Human Polyclonal Antibodies Produced from Transchromosomal Bovine Provides Prophylactic and Therapeutic Protections Against Zika Virus Infection in STAT2 KO Syrian Hamsters
Abstract
:1. Introduction
2. Materials and Methods
2.1. Virus
2.2. Production of Anti-ZIKV Human Polyclonal Antibodies SAB-155 from Transchromosomal Bovine
2.3. STAT2 KO Golden Syrian Hamsters
2.4. Serum and Tissue Collection
2.5. ZIKV Plaque Reduction Neutralization Test (PRNT)
2.6. ZIKV RT-PCR
2.7. Immunohistochemistry (IHC) and Histology
2.8. Ethics Statement
3. Results
3.1. ZIKV Infection in STAT2 KO Hamsters
3.2. Prophylactic Treatment by SAB-155 of ZIKV Infection in STAT2 KO Hamsters
3.3. Therapeutic Treatment by SAB-155 of ZIKV Infection in STAT2 KO Hamsters and Identifying the Effective Treatment Time Windows
3.4. Dose Titration of Therapeutic Treatment with SAB-155 against ZIKV Infection
4. Discussion
Author Contributions
Funding
Acknowledgments
Conflicts of Interest
References
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Treatment Day | SAB-155 Antibody Dosage | Testis | |||||
---|---|---|---|---|---|---|---|
ZIKV RNA by RT-PCR | Morphological Diagnoses * | Immunohistochemistry | Lesions/Total No. of Male Hamster Necropsied | ||||
Identifying effective day of antibody treatment ** | SAB -155 treatment | −1 dpi | 100 mg/kg | Below the limit of detection (<105.5) | No significant lesions | 4/4 No ZIKV infected cells found | 0/4 |
3 dpi | 100 mg/kg | Below the limit of detection (<105.5) | No significant lesions | 4/4 No ZIKV infected cells found | 0/4 | ||
4.5 dpi | 100 mg/kg | 106–1010 | Pyogranulomatous inflammatory exudate infiltrates. | 1/4 animal had ZIKV antigen in ST. | 1/4 | ||
Negativecontrols | 1 dpi | Irrelevant Ab. 100 mg/kg | 109 | Diffusely pyogranulomatous inflammatory exudate infiltrates expand and replaces the interstitium of ST. | 2/4 animal had ZIKV antigen in ST. 2/4 animal died before 21 dpi. | 2/2 | |
Uninfected controls ** | 1 dpi | 100 mg/kg | Below the limit of detection (<105.5) | No significant lesions | No ZIKV infected cells found | 0/4 | |
1 dpi | Irrelevant Ab. 100 mg/kg | Below the limit of detection (<105.5) | No significant lesions | No ZIKV infected cells found | 0/4 | ||
Identifying effective dose of antibody treatment *** | SAB-155treatment | 4.5 dpi | 200 mg/kg | 106–1011 | 1/6 with a minimal pyogranulomatous orchitis.4/6 with a severe pyogranulomatous orchitis | 6/6 animals had ZIKV antigen in ST. | 6/6 |
4.5 dpi | 400 mg/kg | 105–108 | 1/6 with a severe pyogranulomatous orchitis. | 6/6 animals had ZIKV antigen in ST. | 6/6 | ||
Negative controls | 4.5 dpi | Irrelevant Ab. 400 mg/kg | 106–1010 | 5/6 with a severe pyogranulomatous orchitis. | 5/6 animals had ZIKV antigen in ST.1/6 animal had coagulative necrotic testis. 1/6 animal died before 21 dpi. | 5/6 | |
1 dpi | Irrelevant Ab. 100 mg/kg | 108 | 3/4 animal died before necropsy. One animal survived with severe pyogranulomatous orchitis. | 3/4 animal died before necropsy.1/4 animal with heavy ZIKV+ve ST. | 1/1 | ||
UninfectedControls *** | 1 dpi | 100 mg/kg | Below the limit of detection (<105.5) | No significant lesions | No ZIKV infected cells found | 0/6 | |
1 dpi | Irrelevant Ab. 400 mg/kg | Below the limit of detection (<105.5) | No significant lesions | No ZIKV infected cells found | 0/6 | ||
1 dpi | Vehicle | Below the limit of detection (<105.5) | No significant lesions | No ZIKV infected cells found | 0/6 |
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Siddharthan, V.; Miao, J.; Van Wettere, A.J.; Li, R.; Wu, H.; Sullivan, E.; Jiao, J.; Hooper, J.W.; Safronetz, D.; Morrey, J.D.; et al. Human Polyclonal Antibodies Produced from Transchromosomal Bovine Provides Prophylactic and Therapeutic Protections Against Zika Virus Infection in STAT2 KO Syrian Hamsters. Viruses 2019, 11, 92. https://doi.org/10.3390/v11020092
Siddharthan V, Miao J, Van Wettere AJ, Li R, Wu H, Sullivan E, Jiao J, Hooper JW, Safronetz D, Morrey JD, et al. Human Polyclonal Antibodies Produced from Transchromosomal Bovine Provides Prophylactic and Therapeutic Protections Against Zika Virus Infection in STAT2 KO Syrian Hamsters. Viruses. 2019; 11(2):92. https://doi.org/10.3390/v11020092
Chicago/Turabian StyleSiddharthan, Venkatraman, Jinxin Miao, Arnaud J Van Wettere, Rong Li, Hua Wu, Eddie Sullivan, Jinan Jiao, Jay W. Hooper, David Safronetz, John D. Morrey, and et al. 2019. "Human Polyclonal Antibodies Produced from Transchromosomal Bovine Provides Prophylactic and Therapeutic Protections Against Zika Virus Infection in STAT2 KO Syrian Hamsters" Viruses 11, no. 2: 92. https://doi.org/10.3390/v11020092
APA StyleSiddharthan, V., Miao, J., Van Wettere, A. J., Li, R., Wu, H., Sullivan, E., Jiao, J., Hooper, J. W., Safronetz, D., Morrey, J. D., Julander, J. G., & Wang, Z. (2019). Human Polyclonal Antibodies Produced from Transchromosomal Bovine Provides Prophylactic and Therapeutic Protections Against Zika Virus Infection in STAT2 KO Syrian Hamsters. Viruses, 11(2), 92. https://doi.org/10.3390/v11020092