Hyperimmune serum consisting of purified antibody fragments produced in horses may be an efficient approach to combat Covid-19, researchers report.
Tests in hamsters improved the animals’ clinical conditions, the scientists said.
The neutralizing activity of the sera proved to be high against two variants, they reported in the journal iScience.
The research opens up the possibility of developing a passive immunization or treatment against SARS-CoV-2 infection.
“By using the trimeric spike protein of SARS-CoV-2 to immunize horses, a cocktail of purified immunoglobulin G fragments (F(ab’)2) showing very high neutralizing activity was developed,” said Professor Leda Castilho, who co-ordinates the laboratory at the Federal University of Rio de Janeiro that produces the recombinant spike protein used for horse hyperimmunization.
“This,” she continued, “might be a useful countermeasure against Covid-19, with the added advantages of being an affordable alternative that can be produced in horse serum production facilities available worldwide.”
The scientists are confident of the efficiency of the new product.
Study co-ordinator Professor Jerson Silva, also with the Federal University of Rio de Janeiro, said: “The main finding in our study is that the equine hyperimmune globulins antibodies developed against the spike protein of the ancestral SARS-CoV-2 had high neutralizing action against the new variants of the virus, such as the gamma strain.
“The polyclonal nature explains this high potency, which can be tailored now by using a combination of mutant spike protein from different variants as antigens.”
Equine immunization is a well-known and easily scalable technology proven to generate high titers of neutralizing antibodies, and has been used to treat many diseases, such as rabies, tetanus, as well as bites from poisonous snakes.
Since equine antivenom products are routinely produced in both high and low-income countries, the Brazilian strategy could be easily reproduced in any part of the world and could be rapidly tested as a therapy or passive immunization tool for covid-19.
Previous work on equine hyperimmune sera against SARS-CoV and MERS-CoV had shown positive results for these closely related betacoronaviruses. Another recent study has shown that the recombinant receptor-binding domain (RBD) of the SARS-CoV-2 S protein could stimulate antibody production in mice and equines.
In the Brazilian study, the scientists used the recombinant trimeric spike (S) glycoprotein to immunize horses for the production of hyperimmune globulins against SARS-CoV-2. The technique combines the advantages of using an antigen that closely resembles its state on the surface of the native virus with the biosafety advantages related to using a recombinant immunogen.
After developing the horse hyperimmune F(ab’)2 concentrate, the group carried out challenge tests in hamsters. The researchers evaluated the pretreatment and treatment after SARS-CoV-2 infection.
The results showed the ability of the treatment to reduce viral load in pulmonary tissues, and to improve the animals’ clinical conditions, as reflected by weight gain. All intervention schemes protected the animals against weight loss in the acute phase of the disease. Non-treated animals showed an increased weight loss, whereas pre-treatment resulted in no body-weight reduction.
The next step of the research is to conduct a phase 1/2 clinical trial in humans. The trial protocol has already been approved by the Brazilian national ethics committee.
The clinical trial will investigate all safety aspects, as well as the duration of hospitalization, viral load, and progression to assisted ventilation.
The research consortium is formed by researchers from the Federal University of Rio de Janeiro, the Vital Brazil Institute, and the Oswaldo Cruz Foundation.
The study was funded by the National Council for Scientific and Technological Development (CNPq), the Brazilian Ministry of Science, Technology, and Innovation for Virus Network, the Carlos Chagas Filho Foundation for Research Support in the State of Rio de Janeiro (FAPERJ), the Coordination of Improvement of Higher Education (CAPES/MEC) and the National Institute of Science and Technology for Structural Biology and Bioimaging (INBEB).
Cunha, L.E.R., Stolet, A.A., Strauch, M.A., Pereira, V.A.R., Dumard, C.H., Gomes, A.M.O., Monteiro, F.L., Higa, L.M., Souza, P.N.C., Fonseca, J.G., Pontes, F.E., Meirelles,
L.G.R., Albuquerque, J.W.M., Sacramento, C.Q., Fintelman-Rodrigues, N., Lima, T.M., Alvim, R.G.F., Marsili, F.F., Caldeira, M.M., Zingali, R.B., de Oliveira, G.A.P., Souza, T.M.L., Silva, A.S., Muller, R., Rodrigues, D.d.R.F., Jesus da Costa, L., Alves, A.D.R., Pinto, M.A., Oliveira, A.C., Guedes, H.L.M., Tanuri, A., Castilho, L.R., Silva, J.L., Polyclonal F(ab’)2 fragments of equine antibodies raised against the spike protein neutralize SARS-CoV-2 variants with high potency, ISCIENCE (2021), doi: https://doi.org/10.1016/j.isci.2021.103315.