Figure 2.

Schematic of Antibodies that target Y. pestis and are effective at ameliorating disease. Y. pestis is a Gram-negative bacterium that expresses multiple potential targets that have been exploited for the development of novel medical countermeasures. Antibodies generated by active vaccination or administered via passive immunization have been successful at protecting cell culture and animals from Y. pestis infection. These targets include The F1 capsular antigen (yellow structures depicted in the left panel) and the LcrV (V antigen) component of the T3SS injectisome. The capsule, while not absolutely necessary for virulence, has been the target of both vaccine and therapeutic strategies. The LcrV protein has been shown to be essential for virulence and has been a successful target in both active and passive immunization studies and is often combined with the F1 capsular antigen (i.e., the F1-V vaccine or mAb cocktail experiments). (Left Panel) In most cases, the Y. pestis bacterium will interact directly with host target cells via the T3SS injectisome and a robust anti-phagocytic capsule will also be present; thus, both anti-F1 and anti-V antibodies are potentially effective. (Right Panel) Non-encapsulated strains of Y. pestis can be found in nature or engineered in the laboratory. In cases of infection caused by non-encapsulated Y. pestis, the antibodies to the F1 capsular antigen are no longer effective and the protective immune response generated by a vaccine or the effective therapeutic mAb relies solely on the anti-V antibodies. A lipopolysaccharide structure (LPS) often observed in Y. pestis grown at 37 °C is depicted in blue in both panels. Other protective antigens have been identified and other novel antigen targets will almost certainly be identified in ongoing research efforts.