VACCINATION WITH THE F1 CAPSULE ANTIGEN OF Y. PESTIS ENDOWS RAPID ONSET OF PROTECTION AGAINST PLAGUE INFECTION, MEDIATED BY B1 CELLS

Yersinia pestis is the causative agent of plague, a fatal disease characterized by high mortality rates in untreated individuals. An anti-plague vaccine composed of the F1 and LcrV antigens is currently under clinical evaluation trials. Yet, in most of the studies that evaluated the vaccine’s efficacy, prolonged immunization regimes were applied. In the present study we assessed, using the mouse bubonic plague model, the ability of such vaccine to endow protection shortly after immunization and examined the traits enabling this rapid onset of anti-plague immunity.

Mice vaccinated with F1 and LcrV one day prior to a lethal Y. pestis challenge were effectively protected. Evaluation of the individual contribution of each vaccine component to this highly rapid protective response revealed that immunity is essentially mediated by F1 rather than LcrV. By using knock-out mouse strains lacking distinct classes of lymphocytes (microMT, deltaCD4), we found that B cells were absolutely required for F1-mediated rapid onset of protection, whereas the assisting activity of CD4 T helper cells was dispensable. These observations suggest the involvement of innate-like B1 cells in the early onset of protection. This suggestive involvement was examined in Btk^m/Xid mutant mouse strain that is defective in the ability to mount a serological response against T cell-independent (TI) antigens. While wild-type mice vaccinated with F1 several days prior to challenge were protected Xid mice were not, indicating that B1 cells play an essential role in eliciting F1-mediated rapid and effective anti-plague immunity. Flow cytometry analysis performed a day after vaccination with labeled-F1 demonstrated the induction of F1-binding peritoneal B1a cells. This study demonstrates for the first time the involvement of B1a cells in the rapid induction of anti-plague immunity by F1.