Anti-HFRS Human IgG Produced in Transchromosomic Bovines Has Potent Hantavirus Neutralizing Activity and Is Protective in Animal Models.

Autor: Perley CC; Virology Division, United States Army Medical Research Institute of Infectious Diseases, Frederick, MD, United States., Brocato RL; Virology Division, United States Army Medical Research Institute of Infectious Diseases, Frederick, MD, United States., Wu H; SAB Biotherapeutics Inc., Sioux Falls, SD, United States., Bausch C; SAB Biotherapeutics Inc., Sioux Falls, SD, United States., Karmali PP; Arcturus Therapeutics Inc., San Diego, CA, United States., Vega JB; Arcturus Therapeutics Inc., San Diego, CA, United States., Cohen MV; Virology Division, United States Army Medical Research Institute of Infectious Diseases, Frederick, MD, United States., Somerville B; Virology Division, United States Army Medical Research Institute of Infectious Diseases, Frederick, MD, United States., Kwilas SA; Virology Division, United States Army Medical Research Institute of Infectious Diseases, Frederick, MD, United States., Principe LM; Virology Division, United States Army Medical Research Institute of Infectious Diseases, Frederick, MD, United States., Shamblin J; Virology Division, United States Army Medical Research Institute of Infectious Diseases, Frederick, MD, United States., Chivukula P; Arcturus Therapeutics Inc., San Diego, CA, United States., Sullivan E; SAB Biotherapeutics Inc., Sioux Falls, SD, United States., Hooper JW; Virology Division, United States Army Medical Research Institute of Infectious Diseases, Frederick, MD, United States.
Jazyk: angličtina
Zdroj: Frontiers in microbiology [Front Microbiol] 2020 May 07; Vol. 11, pp. 832. Date of Electronic Publication: 2020 May 07 (Print Publication: 2020).
DOI: 10.3389/fmicb.2020.00832
Abstrakt: We explored an emerging technology to produce anti-Hantaan virus (HTNV) and anti-Puumala virus (PUUV) neutralizing antibodies for use as pre- or post-exposure prophylactics. The technology involves hyperimmunization of transchomosomic bovines (TcB) engineered to express human polyclonal IgG antibodies with HTNV and PUUV DNA vaccines encoding G n G c glycoproteins. For the anti-HTNV product, TcB was hyperimmunized with HTNV DNA plus adjuvant or HTNV DNA formulated using lipid nanoparticles (LNP). The LNP-formulated vaccine yielded fivefold higher neutralizing antibody titers using 10-fold less DNA. Human IgG purified from the LNP-formulated animal (SAB-159), had anti-HTNV neutralizing antibody titers >100,000. SAB-159 was capable of neutralizing pseudovirions with monoclonal antibody escape mutations in G n and G c demonstrating neutralization escape resistance. SAB-159 protected hamsters from HTNV infection when administered pre- or post-exposure, and limited HTNV infection in a marmoset model. An LNP-formulated PUUV DNA vaccine generated purified anti-PUUV IgG, SAB-159P, with a neutralizing antibody titer >600,000. As little as 0.33 mg/kg of SAB-159P protected hamsters against PUUV infection for pre-exposure and 10 mg/kg SAB-159P protected PUUV-infected hamsters post-exposure. These data demonstrate that DNA vaccines combined with the TcB-based manufacturing platform can be used to rapidly produce potent, human, polyclonal, escape-resistant anti-HTNV, and anti-PUUV neutralizing antibodies that are protective in animal models.
(Copyright © 2020 Perley, Brocato, Wu, Bausch, Karmali, Vega, Cohen, Somerville, Kwilas, Principe, Shamblin, Chivukula, Sullivan and Hooper.)
Databáze: MEDLINE
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