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

Document Type : Original Articles

Authors

1 Department of Virology, School of Public Health, Tehran University of Medical Sciences, Tehran, P.O. Box: 1417613151, Iran; aida.abbasi67@gmail.com; Abbasi-a@student.tums.ac.ir

2 DVM, PhD; Associate Professor- Razi Vaccine and Serum Research Institute (RVSRI) Hessark Karadj Agricultural Research, Education and Extension Organization (AREEO), Tehran, Iran: Tel(+98)2134570038-2253 :Fax (+9821)34572194; Email:

3 Department of Human Viral Vaccines, Razi Vaccine and Serum Research Institute (RVSRI), Agricultural Research, Education, and Extension Organization (AREEO), Karaj, Iran

4 MSc, PhD; Assistant Professor - Razi Vaccine and Serum Research Institute (RVSRI) Hessark Karadj Agricultural Research, Education and Extension Organization (AREEO), Tehran, Iran: Tel(+98)2134570038-2253:Fax (+9821)34572194; Email:

5 Department of Microbiology and Immunology, Faculty of Veterinary Medicine, University of Tehran, Tehran, Iran; naser.sadri@ymail.com; n.sadri@Rvsri.ac.ir; naser.sadri@ut.ac.ir

6 Professor, Head of Department (Virology Department); Department of Virology, School of Public Health, Tehran University of Medical Sciences, Tehran, P.O. Box: 1417613151, Iran; Email: v.salimi@tums.ac.ir; vahidsalimii@gmail.com https://orcid.org/0000

10.32592/ARI.2025.80.1.51

Abstract

Respiratory syncytial virus 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 causes between 100,000 and 200,000 infant deaths annually.
Several vaccine platforms have been introduced for RSV vaccine production. In this study, a local diploid cell line, RAZI-HDC, derived from human fetal lung cells, was used for RSV virus propagation regarding to study live-attenuated vaccine, and was compared to the MRC-5 cell line.
The total cells per 25cm2 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 5 days after starting the culture. The complete cytopathic effect of RSV in RAZI-HDCR-HDC was observed after four days, which indicates 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 showed that both cell substrates have the same function for RSV propagation. Diploid cell lines like MRC-5 and RAZI-HDC are preferred for vaccine manufacturing as they are of human origin and have a stable 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 ability of RAZI-HDC cell line in supporting the RSV replication, were assessed and found to be equivalent to those of MRC-5. 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. Using a locally developed cell line like RAZI-HDC can be somewhat more cost-effective than relying on imported cell substrates.

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References

  1. Shi T, McAllister DA, O'Brien KL, Simoes EA, Madhi SA, Gessner BD, Polack FP, Balsells E, Acacio S, Aguayo C: Global, regional, and national disease burden estimates of acute lower respiratory infections due to respiratory syncytial virus in young children in 2015: a systematic review and modelling study. The Lancet, 2017;390(10098):946-958.
  2. Bont L, Checchia PA, Fauroux B, Figueras-Aloy J, Manzoni P, Paes B, Simões EA, Carbonell-Estrany X: Defining the epidemiology and burden of severe respiratory syncytial virus infection among infants and children in western countries. Infectious Diseases And Therapy, 2016;5:271-298.
  3. Hayat M, Mohd Yusoff MS, Samad MJ, Abdul Razak IS, Md Yasin IS, Thompson KD, Hasni K: Efficacy of feed-based formalin-killed vaccine of Streptococcus iniae stimulates the gut-associated lymphoid tissues and immune response of red hybrid tilapia. Vaccines, 2021;9(1):51.
  4. Nuñez Castrejon AM, O'Rourke SM, Kauvar LM, DuBois RM: Structure-based design and antigenic validation of respiratory syncytial virus G immunogens. Journal of Virology, 2022;96(7):e02201-02221.
  5. Seo SH, Jang Y: Cold-adapted live attenuated SARS-Cov-2 vaccine completely protects human ACE2 transgenic mice from SARS-Cov-2 infection. Vaccines, 2020;8(4):584.
  6. Karron RA, Atwell JE, McFarland EJ, Cunningham CK, Muresan P, Perlowski C, Libous J, Spector SA, Yogev R, Aziz M: Live-attenuated vaccines prevent respiratory syncytial virus–associated illness in young children. American Journal Of Respiratory And Critical Care Medicine, 2021;203(5):594-603.
  7. Jang YH, Seong B-L: Principles underlying rational design of live attenuated influenza vaccines. Clinical And Experimental Vaccine Research, 2012;1(1):35-49.
  8. Herfst S, de Graaf M, Schrauwen EJ, Sprong L, Hussain K, van den Hoogen BG, Osterhaus AD, Fouchier RA: Generation of temperature-sensitive human metapneumovirus strains that provide protective immunity in hamsters. Journal Of General Virology, 2008;89(7):1553-1562.
  9. Mélade J, Piorkowski G, Touret F, Fourié T, Driouich JS, Cochin M, Bouzidi HS, Coutard B, Nougairede A, de Lamballerie X: A simple reverse genetics method to generate recombinant coronaviruses. EMBO Reports, 2022;23(5):e53820.
  10. Durzyńska J, Goździcka-Józefiak A: Viruses and cells intertwined since the dawn of evolution. Virology Journal, 2015;12:1-10.
  11. Jordan I, Sandig V: Matrix and backstage: cellular substrates for viral vaccines. Viruses, 2014; 6:1672–1700.
  12. Kiesslich S, Kamen AA: Vero cell upstream bioprocess development for the production of viral vectors and vaccines. Biotechnology Advances, 2020;44:107608.
  13. Strickler HD, Rosenberg PS, Devesa SS, Hertel J, Fraumeni Jr JF, Goedert JJ: Contamination of poliovirus vaccines with simian virus 40 (1955-1963) and subsequent cancer rates. Jama, 1998;279(4):292-295.
  14. Petricciani J, Sheets R: An overview of animal cell substrates for biological products. Biologicals, 2008;36(6):359-362.
  15. Zhang K, Na T, Wang L, Gao Q, Yin W, Wang J, Yuan B-Z: Human diploid MRC-5 cells exhibit several critical properties of human umbilical cord-derived mesenchymal stem cells. Vaccine, 2014;32(50):6820-6827.
  16. Rodrigues AF, Soares HR, Guerreiro MR, Alves PM, Coroadinha AS: Viral vaccines and their manufacturing cell substrates: New trends and designs in modern vaccinology. Biotechnology Journal, 2015;10(9):1329-1344.
  17. Mahmudi - Gharoeie N, Mohammadi A, Saffar B, Esna -Ashari F, Foroghi A, Alirezaee B, Ghorbani R, Sadigh ZA. Development a New Human Skin Continuous Cell Line Sensitive to Mumps Virus: Iranian Journal of Virology 201 3; 7 (4): 7 - 1 3 ©201 3, Iranian Society of Virology
  18. Mohammad Taqavian, Mohammad Reza Fazeli, Ahmad Fayaz, Nasrin Samadi, Ashraf Mohammadi, Hooshmand Ilka, Najmeh Mahjoubi: A Novel Cell Substrate Candidate for Rabies Virus Vaccine Propagation and Production. International Journal of eISSN: 2470-9980 Vaccines & Vaccination November 19, 2015
  19. Sanjiv R. Shah, Staci R. Kane, Maher Sheikh, and Tensile M. Alfaro: Development of a rapid viability RT-PCR (RV-RT-PCR) method to detect infectious SARS-CoV-2 from swabs. Journal of Virological Methods. 2021 Nov; 297: 114251
Archives of Razi Institute
Volume 80, Issue 1
January and February 2025
Pages 51-59

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