Preservation of neutralizing antibody function in COVID‐19 convalescent plasma treated using a riboflavin and ultraviolet light‐based pathogen reduction technology

Abstract

Background and objectives Convalescent plasma (CP) has been embraced as a safe therapeutic option for coronavirus disease 2019 (COVID-19), while other treatments are developed. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is not transmissible by transfusion, but bloodborne pathogens remain a risk in regions with high endemic prevalence of disease. Pathogen reduction can mitigate this risk; thus, the objective of this study was to evaluate the effect of riboflavin and ultraviolet light (R + UV) pathogen reduction technology on the functional properties of COVID-19 CP (CCP). Materials and methods COVID-19 convalescent plasma units (n = 6) from recovered COVID-19 research donors were treated with R + UV. Pre-and post-treatment samples were tested for coagulation factor and immunoglobulin retention. Antibody binding to spike protein receptor-binding domain (RBD), S1 and S2 epitopes of SARS-CoV-2 was assessed by ELISA. Neutralizing antibody (nAb) function was assessed by pseudovirus reporter viral particle neutralization (RVPN) assay and plaque reduction neutralization test (PRNT).Results Mean retention of coagulation factors was ≥70%, while retention of immunoglobulins was 100%. Starting nAb titres were low, but PRNT 50 titres did not differ between pre-and post-treatment samples. No statistically significant differences were detected in levels of IgG (P ≥ 0Á3665) and IgM (P ≥ 0Á1208) antibodies to RBD, S1 and S2 proteins before and after treatment.Conclusion R + UV PRT effects on coagulation factors were similar to previous reports, but no significant effects were observed on immunoglobulin concentration and antibody function. SARS-CoV-2 nAb function in CCP is conserved following R + UV PRT treatment.

Review of therapeutic mechanisms and applications based on SARS-CoV-2 neutralizing antibodies

“…The 1918 influenza pandemic demonstrated the effectiveness use of CP. This therapy has been successfully used to treat emerging infectious diseases (EID) such as severe acute respiratory syndrome (SARS), Middle East respiratory syndrome (MERS), and Ebola virus disease ( Yonemura et al, 2021 ).…”

“…Riboflavin and ultraviolet pathogen reduction (R + UV PRT) have been shown in studies to reduce the risk of pathogen transmission during blood transfusions while also having therapeutic effects on blood coagulation factors. More critically, R + UV PRT had a little effect on immunoglobulin concentration (including the IgG subclass), preserving the neutralizing ability of CP (Yonemura et al, 2021). By undergoing immunoadsorption, several researchers have developed that collect concentrated immunoglobulins rather than whole plasma units.…”

SARS‐CoV‐2 neutralising antibody therapies: Recent advances and future challenges

“…Its effectiveness was first demonstrated during the 1918 influenza pandemic and has since been successfully employed in combating emergent infectious diseases, including SARS, MERS, and the formidable Ebola virus disease. [71][72][73] The administration of CP can inhibit viral replication via COVID-19-neutralising antibodies and modulate the inflammatory response through additional immunomodulatory mechanisms, such as the complement system, antibody-dependent cellular toxicity, and phagocytosis. 8 CoV-2 antibodies upon their initial presentation.…”

“…Convalescent plasma (CP), enriched with neutralising antibodies from individuals who have recovered from illness, serves as a valuable source for passive immunotherapy in both infected and susceptible populations. Its effectiveness was first demonstrated during the 1918 influenza pandemic and has since been successfully employed in combating emergent infectious diseases, including SARS, MERS, and the formidable Ebola virus disease 71–73 …”

“…Studies have demonstrated that innovative combination of riboflavin and ultraviolet pathogen reduction (R + UV PRT) serves to diminish the risk of pathogen transmission during blood transfusions, while simultaneously exerting beneficial effects on blood coagulation factors. Crucially, R + UV PRT exerts a minimal impact on immunoglobulin concentrations, encompassing the IgG subclass, thereby preserving the neutralising potential of convalescent plasma for therapeutic applications 71 . Some researchers have embraced the technique of immunoadsorption to procure concentrated immunoglobulins, as opposed to relying solely on the collection of whole plasma units, thereby enhancing the specificity and effectiveness of the therapeutic approach.…”