Long-term systemic and mucosal antibody responses measured in BALB/c mice following intranasal challenge with viable enterotoxigenic Escherichia coli.
The immunogenicity induced in BALB/c mice following intranasal challenge with a viable nonlethal dose (1.2 x 10(8) CFU) of enterotoxigenic Escherichia coli (ETEC) strain E23477A (O139:H28:CS1:CS3:LT+:ST+) was studied over a 140-day period. Serum IgG and IgM antibodies against coli surface antigen 3 (CS3), O139 lipopolysaccharide and heat-labile enterotoxin were measured by day 14 and remained at elevated levels out to day 140. The serum IgG response to the somatic antigens (CS3 and O139 lipopolysaccharide) was significantly greater (P < 0.05) than the IgG response to heat-labile enterotoxin, and the serum IgG response to CS3 was significantly greater (P < 0.05) than the IgG response to O139 lipopolysaccharide. The predominant serum IgG subclasses to CS3 were IgG1 and IgG2a, and they were significantly greater (P < 0.05) than IgG2b and IgG3. The predominant serum IgG subclass response to O139 lipopolysaccharide was initially IgG3 until day 56, after which IgG1 was predominant. The serum subclass response to CS3 indicated a mixed T helper 1/2 (Th1/Th2) profile, whereas the response to O139 lipopolysaccharide was primarily that of a Th2-type, at least over time. Fecal IgG and IgA responses to CS3 and O139 lipopolysaccharide were detected by day 14 and were measured out to day 140, with the CS3 fecal antibody responses being significantly greater (P < 0.05) than the O139 lipopolysaccharide and heat-labile enterotoxin fecal antibody responses. The aim of this study is the development of the intranasal mouse model that can aid in better understanding the immunopathology of ETEC infection and in screening of vaccine candidates prior to volunteer trials.
Department of Enteric Infections, Walter Reed Army Institute of Research, Silver Spring, MD, USA. dagmarbyrd@comcast.net
Wyatt
W
Byrd
Frederick J
FJ
Cassels
D000281:Administration, Intranasal; D000818:Animals; D000907:Antibodies, Bacterial / Q000032:analysis / Q000097:blood*; D001427:Bacterial Toxins / Q000276:immunology* / Q000378:metabolism; D004768:Enterotoxins / Q000276:immunology* / Q000378:metabolism; D004926:Escherichia coli / Q000276:immunology / Q000472:pathogenicity*; D004927:Escherichia coli Infections / Q000276:immunology* / Q000382:microbiology; D029968:Escherichia coli Proteins / Q000276:immunology* / Q000378:metabolism; D005243:Feces; D005260:Female; D036781:Fimbriae Proteins / Q000276:immunology; D006801:Humans; D008070:Lipopolysaccharides / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D009092:Mucous Membrane / Q000276:immunology*; D013997:Time Factors
D000907:Antibodies, Bacterial; D001427:Bacterial Toxins; D004768:Enterotoxins; D029968:Escherichia coli Proteins; D008070:Lipopolysaccharides; C081391:nfaE protein, E coli; D036781:Fimbriae Proteins; C027538:heat-labile enterotoxin, E coli