Assessment of the immunogenicity of residual host cell protein impurities of OsrHSA.

Naghmeh Abiri,Bo Shi,Jianlei Pang,Xianghong Wang,Sucai Zhang,Yunxia Sun,Jiquan Ou,Daichang Yang,Zonghua Wang

doi:10.1371/journal.pone.0193339

Abstract

Human serum albumin (HSA) is the most abundant protein in human plasma and is widely used at high doses for treating various diseases. Recombinant HSA is an alternative approach to plasma-derived HSA, providing increased safety and an unlimited supply. However, the safety of the residual host cell proteins (HCPs) co-purified with Oryza sativa HSA (OsrHSA) remains to be determined. An animal system was used to assess the immunogenicity of OsrHSA and its residual HCPs. Low immunogenicity and immunotoxicity of the residual HCPs at a dose of 25 μg/kg, equivalent to 25 times the clinical dosage of HSA, were observed. An anti-drug-antibody (ADA) analysis revealed that anti-HSA, anti-OsrHSA or anti-HCP antibodies developed with a low frequency in pHSA and OsrHSA treatments, but the titers were as low as 1.0–2.0. Furthermore, the titer and the incidence of the specific antibodies were not significantly different between the pHSA and OsrHSA groups, indicating that OsrHSA presents similar immunogenicity to that of pHSA. More importantly, no cytokines were stimulated after the administration of OsrHSA and the residual HCPs, suggesting that there was no risk of a cytokine storm. These results demonstrated that the residual HCPs from OsrHSA have low immunogenicity, indicating that the rice endosperm is one of the best hosts for plant molecular pharming.

Highlights

Molecular pharming refers to the use of a host, either plant or animal, for the large-scale production of commercially valuable recombinant proteins
A significant difference was observed in female animals in the plasma-derived HSA (pHSA) group at Day 15 compared with that in the negative control group (P
Because OsrHSA is biochemically and physically identical to pHSA [5], the safety concern of OsrHSA does not come from Human serum albumin (HSA) itself but from the residual host cell proteins (HCPs) and other impurities produced during OsrHSA processing

Summary

Introduction

Molecular pharming refers to the use of a host, either plant or animal, for the large-scale production of commercially valuable recombinant proteins. Vaccines, antibodies and other pharmaceuticals, totaling more than 108 pharmaceutical proteins, have been produced via plant molecular pharming [1,2,3,4,5,6,7,8,9,10,11,12,13,14,15]. Two plant-made pharmaceuticals (PMPs), SIgA, called CaroRx, and the glucocerebrosidase Elelyso, have been approved by regulatory authorities [17,18]. One reason for the lack of regulatory approval is concern regarding the level and population of residual host cell proteins (HCPs) in PMPs, which could produce potential immunogenicity [19].

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Conclusion