Cell-based vaccines are developed from mammalian or more rarely avian or insect cell lines rather than the more common method which uses the cells in embryonic chicken eggs to develop the antigens.[1] The potential use of cell culture techniques in developing viral vaccines has been widely investigated in the 2000s as a complementary and alternative platform to the current egg-based strategies.[1][2]

Vaccines work to prepare an immune system to fight off disease by generating an immune response to disease-causing agents. This immune response enables the immune system to act more quickly and effectively when exposed to that antigen again,[3] and is the most effective tool to date to prevent the spread of infectious diseases.[4]

Production

To produce viral vaccines, candidate vaccine viruses are grown in mammalian, avian or insect tissue culture of cells with a finite lifespan.[5] These cells are typically Madin-Darby Canine Kidney cells,[6] but others are also used including monkey cell lines pMK and Vero and human cell lines HEK 293, MRC 5, Per.C6, PMK, and WI-38.[7] The candidate vaccine virus strain will replicate using the mammalian cells. Next, the virus is extracted from the cells in the liquid culture, purified, then tested or modified for the specific vaccine being produced.[6]

Advantages

The main benefit of cell-based vaccines is the ability to rapidly produce vaccine supplies during an impending pandemic. Cell-based antigen production offer a faster and more stable production of vaccines compared to embryonic chicken eggs, which produce 1-2 vaccine doses per chicken egg.[8] Though host cells replicate well in chicken eggs, vaccine production with mammalian cells would not rely on an adequate supply of chicken eggs to produce each vaccine.[1] In addition, cell-based vaccines may allow for multiple viral vaccines be produced in the same production platforms and facilities in a more sterile environment.[1][7] In addition, some strains do not grow well on embryonic chicken eggs.[1]

Cell lines grown in synthetic media avoid animal serum, which may pose a sterility problem, more specifically, preventing the spread of transmissible spongiform encephalopathies.[9][10][11] Another benefit is the avoidance of egg-allergen. Lastly, cell-based vaccines may be more effective given that, with egg-based vaccines, there is a risk that the virus may mutate (antigenic drift) during its long growth phase in the chicken egg, thus causing the immune system to produce a different antibody than originally intended.[12]

Approved examples

Influenza

Flublok

In 2013, FluBlok, which is produced with insect cells, was approved by the United States Food and Drug Administration, for use in the United States. Developed by Protein Sciences Corporation, it is suitable for people with egg allergies.[13][14][15][16][17]

Flucelvax

In 2012, the US FDA approved Flucelvax as the first mammalian cell-based Influenza vaccine in the United States.[18][19][13] The vaccine was produced by Novartis through culturing of the Madin-Darby canine kidney cell line.[12][20][21] Specifically, Flucelvax targets four Influenza sub-types which includes Influenza A subtype H1N1, Influenza A subtype H3N2, and two Influenza B viruses.[22] The vaccine is approved for people over the age of three years.[22] As of 2013, Flucelvax had shown similar levels of vaccine efficacy and immunogenicity as traditional egg-based vaccines.[23]

Optaflu

Optaflu, produced by Novartis, was approved by the European Medicines Agency in 2009, for use in countries affiliated with the European Union.[24] Optaflu is nearly identical to Flucelvax; it is also produced in Madin-Darby canine kidney cells and targets the same Influenza subtypes.[24] The main differences are in release specifications for measuring vaccine lots' safety, efficacy, and quality, mostly due to differences between U.S. and European regulatory standards and tests.[25]

Rotavirus

The Food and Drug Administration approved two mammalian vero cell based vaccines for rotavirus, Rotarix by GlaxoSmithKline and RotaTeq by Merck.[26]

Measles

Attenuvax is a vaccine approved in 2007, against measles developed using a primary cell line.[8]

Smallpox

ACAM2000 is a smallpox vaccine approved by the Food and Drug Administration in 2007.[26]

Polio

IPOL, developed by Sanofi Pasteur, was approved by the Food and Drug Administration in 1987.[26]

Rabies

Verorab, developed by Sanofi Pasteur, is a mammalian vero cell based rabies vaccine approved by the World Health Organization.[27]

Others

Ixiaro by Valneva SE for Japanese encephalitis.[28]

