ABSTRACT
A recombinant fusion protein composed of Yersinia pestis fraction 1 capsule (F1) and virulence-associated V antigen (V) (F1-V) has been developed as the next-generation vaccine against plague. In this study, female Swiss Webster mice received a single intramuscular vaccination with one of eight doses of the F1-V vaccine and exposed 4 weeks later to either Y. pestis CO92 or C12 organisms by the subcutaneous or aerosol routes of infection. Quantitative anti-F1 and anti-V immunoglobulin G (IgG) ELISAs were used to examine the relationship between survival outcome and antibody titers to F1 and V. Results suggested that each 1log(10) increase in week 4 quantitative anti-F1 and anti-V IgG ELISA titers were associated with a 1.7-fold (p=0.0051) and 2.5-fold (p=0.0054) increase in odds of survival, respectively, against either bubonic or pneumonic plague and may serve as serological correlates of protection.
Subject(s)
Antibodies, Bacterial/blood , Antigens, Bacterial/immunology , Bacterial Proteins/immunology , Enzyme-Linked Immunosorbent Assay/methods , Plague/prevention & control , Pore Forming Cytotoxic Proteins/immunology , Yersinia pestis/immunology , Animals , Biomarkers , Female , Immunoglobulin G/blood , Mice , Recombinant Fusion Proteins/immunology , Survival AnalysisABSTRACT
Quantitative anti-F1 and anti-V IgG enzyme-linked immunosorbent assays (ELISAs) were developed to measure the serological response of female Swiss Webster mice after vaccination with the recombinant fusion protein, rF1-V, which is being developed as a plague vaccine. Several fundamental parameters of the ELISA were evaluated: specificity, precision, accuracy, and stability. Experimental results suggested that a potency assay based upon the serological response of female Swiss Webster mice, as measured by quantitative anti-F1 IgG and anti-V IgG ELISAs, might be used to evaluate the rF1-V fusion protein vaccine.
