Endpoint and epitope-specific antibody responses as correlates of vaccine-mediated protection of mice against ricin toxin
| Autor: | Jennifer Doering, Jennifer L. Yates, Nicholas J. Mantis, Oreola Donini, Dylan J. Ehrbar, Greta Van Slyke, Ellen S. Vitetta |
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| Rok vydání: | 2020 |
| Předmět: |
medicine.drug_class
030231 tropical medicine Ricin Monoclonal antibody Epitope Food and drug administration 03 medical and health sciences chemistry.chemical_compound Epitopes Mice 0302 clinical medicine Immunity Medicine Animals 030212 general & internal medicine General Veterinary General Immunology and Microbiology biology business.industry Public Health Environmental and Occupational Health Antibodies Monoclonal Antibodies Neutralizing Titer Specific antibody Ricin toxin Infectious Diseases chemistry Biotinylation Immunology Antibody Formation Vaccines Subunit biology.protein Molecular Medicine Antibody business |
| Zdroj: | Vaccine. 38(43) |
| ISSN: | 1873-2518 |
| Popis: | The successful licensure of vaccines for biodefense is contingent upon the availability of well-established correlates of protection (CoP) in at least two animal species that can then be applied to humans, without the need to assess efficacy in the clinic. In this report we describe a multivariate model that combines pre-challenge serum antibody endpoint titers (EPT) and values derived from an epitope profiling immune-competition capture (EPICC) assay as a predictor in mice of vaccine-mediated immunity against ricin toxin (RT), a Category B biothreat. EPICC is a modified competition ELISA in which serum samples from vaccinated mice were assessed for their ability to inhibit the capture of soluble, biotinylated (b)-RT by a panel of immobilized monoclonal antibodies (mAbs) directed against four immunodominant toxin-neutralizing regions on the enzymatic A chain (RTA) of RT. In a test cohort of mice (n=40) vaccinated with suboptimal doses of the RTA subunit vaccine, RiVax®, we identified two mAbs, PB10 and SyH7, which had EPICC inhibition values in pre-challenge serum samples that correlated with survival following a challenge with 10 x LD50of RT administered by intraperitoneal (IP) injection. Analysis of a larger cohort of mice (n=645) revealed that a multivariate model combining endpoint titers and an epitope-profiling immune-competition capture (EPICC) assay values for PB10 and SyH7 as predictive variables had significantly higher statistical power than any one of the independent variables alone. Establishing the correlates of vaccine-mediated protection in mice represents an important steppingstone in the development of RiVax®as a medical countermeasure under the United States Food and Drug Administration’s “Two Animal Rule.” |
| Databáze: | OpenAIRE |
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