An IgG1 titre to the F1 and V antigens correlates with protection against plague in the mouse model

The objective of this study was to identify an immunological correlate of p rotection for a two-component subunit vaccine for plague, using a mouse mod el. The components of the vaccine are the F1 and V antigens of the plague-c ausing organism, Yersinia pestis, which are coadsorbed to alhydrogel and ad ministered intramuscularly. The optimum molar ratio of the subunits was det ermined by keeping the dose-level of either subunit constant whilst varying the other and observing the effect on specific antibody titre. A two-fold molar excess of F1 to V, achieved by immunizing with 10 mu g of each antige n, resulted in optimum antibody titres. The dose of vaccine required to pro tect against an upper and lower subcutaneous challenge with Y. pestis was d etermined by administering doses in the range 10 mg F1 + 10 mu g V to 0.01 mu g F1 + 0.01 mu g V in a two-dose regimen. For animals immunized at the 1 -mu g dose level or higher with F1 + V, an increase in specific IgG1 titre was observed over the 8 months post-boost and they were fully protected aga inst a subcutaneous challenge with 10(5) colony-forming units (CFU) virulen t Y. pestis at this time point. However, immunization with 5 mu g or more o f each subunit was required to achieve protection against challenge with 10 (7) CFU Y. pestis. A new finding of this study is that the combined titre o f the IgG1 subclass, developed to F1 plus V, correlated significantly (P < 0.05) with protection. The titres of IgG1 in vaccinated mice which correlat ed with 90%, 50% and 10% protection have been determined and provide a usef ul model to predict vaccine efficacy in man.