Propagation Properties of a New Human Diploid Cell Line, RAZI-HDC, and Its Suitability as a Candidate Cell Substrate for Respiratory Syncytial Virus Vaccine Production in Comparison to MRC-5.

Abstract

Respiratory syncytial virus (RSV) is a common cause of infection of the respiratory tract in infants, older adults, individuals with heart and lung disease, and immunocompromised patients. The disease is responsible for between 100,000 and 200,000 infant deaths on an annual basis. RSV vaccine production platforms have been developed. In this study, a local diploid cell line, RAZI-HDC, derived from human fetal lung cells, was utilized for RSV virus propagation with the objective of studying live-attenuated vaccine, and was compared to the MRC-5 cell line. The total cells per 25-cm² flask were 44.0 ± 2.6 *105 and 41.66 ± 2.08 *105 for MRC-5 and RAZI-HDC, respectively. The maximum cell-specific growth rate of RAZI-HDC was 316.66 ± 20.81, while that of MRC-5 was only 340 ± 26.45. The maximum cell division number of RAZI-HDC was 1.24 ± 0.07, in comparison to the MRC-5, with a maximum cell division number of 1.32 ± 0.08. Both cell substrates achieved maximum cell density five days after the initiation of the culture. The complete cytopathic effect of RSV in RAZI-HDC-RAZI-HDC was observed after four days, indicating the sensitivity of these cells to RSV. The virus productivity in RAZI-HDC cells (2.4685) was not significantly different from that in MRC-5 cells (2.5), as determined by a two-tailed t-test (p=0.78). The results indicated that both cell substrates function similarly in terms of RSV propagation. It is noteworthy that diploid cell lines, such as MRC-5 and RAZI-HDC, are particularly well-suited for vaccine manufacturing. This is primarily due to their human origin and the stability of their karyotype. This is a significant advantage, as it helps ensure the safety of the final vaccine product if these cells are used to make viral vaccines that require virus amplification. The study further assessed the replication capacity of the RAZI-HDC cell line and found it to be equivalent to that of the MRC-5 cell line. Specifically, the maximum virus productivity in RAZI-HDC cells (2.4685 log TCID50/mL) was not significantly different from that in MRC-5 cells (2.5 log TCID50/mL), as determined by statistical analysis. The utilization of a locally developed cell line such as RAZI-HDC has the potential to be more cost-effective in comparison to relying on imported cell substrates.