Potent Monoclonal Antibodies Against Circulating Yellow Fever Virus Strains from Donors Immunized with the 17D Vaccine.

Yellow fever (YF) causes approximately 50,000 deaths annually worldwide and is transmitted by infection with the yellow fever virus (YFV), which is endemic in Sub-Saharan Africa and tropical South America. The live-attenuated YFV 17D vaccine, developed in 1937, is essential to control YFV transmission, but the finite shelf life and manufacturing constraints of egg-based vaccine production, the rare but severe adverse events, and the lack of effective therapeutic options for YF disease highlight the need for new YFV vaccines and therapies. Potent YFV antibodies that neutralize circulating strains could be promising passive immunizations or treatments and guide nonreplicating YF vaccine development. In this study, we captured and screened natively paired heavy and light chain antibody libraries from two donors immunized with the YFV 17D vaccine. Yeast surface display libraries were generated and stained using YF virus-like particles purified by chromatographic techniques. Three anti-YFV antibodies were identified with potent neutralizing activity against circulating strains from Western Africa and South America, including one potent antibody with a neutralizing half-maximal inhibitory concentration of <5 ng/mL against the 17D vaccine strain. These new YFV antibodies have the potential to serve as YFV outbreak countermeasures for treatment or prevention and guide future vaccine efforts.