Abstract
MRC-5 represents the most frequent human diploid cells (HDCs)-type cell substrate in the production of human viral vaccines. However, early-passage MRC-5 is diminishing and, due to both technical and ethical issues, it is extremely difficult to derive novel HDCs from fetal lung tissues, which are the common sources of HDCs. Our previous studies suggested that human umbilical cord may represent an alternative but convenient source of new HDCs. Here, we established a three-tiered cell banking system of a hUC-MSC line, designated previously as Cell Collection and Research Center-1 (CCRC-1). The full characterization indicated that the banked CCRC-1 cells were free from adventitious agents and remained non-tumorigenic. The CCRC-1 cells sustained its rapid proliferation even at passage 30 and were susceptible to the infection of a wide spectrum of viruses. Interestingly, the CCRC-1 cells showed much higher production of EV71 or Rubella viruses than MRC-5 and Vero cells when growing in serum-free medium. More importantly, the EV71 vaccine produced from CCRC-1 cells induced immunogenicity while eliciting no detectable toxicities in the tested mice. Collectively, these studies further supported that CCRC-1, and likely other hUC-MSCs as well, may serve as novel, safe and high-yielding HDCs for the production of human viral vaccines.
Highlights
Cell substrates have been commonly utilized as the most critical starting materials in manufacturing biological products, including both recombinant proteins and vaccines[1,2]
It was found that the (Cell Collection and Research Center-1) cells, an hUC-Mesenchymal stem cells (MSCs) cell line reported in the previous studies, sustained primitive characteristics during extensive expansion and exhibited a similar sensitivity to the infection of EV71 and Rubella viruses as MRC-5, suggesting that hUC-MSCs may meet the same requirements as the traditional human diploid cell lines (HDCs) for the production of human vaccines[17]
To further validate that hUC-MSCs can potentially serve as a novel group of HDCs, and to establish Collection and Research Center-1 (CCRC-1) as a novel HDC cell substrate for vaccine production, the CCRC-1 cells cultured in α-MEM complete medium was continuously expanded by observing an industry cell banking standard to generate a three-tiered cell banking system, in which the primary cell bank (PCB) was at passage 9, the master cell bank (MCB) at passage 13, and the working cell bank (WCB) at passage 171–4
Summary
Cell substrates have been commonly utilized as the most critical starting materials in manufacturing biological products, including both recombinant proteins and vaccines[1,2]. HDCs, such as WI-38 and MRC-5, derived from human fetal lungs, maintain normal karyotype as well as non-tumourigenic characteristics during a finite serial propagation They have been used in the manufacture of human vaccines for many years without causing serious vaccine-associated adverse events and are considered as the safest cell substrates for the production of human viral vaccines[10,11]. Our recent studies demonstrated that many HDCs established from fetal lungs, such as MRC-5, exhibited several critical properties of human umbilical cord-derived mesenchymal stem cells (hUC-MSCs), including cell morphology, growth activity, expression of cell surface markers, abilities to differentiate into multiple cell lineages and immunomodulatory activities[17]. It was found that the (Cell Collection and Research Center-1) cells, an hUC-MSC cell line reported in the previous studies, sustained primitive characteristics during extensive expansion and exhibited a similar sensitivity to the infection of EV71 and Rubella viruses as MRC-5, suggesting that hUC-MSCs may meet the same requirements as the traditional HDCs for the production of human vaccines[17]
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