ( P <0·001) enhanced the immunogenicity of the CS3 protein. Abbreviations: BALT, bronchus-associated lymphoid tissue; BCA, bicinchoninic acid; ETEC, enterotoxigenic Escherichia coli ; GALT, gut-associated lymphoid tissue; MALT, mucosa-associated lymphoid tissue; mLT, mutant heat-labile enterotoxin (R192G); NALT, nasal-associated lymphoid tissue; PLGA, poly( DL -lactide- co -glycolide) microspheres; sIgA, secretory IgA