Function matters: Coronavirus cross-binding antibodies do not cross-neutralize.

Background: During the current pandemic, the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) neutralization capacity of the immunoglobulin (IG) supply has changed from undetectable for lots manufactured from plasma collected before the pandemic, to now highly potent.

Objective: As antibodies induced by exposure to or vaccination against coronaviruses were shown to be cross-coronavirus reactive, it was of interest to understand whether SARS-CoV-2 neutralizing antibodies would result in increased functional IG potency also against seasonal coronaviruses.

Methods: IG lots from US plasma collected before SARS-CoV-2 emerged and collected during the pandemic were analyzed by live virus neutralization assay for SARS-CoV-2 and seasonal human coronaviruses (HCoVs) NL63 and OC43 neutralizing antibody content.

Results: Pre-pandemic IG showed no SARS-CoV-2 neutralizing antibody titers. However, IG lots produced from plasma of post-coronavirus disease 2019 (COVID-19) individuals exhibited robust anti-SARS-CoV-2 potency (1,267 IU/ml) which further increased ~4-fold in pandemic IG lots reaching a mean titer of 5,122 IU/ml. Nonetheless, neutralizing antibody potencies to the HCoVs NL63 and OC43 remained stable over this period, i.e., have not increased correspondingly.

Conclusion: The present results show that cross-coronavirus-reactive antibodies are not cross-neutralizing, i.e., SARS-CoV-2 antibodies do not neutralize seasonal coronaviruses NL63 and OC43.