Polyclonal F(ab’)
2 Fragments of Equine Antibodies Raised Against Recombinant SARS-CoV-2 Spike Protein Neutralize the P.1 and P.2 Strains with High Potency
Universidade Federal do Rio de Janeiro (UFRJ) - Departamento de Genética; Universidade Federal do Rio de Janeiro (UFRJ) - Laboratório de Virologia Molecular
We used the trimeric spike (S) glycoprotein (residues 1-1208) in the prefusion conformation to immunize horses for the production of hyperimmune globulins against SARS-CoV-2. Serum antibody titers measured by anti-spike ELISA were above 1:106, and neutralizing antibody titer against an early isolate of authentic virus (WT) was 1:14,604 (average PRNT90), which is 140-fold higher than the average neutralizing titer of plasma from three convalescent COVID-19 patients analyzed for comparison. Using the same technology routinely used for industrial production of other horse hyperimmune products, plasma from immunized animals was pepsin digested to remove the Fc portion and purified, yielding an F(ab’)2 preparation with PRNT90 titers 150-fold higher than the neutralizing titers in human convalescent plasma. Repeating the hyperimmunization in a second group of horses confirmed the very high neutralizing titers in serum and in a GMP clinical F(ab’)2 lot. Virus-neutralizing activity in samples from mice that received the F(ab’)22 was similar against WT and P.2 but displaced to higher concentrations by 0.39 log units against P.1. The neutralizing activity against P.1 can be explained by the polyclonal nature of the raised antibody against the whole spike protein. These results support the possibility of using equine F(ab’)2 preparation for the clinical treatment of COVID patients.
Cunha, Luis Eduardo R. and Stolet, Adilson A. and Strauch, Marcelo A. and Pereira, Victor A. R. and Dumard, Carlos H. and Gomes, Andre M. O. and Monteiro, Fabio L. and Higa, Luiza M. and Souza, Patrícia N. C. and Fonseca, Juliana G. and Pontes, Francisco E. and Meirelles, Leonardo G. R. and Albuquerque, José W. M. and Sacramento, Carolina and Fintelman-Rodrigues, Natalia and Lima, Tulio M. and Alvim, Renata G. F. and Marsili, Federico F. and Caldeira, Marcella M. and Zingali, Russolina B. and de Oliveira, Guilherme A. P. and Souza, Thiago and Oliveira, Andrea C. and Guedes, Herbert L. M. and Tanuri, Amilcar and Castilho, Leda R. and Silva, Jerson and Administrator, Sneak Peek, Polyclonal F(ab’)
2 Fragments of Equine Antibodies Raised Against Recombinant SARS-CoV-2 Spike Protein Neutralize the P.1 and P.2 Strains with High Potency. Available at SSRN: https://ssrn.com/abstract=3846539 or http://dx.doi.org/10.2139/ssrn.3846539
This version of the paper has not been formally peer reviewed.
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