History repeats itself: horse originated hyperimmune sera production against SARS CoV-2.
Abstract: SARS-CoV-2 disease was announced as a pandemic by The World Health Organization in early 2020. It is still threatening the world population. Here, we aimed to produce hyperimmune sera that contain immunoglobulin G and F(ab')2 fragments sourced from horse antibodies as an urgent response to the pandemic. SARS-CoV-2 was produced and inactivated with three different methods [formaldehyde (FA), formaldehyde, and binary ethylene amine (FA + BEI), and heat treatment]. After in vitro inactivation control, immunogens were mixed with Freund’s adjuvant, thereafter horses (n: 2 for FA, 4 for FA + BEI, 2 for heat inactivation) and New Zealand rabbits (n: 6 for FA, 6 fo r FA + BEI, 6 for heat inactivation) were immunized four times. Neutralizing antibody levels of the sera were measured at the 4th, 6th, and 8th weeks. When the antibodies were detected at the peak level, plasma was collected from horses and hyperimmune sera procured after the purification process. Horses and rabbits produced highly neutralizing antibodies against the SARS-CoV-2 in FA and FA + BEI inactivation groups, foreign proteins were removed effectively after purification. This study presents a profitable practice to develop specific antisera in horses against SARS-CoV-2 for emergency and low-cost response. In further studies, new purification methods can be used to increase the efficiency of the final product.
This work is licensed under a Creative Commons Attribution 4.0 International License.
Publication Date: 2021-10-21 PubMed ID: 34092050DOI: 10.3906/sag-2101-304Google Scholar: Lookup
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Summary
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The research is aimed at developing a low-cost and quick response treatment for SARS-CoV-2, by creating hyperimmune sera from horse antibodies that have been exposed to the virus.
Objective of the Study
The study is an attempt to address the SARS-CoV-2 pandemic with an unconventional yet historical response – creating a treatment using hyperimmune sera extracted from horse antibodies. The goal is to generate an efficient, economical, and emergency response system.
Methodology
- The researchers first cultured and then inactivated the SARS-CoV-2 virus using three distinct methods – formaldehyde (FA), a combination of formaldehyde and binary ethylene amine (FA + BEI), and through heat treatment.
- After ensuring successful inactivation, these immunogens were mixed with a substance known as Freund’s adjuvant to enhance the immune response.
- Several horses and New Zealand rabbits were then immunized four times with these mixtures. The exact numbers varying for each type of inactivation method. The study documented that two horses were used for FA method, four for the FA + BEI method, and another two for the heat treatment method. The same trend followed with the rabbits with six being used for each method.
- Over a span of 8 weeks, the researchers measured the neutralizing antibody levels in the sera at the 4th week, 6th week, and 8th week.
- Once the antibodies had reached peak levels, plasma was extracted from the horses and a hyperimmune serum was collected after undergoing a purification process.
Findings
- The horses and rabbits produced highly neutralizing antibodies against SARS-CoV-2 specifically in the FA and FA + BEI inactivation groups. These neutralizing antibodies can potentially stop the virus from entering the cells and causing infection.
- It was observed that foreign proteins present were effectively removed after conducting the purification process, which indicates a successful extraction of hyperimmune sera.
Implications and Future Work
- The researchers posit this study as a feasible technique to create specific antisera against SARS-CoV-2 in horses, providing a low-cost and ready response solution.
- From the study’s success, it is suggested that future work can look into optimizing the purification methods to improve the efficiency of the resulting product. This can lead to a hyperimmune serum with even better neutralization capabilities against the virus.
This research demonstrates an innovative use of a time-tested technique in response to a modern-day health crisis.
Cite This Article
APA
Pakdemirli A, Çalışkan E, Hacıoğlu S, Danyer E, Kardoğan Ö, Kurt ZE, Yıldırım Ö, Taşkaya H, Ündar B, Sezgin Y, Ergin G, Ekici H, Ülker U, Taçbaş E, Çakır Ş, Bülbül R, Bebek M, Sarper M, Dülger D, Sarı ÜS, Ergin F, Kabaklı Ö, Yaralı C.
(2021).
History repeats itself: horse originated hyperimmune sera production against SARS CoV-2.
Turk J Med Sci, 51(5), 2263-2273.
https://doi.org/10.3906/sag-2101-304 Publication
Researcher Affiliations
- Department of Physiology, Gülhane School of Medicine, University of Health Sciences, Ankara, Turkey.
- Veterinary Control Central Research Institute, Ankara, Turkey.
- Veterinary Control Central Research Institute, Ankara, Turkey.
- Veterinary Control Central Research Institute, Ankara, Turkey.
- Veterinary Control Central Research Institute, Ankara, Turkey.
- Veterinary Control Central Research Institute, Ankara, Turkey.
- Veterinary Control Central Research Institute, Ankara, Turkey.
- Veterinary Control Central Research Institute, Ankara, Turkey.
- Veterinary Control Central Research Institute, Ankara, Turkey.
- Veterinary Control Central Research Institute, Ankara, Turkey.
- General Directorate of Food and Control, Ankara, Turkey.
- Foot and Mouth Disease Institute, Ankara, Turkey.
- Veterinary Control Central Research Institute, Ankara, Turkey.
- General Directorate of Agricultural Research and Policies, Ankara, Turkey.
- General Directorate of Agricultural Research and Policies, Ankara, Turkey.
- General Directorate of Agricultural Research and Policies, Ankara, Turkey.
- General Directorate of Food and Control, Ankara, Turkey.
- Gülhane Health Sciences Institute, Stem Cell Laboratory, University of Health Sciences, Ankara, Turkey.
- Department of Microbiology, Faculty of Medicine, University of Karabük, Karabük, Turkey.
- Ankara 29 Mayıs State Hospital, Ankara, Turkey.
- VETAL, Adıyaman, Turkey.
- Veterinary Control Central Research Institute, Ankara, Turkey.
- Veterinary Control Central Research Institute, Ankara, Turkey.
MeSH Terms
- Animals
- Horses
- Immune Sera / pharmacology
- Immunologic Factors / pharmacology
- Rabbits
- SARS-CoV-2 / drug effects
- COVID-19 Drug Treatment
Conflict of Interest Statement
The authors have no conflict of interest.
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