Protective outcomes of high-affinity monoclonal antibodies against drug-resistant plague strains

Yersinia pestis, a category A infectious organism, is known to cause bubonic, septicemic, and pneumonic plague. With the emergence of streptomycin-resistant strains, there is an urgent need for new therapeutic strategies that can protect populations from Y. pestis infection. The main strategy for developing vaccines and therapeutic antibodies involves F1 antigen. Previous research has demonstrated that both human and murine monoclonal antibodies(mAbs) confer protective effects against Y. pestis infection. While, no relevant studies were identified on mAbs against drug-resistance Y. pestis.

Here, we constructed an antibody library from Y. pestis vaccine strain EV76-immunized mice by phage display. The mAbs were baited by recombinant F1 antigen, and the biological functions of the obtained mAbs were assessed and evaluated in plague-challenged mice.

For the Y. pestis strain 141 group, both Fm3 and Fm25 provided 100% protection at a dose of 100 µg. At 20 µg, only Fm3 conferred partial protection, with a survival rate of 25%, whereas all mice in the 4 µg treatment groups succumbed to infection within approximately 10 days. Against the drug-resistant Y. pestis strain S19960127, Fm25 at 100 µg resulted in complete survival, whereas Fm3 at the same dose conferred 75% protection. Neither mAbs showed protective efficacy at 20 µg or 4 µg, and all animals dying within approximately 10 days post-infection.

These findings indicated that mAbs Fm3 and Fm25 confer protection against virulent and drug-resistant strains of Y. pestis.