Journal Article

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

Espinoza, Nereyda, Scott, Daniel, Porter, Chad, Cassels, Frederick J., Luckett, Rickey, Tribble, David, Nunez, Gladys, Jones, Franca R., Savarino, Stephen J., Hall, Eric R., Meza, Rina, Salazar, Milagros

2006

Overview

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 μg; positive control), or intragastrically (IG) with meCS6 (200 or 1000 μg) with or without 2 μg LT(R192G) in three doses given at 2-week intervals. In a second experiment, A. nancymae were inoculated IG with 950 μg of meCS6 with or without 2 μg 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 μg meCS6 ( n = 14) had a serum IgG and IgA response, respectively, compared to only 28.6% of monkeys given 200 μg 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 μg meCS6 was more effective at eliciting an immune response than the four-dose, 48-h regimen with 950 μg meCS6. Results from this study indicate that A. nancymae provide a useful ETEC preclinical safety and immunogenicity model.

• Publisher: Elsevier Ltd,Elsevier
• Subject: Adjuvants, Immunologic / Administration, Intranasal / Animals / Antibodies, Bacterial - blood / Antigens, Bacterial - administration & dosage / Antigens, Bacterial - adverse effects / Antigens, Bacterial - immunology / Aotidae / Aotus nancymaee / Applied microbiology / Bacterial Toxins - administration & dosage / Bacterial Toxins - genetics / Bacterial Toxins - immunology / Bacteriology / Biological and medical sciences / Blood Cell Count / Blood Chemical Analysis / Enterotoxins - administration & dosage / Enterotoxins - genetics / Enterotoxins - immunology / Escherichia coli / 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 / Fundamental and applied biological sciences. Psychology / Gastric Lavage / Immunoglobulin A - blood / Immunoglobulin G - blood / Lactic Acid / Male / Microbiology / Miscellaneous / Models, Animal / Mutation / Polyglycolic Acid / Polylactic Acid-Polyglycolic Acid Copolymer / Polymers / Vaccines, antisera, therapeutical immunoglobulins and monoclonal antibodies (general aspects) / Vaccines, Subunit - administration & dosage / Vaccines, Subunit - adverse effects / Vaccines, Subunit - immunology