title: The New World primate, Aotus nancymae, as a model for examining the immunogenicity of a prototype enterotoxigenic Escherichia coli subunit vaccine.
abstract: The colonization factors (CF) of enterotoxigenic Escherichia coli (ETEC) are being targeted for inclusion in a multi-subunit ETEC vaccine. This study was designed to examine the preclinical safety and immunogenicity of CF CS6, encapsulated in a biodegradable poly(DL-lactide-co-glycolide) (meCS6), and administered in the presence or absence of a mutated heat-labile enterotoxin, LT(R192G), in the non-human primate, Aotus nancymae. A. nancymae were inoculated intranasally (IN) with meCS6 (200 microg; positive control), or intragastrically (IG) with meCS6 (200 or 1000 microg) with or without 2 microg LT(R192G) in three doses given at 2-week intervals. In a second experiment, A. nancymae were inoculated IG with 950 microg of meCS6 with or without 2 microg LT(R192G) in four doses given every 48 h. Blood was collected to assess anti-CS6 and -LT serum immunoglobulin G (IgG) and IgA responses and safety variables (complete blood count and chemistry). Safety parameters were unchanged from baseline following all vaccinations. In Experiment 1, a dose-related serologic response to CS6 was observed; 78.6 and 57.1% of monkeys given 1000 microg meCS6 (n = 14) had a serum IgG and IgA response, respectively, compared to only 28.6% of monkeys given 200 microg meCS6 (n = 14) with a serum IgG and IgA response. No significant effect on the number of responders or the magnitude of responses was observed with the addition of LT(R192G). The three-dose, 2-week regimen with 1000 microg meCS6 was more effective at eliciting an immune response than the four-dose, 48-h regimen with 950 microg meCS6. Results from this study indicate that A. nancymae provide a useful ETEC preclinical safety and immunogenicity model.
authors.affiliation: Bacterial Diseases Program, Naval Medical Research Center Detachment (NMRCD-Lima, Peru), NMRCD Unit 3800, APO, AA 34031, Peru. jonesf@nmrc.navy.mil
authors.forename: Franca R
authors.initials: FR
authors.lastname: Jones
authors.forename: Eric R
authors.initials: ER
authors.lastname: Hall
authors.forename: David
authors.initials: D
authors.lastname: Tribble
authors.forename: Stephen J
authors.initials: SJ
authors.lastname: Savarino
authors.forename: Frederick J
authors.initials: FJ
authors.lastname: Cassels
authors.forename: Chad
authors.initials: C
authors.lastname: Porter
authors.forename: Rina
authors.initials: R
authors.lastname: Meza
authors.forename: Gladys
authors.initials: G
authors.lastname: Nunez
authors.forename: Nereyda
authors.initials: N
authors.lastname: Espinoza
authors.forename: Milagros
authors.initials: M
authors.lastname: Salazar
authors.forename: Rickey
authors.initials: R
authors.lastname: Luckett
authors.forename: Daniel
authors.initials: D
authors.lastname: Scott
mesh_terms: D000276:Adjuvants, Immunologic; D000281:Administration, Intranasal; D000818:Animals; D000907:Antibodies, Bacterial / Q000097:blood*; D000942:Antigens, Bacterial / Q000008:administration & dosage / Q000009:adverse effects / Q000276:immunology; D016645:Aotidae; D001427:Bacterial Toxins / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology; D001772:Blood Cell Count; D001774:Blood Chemical Analysis; D004768:Enterotoxins / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology; D004926:Escherichia coli / Q000276:immunology*; D004927:Escherichia coli Infections / Q000517:prevention & control; D029968:Escherichia coli Proteins / Q000008:administration & dosage / Q000009:adverse effects / Q000235:genetics / Q000276:immunology; D022361:Escherichia coli Vaccines / Q000008:administration & dosage / Q000009:adverse effects / Q000276:immunology*; D005260:Female; D005751:Gastric Lavage; D007070:Immunoglobulin A / Q000097:blood; D007074:Immunoglobulin G / Q000097:blood; D019344:Lactic Acid; D008297:Male; D023421:Models, Animal; D009154:Mutation; D011100:Polyglycolic Acid; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011108:Polymers; D022223:Vaccines, Subunit / Q000008:administration & dosage / Q000009:adverse effects / Q000276:immunology*
chemical_list: D000276:Adjuvants, Immunologic; D000907:Antibodies, Bacterial; D000942:Antigens, Bacterial; D001427:Bacterial Toxins; C098406:CS6 antigen, E coli; D004768:Enterotoxins; D029968:Escherichia coli Proteins; D022361:Escherichia coli Vaccines; D007070:Immunoglobulin A; D007074:Immunoglobulin G; D011108:Polymers; D022223:Vaccines, Subunit; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D019344:Lactic Acid; C027538:heat-labile enterotoxin, E coli