Found at: doi:10.1371/journal.pone.0013350.s001 (0.05 MB DOC) Text S1 This is a simple version of our study findings for nonspecialists. Found at: doi:10.1371/journal.pone.0013350.s005 (0.03 MB DOC) Human Anti-Plague Monoclonal Antibodies Protect Mice from Yersinia pestis in a Bubonic Plague Model Yersinia pestis is the etiologic agent of plague that has killed more than 200 million people throughout the recorded history of mankind. Antibiotics may provide little immediate relief to patients who have a high bacteremia or to patients infected with an antibiotic resistant strain of plague. Two virulent factors of Y. pestis are the capsid F1 protein and the low-calcium response (Lcr) V-protein or V-antigen that have been proven to be the targets for both active and passive immunization. There are mouse monoclonal antibodies (mAbs) against the F1- and V-antigens that can passively protect mice in a murine model of plague; however, there are no anti-Yersinia pestis monoclonal antibodies available for prophylactic or therapeutic treatment in humans. We identified one anti-F1-specific human mAb (m252) and two anti-V-specific human mAb (m253, m254) by panning a naïve phage-displayed Fab library against the F1- and V-antigens. The Fabs were converted to IgG1s and their binding and protective activities were evaluated. M252 bound weakly to peptides located at the F1 N-terminus where a protective mouse anti-F1 mAb also binds. M253 bound strongly to a V-antigen peptide indicating a linear epitope; m254 did not bind to any peptide from a panel of 53 peptides suggesting that its epitope may be conformational. M252 showed better protection than m253 and m254 against a Y, pestis challenge in a plague mouse model. A synergistic effect was observed when the three antibodies were combined. Incomplete to complete protection was achieved when m252 was given at different times post-challenge. These antibodies can be further studied to determine their potential as therapeutics or prophylactics in Y. pestis infection in humans. Yersinia pestis (Y. pestis) is the causative agent of plague that has killed over an estimated 200 million people in previous pandemics [1] . The current incidence of plague is low but the animal reservoirs for Y. pestis exist worldwide. Sporadic cases have been reported recently with an average case number of 2,500 worldwide [2] . Y. pestis can be rendered airborne and its potential use as a bioweapon is recognized [3] as a category A agent on the NIAID list of biodefense-related pathogens. Current treatment for plague consists of antibiotics, while a live attenuated vaccine against plague is used in the former Soviet Union for prevention [4] . Nevertheless, these live attenuated whole-cell vaccines or killed whole-cell vaccines have adverse effects to varying degrees [4] . Though both types of treatment are efficacious, there is a need for an alternative treatment for plague [5] .