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bioRxiv · 10.1101/2020.06.19.160879

Cross-neutralization activity against SARS-CoV-2 is present in currently available intravenous immunoglobulins

Diez, J. M.·Romero, C.·Vergara Alert, J.·Bello Perez, M.·Rodon, J.·Honrubia, J. M.·Segales, J.·Sola, I.·Enjuanes, L.·Gajardo, R.
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Abstract

BackgroundThere is a crucial need for effective therapies that are immediately available to counteract COVID-19 disease. Recently, ELISA binding cross-reactivity against components of human epidemic coronaviruses with currently available intravenous immunoglobulins (IVIG) Gamunex-C and Flebogamma DIF (5% and 10%) have been reported. In this study, the same products were tested for neutralization activity against SARS-CoV-2, SARS-CoV and MERS-CoV and their potential as an antiviral therapy. MethodsThe neutralization capacity of six selected lots of IVIG was assessed against SARS-CoV-2 (two different isolates), SARS-CoV and MERS-CoV in cell cultures. Infectivity neutralization was measured by determining the percent reduction in plaque-forming units (PFU) and by cytopathic effects for two IVIG lots in one of the SARS-CoV-2 isolates. Neutralization was quantified using the plaque reduction neutralization test 50 (PRNT50) in the PFU assay and the half maximal inhibitory concentration (IC50) in the cytopathic/cytotoxic method (calculated as the minus log10 dilution which reduced the viral titer by 50%). ResultsAll IVIG preparations showed neutralization of both SARS-CoV-2 isolates, ranging from 79 to 89.5% with PRNT50 titers from 4.5 to >5 for the PFU method and ranging from 47.0%-64.7% with an IC50 ~1 for the cytopathic method. All IVIG lots produced neutralization of SARS-CoV ranging from 39.5 to 55.1 % and PRNT50 values ranging from 2.0 to 3.3. No IVIG preparation showed significant neutralizing activity against MERS-CoV. ConclusionIn cell culture neutralization assays, the tested IVIG products contain antibodies with significant cross-neutralization capacity against SARS-CoV-2 and SARS-CoV. However, no neutralization capacity was demonstrated against MERS-CoV. These preparations are currently available and may be immediately useful for COVID-19 management.

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Diez, J. M., Romero, C., Vergara Alert, J., Bello Perez, M., Rodon, J., Honrubia, J. M., Segales, J., Sola, I., Enjuanes, L., Gajardo, R.. 2020-06-19. Cross-neutralization activity against SARS-CoV-2 is present in currently available intravenous immunoglobulins. https://doi.org/10.1101/2020.06.19.160879

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