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.

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Publication Details

Journal
American Journal of Tropical Medicine and Hygiene
Published
2025-11-20
DOI
https://doi.org/10.4269/ajtmh.25-0057
Primary Topic
Mosquito-borne diseases and control
Type
article
Field-Weighted Citation Impact
0.00
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article

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

Farida Laboune, Morgan R. Timm, Danielle R. D. Saunders, Xiaoli Pan et al.
American Journal of Tropical Medicine and Hygiene
Mosquito-borne diseases and control
article

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

Farida Laboune, Morgan R. Timm, Danielle R. D. Saunders, Xiaoli Pan, Barney S. Graham, Dana L. Vanlandingham, Emily E. Coates, Erica Normandin, Túlio M. Lima, Leda R. Castilho, Jacy R. Wolfe, Theodore C. Pierson, Stephen Higgs, Katherine E. Burgomaster, Ahmed S. Fahad, Emilie Sanchez, Bharat Madan, Brandon J. DeKosky, Kimberly A. Dowd, Richard Kühn, John R. Mascola, Amy R. Henry, John Misasi, Matheus Oliveira de Souza, Yan-Jang S. Huang, Daniel C. Douek, Andrew Miller, Yuliya Petrova
article en

Abstract

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.

American Journal of Tropical Medicine and HygieneVol. 114(1)
Universidade Federal do Rio de Janeiro (BR), National Institutes of Health (US), University of Kansas (US), Kansas State University (US), SUNY Upstate Medical University (US), Purdue University West Lafayette (US), Ragon Institute of MGH, MIT and Harvard (US), National Institute of Allergy and Infectious Diseases (US), Laboratoire d'Excellence Canaux Ioniques d'Intérêt Thérapeutique (FR), United States Air Force Academy (US), Massachusetts Institute of Technology (US)
Openalex Percentile: Top 54%
Mosquito-borne diseases and control
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