Preclinical evaluation of a fully-human, quadrivalent-hantavirus polyclonal antibody derived from non-human source.
Background: Hantaviruses are rodent-borne viruses that can cause severe disease in infected humans. In the New World, major hantaviruses include Andes virus (ANDV) and Sin Nombre virus (SNV), and the disease is known as hantavirus pulmonary syndrome (HPS). In the Old World, major hantaviruses includ...
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Elsevier
2025-03-01
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| Series: | International Journal of Infectious Diseases |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S120197122400523X |
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| author | Dr Jay Hooper Dr Steve Kwilas Dr Rebecca Brocato Mr. Matthew Josleyn Ms. Lucia Principe Mr Joshua Shamblin Dr. Hua Wu Dr. Christoph Bausch Dr. Tom Luke Dr Priya Karmali Mr. Jerel Vega Dr Padmanabh Chivukaula Dr. Eddie Sullivan |
| author_facet | Dr Jay Hooper Dr Steve Kwilas Dr Rebecca Brocato Mr. Matthew Josleyn Ms. Lucia Principe Mr Joshua Shamblin Dr. Hua Wu Dr. Christoph Bausch Dr. Tom Luke Dr Priya Karmali Mr. Jerel Vega Dr Padmanabh Chivukaula Dr. Eddie Sullivan |
| author_sort | Dr Jay Hooper |
| collection | DOAJ |
| description | Background: Hantaviruses are rodent-borne viruses that can cause severe disease in infected humans. In the New World, major hantaviruses include Andes virus (ANDV) and Sin Nombre virus (SNV), and the disease is known as hantavirus pulmonary syndrome (HPS). In the Old World, major hantaviruses include Hantaan virus (HTNV) and Puumala virus (PUUV), and the disease is known as hemorrhagic fever with renal syndrome (HFRS). Previously, transchromsomic bovines (TcBs) were used and engineered to produce fully human antibodies to produce anti-HPS human polyclonal neutralizing antibody (SAB-400) that protected Syrian hamsters against lethal disease caused by ANDV and SNV; and anti-HFRS human polyclonal neutralizing antibody, SAB-159 and SAB-159P, that protected hamsters against infection with HTNV and PUUV, respectively. Methods & Materials: Here, the same approach was used to produce a candidate cGMP product (SAB-163) targeting both HFRS and HPS. Two TcB animals were produced and qualified for cGMP antibody manufacturing. One animal was vaccinated with a lipid nanoparticle (LNP)-formulated ANDV and a SNV M gene-based DNA vaccine and a second animal was vaccinated with LNP-formulated HTNV and PUUV DNA vaccine. The hantavirus M gene encodes the viral envelop glycoproteins. The resultant fully-human, polyclonal antibody purified from the combined plasma from the two TcBs was designated SAB-163. Results: SAB-163 has potent neutralizing antibodies (PRNT50 >200,000) against the four targeted hantaviruses, and cross-neutralization against several other heterotypic hantaviruses, albeit with lower titers. SAB-163 was tested for safety in a GLP toxicity study in rabbits and human tissue binding study and was found to be safe. SAB-163 was tested for efficacy in Syrian hamsters. At a dosage of 10 mg/kg, SAB-163 is bioavailable in hamsters out to 70 days post-treatment with a half-life of 10-15 days. At this same dosage, SAB-163 administered 1 day or out 5 days after exposure protected all hamsters from lethal disease caused by ANDV. At a higher dose, partial protection was achieved as late as day 6 in the ANDV model. SAB-163 also protected hamsters in the HTNV, PUUV, and SNV infection models when administered 1 day before or up to 3 days after challenge. Conclusion: The candidate product is attractive because it is fully-human, polyclonal, safe and effective in animal models, and was produced from plasma collected within ∼100 days without the use of blood products from HFRS or HPS patients. Essentially, the virus sequence information was transformed into a candidate human polyclonal antibody product capable of protecting against prototype hantaviruses from Asia, Europe, and the Americas. |
| format | Article |
| id | doaj-art-23c67f4ecd494b9ab914639aae9100e2 |
| institution | OA Journals |
| issn | 1201-9712 |
| language | English |
| publishDate | 2025-03-01 |
| publisher | Elsevier |
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| series | International Journal of Infectious Diseases |
