Therapeutic administration of a cross-reactive mAb targeting the fusion glycoprotein of Nipah virus protects nonhuman primates.

Autor: Zeitlin L; Mapp Biopharmaceutical, San Diego, CA 92121, USA., Cross RW; Department of Microbiology and Immunology, University of Texas Medical Branch, Galveston National Laboratory, Galveston, TX 77550, USA., Woolsey C; Department of Microbiology and Immunology, University of Texas Medical Branch, Galveston National Laboratory, Galveston, TX 77550, USA., West BR; Mapp Biopharmaceutical, San Diego, CA 92121, USA., Borisevich V; Department of Microbiology and Immunology, University of Texas Medical Branch, Galveston National Laboratory, Galveston, TX 77550, USA., Agans KN; Department of Microbiology and Immunology, University of Texas Medical Branch, Galveston National Laboratory, Galveston, TX 77550, USA., Prasad AN; Department of Microbiology and Immunology, University of Texas Medical Branch, Galveston National Laboratory, Galveston, TX 77550, USA., Deer DJ; Department of Microbiology and Immunology, University of Texas Medical Branch, Galveston National Laboratory, Galveston, TX 77550, USA., Stuart L; Mapp Biopharmaceutical, San Diego, CA 92121, USA., McCavitt-Malvido M; Mapp Biopharmaceutical, San Diego, CA 92121, USA., Kim DH; Mapp Biopharmaceutical, San Diego, CA 92121, USA., Pettitt J; Mapp Biopharmaceutical, San Diego, CA 92121, USA., Crowe JE Jr; Department of Pathology, Microbiology and Immunology, Vanderbilt University Medical Center, Nashville, TN 37232, USA.; Vanderbilt Vaccine Center, Vanderbilt University Medical Center, Nashville, TN 37232, USA.; Department of Pediatrics, Vanderbilt University Medical Center, Nashville, TN 37232, USA., Whaley KJ; Mapp Biopharmaceutical, San Diego, CA 92121, USA., Veesler D; Department of Biochemistry, University of Washington, Seattle, WA 98195, USA.; Howard Hughes Medical Institute, Seattle, WA 98195, USA., Dimitrov A; Department of Microbiology and Immunology, Uniformed Services University, Bethesda, MD 20814, USA.; Henry M. Jackson Foundation for the Advancement of Military Medicine Inc., Bethesda, MD 20814, USA., Abelson DM; Mapp Biopharmaceutical, San Diego, CA 92121, USA., Geisbert TW; Department of Microbiology and Immunology, University of Texas Medical Branch, Galveston National Laboratory, Galveston, TX 77550, USA., Broder CC; Department of Microbiology and Immunology, Uniformed Services University, Bethesda, MD 20814, USA.
Jazyk: angličtina
Zdroj: Science translational medicine [Sci Transl Med] 2024 Apr 03; Vol. 16 (741), pp. eadl2055. Date of Electronic Publication: 2024 Apr 03.
DOI: 10.1126/scitranslmed.adl2055
Abstrakt: No licensed vaccines or therapies exist for patients infected with Nipah virus (NiV), although an experimental human monoclonal antibody (mAb) cross-reactive to the NiV and Hendra virus (HeV) G glycoprotein, m102.4, has been tested in a phase 1 trial and has been provided under compassionate use for both HeV and NiV exposures. NiV is a highly pathogenic zoonotic paramyxovirus causing regular outbreaks in humans and animals in South and Southeast Asia. The mortality rate of NiV infection in humans ranges from 40% to more than 90%, making it a substantial public health concern. The NiV G glycoprotein mediates host cell attachment, and the F glycoprotein facilitates membrane fusion and infection. We hypothesized that a mAb against the prefusion conformation of the F glycoprotein may confer better protection than m102.4. To test this, two potent neutralizing mAbs against NiV F protein, hu1F5 and hu12B2, were compared in a hamster model. Hu1F5 provided superior protection to hu12B2 and was selected for comparison with m102.4 for the ability to protect African green monkeys (AGMs) from a stringent NiV challenge. AGMs were exposed intranasally to the Bangladesh strain of NiV and treated 5 days after exposure with either mAb (25 milligrams per kilogram). Whereas only one of six AGMs treated with m102.4 survived until the study end point, all six AGMs treated with hu1F5 were protected. Furthermore, a reduced 10 milligrams per kilogram dose of hu1F5 also provided complete protection against NiV challenge, supporting the upcoming clinical advancement of this mAb for postexposure prophylaxis and therapy.
Databáze: MEDLINE