The New World primate, Aotus nancymae, as a model for examining the immunogenicity of a prototype enterotoxigenic Escherichia coli subunit vaccine

Vaccine. 2006 May 1;24(18):3786-92. doi: 10.1016/j.vaccine.2005.07.029. Epub 2005 Aug 30.

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.

MeSH terms

  • Adjuvants, Immunologic
  • Administration, Intranasal
  • Animals
  • Antibodies, Bacterial / blood*
  • Antigens, Bacterial / administration & dosage
  • Antigens, Bacterial / adverse effects
  • Antigens, Bacterial / immunology
  • Aotidae*
  • Bacterial Toxins / administration & dosage
  • Bacterial Toxins / genetics
  • Bacterial Toxins / immunology
  • Blood Cell Count
  • Blood Chemical Analysis
  • Enterotoxins / administration & dosage
  • Enterotoxins / genetics
  • Enterotoxins / immunology
  • Escherichia coli / immunology*
  • Escherichia coli Infections / prevention & control
  • Escherichia coli Proteins / administration & dosage
  • Escherichia coli Proteins / adverse effects
  • Escherichia coli Proteins / genetics
  • Escherichia coli Proteins / immunology
  • Escherichia coli Vaccines / administration & dosage
  • Escherichia coli Vaccines / adverse effects
  • Escherichia coli Vaccines / immunology*
  • Female
  • Gastric Lavage
  • Immunoglobulin A / blood
  • Immunoglobulin G / blood
  • Lactic Acid
  • Male
  • Models, Animal*
  • Mutation
  • Polyglycolic Acid
  • Polylactic Acid-Polyglycolic Acid Copolymer
  • Polymers
  • Vaccines, Subunit / administration & dosage
  • Vaccines, Subunit / adverse effects
  • Vaccines, Subunit / immunology*

Substances

  • Adjuvants, Immunologic
  • Antibodies, Bacterial
  • Antigens, Bacterial
  • Bacterial Toxins
  • CS6 antigen, E coli
  • Enterotoxins
  • Escherichia coli Proteins
  • Escherichia coli Vaccines
  • Immunoglobulin A
  • Immunoglobulin G
  • Polymers
  • Vaccines, Subunit
  • heat-labile enterotoxin, E coli
  • Polylactic Acid-Polyglycolic Acid Copolymer
  • Polyglycolic Acid
  • Lactic Acid