| spelling | doaj-art-23c67f4ecd494b9ab914639aae9100e22025-08-20T02:00:43ZengElsevierInternational Journal of Infectious Diseases1201-97122025-03-0115210744810.1016/j.ijid.2024.107448Preclinical evaluation of a fully-human, quadrivalent-hantavirus polyclonal antibody derived from non-human source.Dr Jay Hooper0Dr Steve Kwilas1Dr Rebecca Brocato2Mr. Matthew Josleyn3Ms. Lucia Principe4Mr Joshua Shamblin5Dr. Hua Wu6Dr. Christoph Bausch7Dr. Tom Luke8Dr Priya Karmali9Mr. Jerel Vega10Dr Padmanabh Chivukaula11Dr. Eddie Sullivan12USAMRIID, Fort Detrick, United StatesUSAMRIID, Fort Detrick, United StatesUSAMRIID, Fort Detrick, United StatesUSAMRIID, Fort Detrick, United StatesUSAMRIID, Fort Detrick, United StatesUSAMRIID, Fort Detrick, United StatesSAB Biotherapeutics, Sioux Falls, SD, United StatesSAB Biotherapeutics, Sioux Falls, SD, United StatesSAB Biotherapeutics, Sioux Falls, SD, United StatesArcturus Therapeutics, San Diego, CA, United StatesArcturus Therapeutics, San Diego, CA, United StatesArcturus Therapeutics, San Diego, CA, United StatesSAB Biotherapeutics, Sioux Falls, SD, United StatesBackground: Hantaviruses are rodent-borne viruses that can cause severe disease in infected humans. In the New World, major hantaviruses include Andes virus (ANDV) and Sin Nombre virus (SNV), and the disease is known as hantavirus pulmonary syndrome (HPS). In the Old World, major hantaviruses include Hantaan virus (HTNV) and Puumala virus (PUUV), and the disease is known as hemorrhagic fever with renal syndrome (HFRS). Previously, transchromsomic bovines (TcBs) were used and engineered to produce fully human antibodies to produce anti-HPS human polyclonal neutralizing antibody (SAB-400) that protected Syrian hamsters against lethal disease caused by ANDV and SNV; and anti-HFRS human polyclonal neutralizing antibody, SAB-159 and SAB-159P, that protected hamsters against infection with HTNV and PUUV, respectively. Methods & Materials: Here, the same approach was used to produce a candidate cGMP product (SAB-163) targeting both HFRS and HPS. Two TcB animals were produced and qualified for cGMP antibody manufacturing. One animal was vaccinated with a lipid nanoparticle (LNP)-formulated ANDV and a SNV M gene-based DNA vaccine and a second animal was vaccinated with LNP-formulated HTNV and PUUV DNA vaccine. The hantavirus M gene encodes the viral envelop glycoproteins. The resultant fully-human, polyclonal antibody purified from the combined plasma from the two TcBs was designated SAB-163. Results: SAB-163 has potent neutralizing antibodies (PRNT50 >200,000) against the four targeted hantaviruses, and cross-neutralization against several other heterotypic hantaviruses, albeit with lower titers. SAB-163 was tested for safety in a GLP toxicity study in rabbits and human tissue binding study and was found to be safe. SAB-163 was tested for efficacy in Syrian hamsters. At a dosage of 10 mg/kg, SAB-163 is bioavailable in hamsters out to 70 days post-treatment with a half-life of 10-15 days. At this same dosage, SAB-163 administered 1 day or out 5 days after exposure protected all hamsters from lethal disease caused by ANDV. At a higher dose, partial protection was achieved as late as day 6 in the ANDV model. SAB-163 also protected hamsters in the HTNV, PUUV, and SNV infection models when administered 1 day before or up to 3 days after challenge. Conclusion: The candidate product is attractive because it is fully-human, polyclonal, safe and effective in animal models, and was produced from plasma collected within ∼100 days without the use of blood products from HFRS or HPS patients. Essentially, the virus sequence information was transformed into a candidate human polyclonal antibody product capable of protecting against prototype hantaviruses from Asia, Europe, and the Americas.http://www.sciencedirect.com/science/article/pii/S120197122400523X |
| spellingShingle | Dr Jay Hooper Dr Steve Kwilas Dr Rebecca Brocato Mr. Matthew Josleyn Ms. Lucia Principe Mr Joshua Shamblin Dr. Hua Wu Dr. Christoph Bausch Dr. Tom Luke Dr Priya Karmali Mr. Jerel Vega Dr Padmanabh Chivukaula Dr. Eddie Sullivan Preclinical evaluation of a fully-human, quadrivalent-hantavirus polyclonal antibody derived from non-human source. International Journal of Infectious Diseases |
| title | Preclinical evaluation of a fully-human, quadrivalent-hantavirus polyclonal antibody derived from non-human source. |
| title_full | Preclinical evaluation of a fully-human, quadrivalent-hantavirus polyclonal antibody derived from non-human source. |
| title_fullStr | Preclinical evaluation of a fully-human, quadrivalent-hantavirus polyclonal antibody derived from non-human source. |
| title_full_unstemmed | Preclinical evaluation of a fully-human, quadrivalent-hantavirus polyclonal antibody derived from non-human source. |
| title_short | Preclinical evaluation of a fully-human, quadrivalent-hantavirus polyclonal antibody derived from non-human source. |
| title_sort | preclinical evaluation of a fully human quadrivalent hantavirus polyclonal antibody derived from non human source |
| url | http://www.sciencedirect.com/science/article/pii/S120197122400523X |
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