References

  1. 1 2 3 4 5 Audsley JM, Tannock GA (1 August 2008). "Cell-based influenza vaccines: progress to date". Drugs. 68 (11): 1483–91. doi:10.2165/00003495-200868110-00002. PMID 18627206. S2CID 46960558.
  2. ↑ Wong SS, Webby RJ (July 2013). "Traditional and new influenza vaccines". Clinical Microbiology Reviews. American Society for Microbiology. 26 (3): 476–92. doi:10.1128/cmr.00097-12. PMC 3719499. PMID 23824369.
  3. ↑ "Vaccines Protect You". Vaccines.gov. Retrieved 18 December 2018.
  4. ↑ Nabel GJ (February 2013). "Designing tomorrow's vaccines". The New England Journal of Medicine. 368 (6): 551–60. doi:10.1056/nejmra1204186. PMC 3612922. PMID 23388006.
  5. ↑ Vlecken DH, Pelgrim RP, Ruminski S, Bakker WA, van der Pol LA (October 2013). "Comparison of initial feasibility of host cell lines for viral vaccine production". Journal of Virological Methods. 193 (1): 28–41. doi:10.1016/j.jviromet.2013.04.020. PMID 23684847.
  6. 1 2 "How Influenza (Flu) Vaccines Are Made". Centers for Disease Control and Prevention (CDC). 24 September 2018. Retrieved 18 December 2018.
  7. 1 2 Perdue ML, Arnold F, Li S, Donabedian A, Cioce V, Warf T, Huebner R (August 2011). "The future of cell culture-based influenza vaccine production". Expert Review of Vaccines. 10 (8): 1183–94. doi:10.1586/erv.11.82. PMID 21854311. S2CID 28477882.
  8. 1 2 Zahoor MA, Khurshid M, Qureshi R, Naz A, Shahid M (July 2016). "Cell culture-based viral vaccines: current status and future prospects". Future Virology. 11 (7): 549–62. doi:10.2217/fvl-2016-0006.
  9. ↑ Audsley JM, Tannock GA (2008). "Cell-based influenza vaccines: progress to date". Drugs. 68 (11): 1483–91. doi:10.2165/00003495-200868110-00002. PMID 18627206. S2CID 46960558.
  10. ↑ "FDA clears first cell-based flu vaccine". Center for Infectious Disease Research and Policy. 21 November 2012. Retrieved 24 September 2013.
  11. ↑ "Vaccine Production in Cells". Flu.gov. 2006-07-17. Retrieved 2013-09-24.^[verification needed]
  12. 1 2 "Cell-Based Flu Vaccines". Centers for Disease Control and Prevention (CDC). 4 October 2018. Retrieved 19 December 2018.
  13. 1 2 Milián E, Kamen AA (2015). "Current and emerging cell culture manufacturing technologies for influenza vaccines". BioMed Research International. 2015: 504831. doi:10.1155/2015/504831. PMC 4359798. PMID 25815321.
  14. ↑ "FDA approves new seasonal influenza vaccine made using novel technology" (Press release). U.S. Food and Drug Administration (FDA). 16 January 2013. Archived from the original on 18 May 2013.
  15. ↑ "FDA approves first flu vaccine grown in insect cells". CIDRAP. 14 October 2019. Archived from the original on 14 October 2019. Retrieved 14 October 2019.
  16. ↑ "Flublok". U.S. Food and Drug Administration (FDA). 26 February 2018. STN 125285. Archived from the original on 14 October 2019. Retrieved 14 October 2019.
  17. ↑ "Flublok Quadrivalent". U.S. Food and Drug Administration (FDA). 2 August 2019. STN 125285. Archived from the original on 14 October 2019. Retrieved 14 October 2019.
  18. ↑ "20 November 2012 Approval Letter- Flucelvax". U.S. Food and Drug Administration (FDA). 20 November 2012. Archived from the original on 23 July 2017. Retrieved 19 August 2017.
  19. ↑ "Summary Basis of Regulatory Action". Food and Drug Administration (FDA). 23 May 2016. Retrieved 27 June 2019. Flucelvax was approved for active immunization against influenza for use in adults 18 years of age and older on 20 November 2012.
  20. ↑ "FDA approves first seasonal influenza vaccine manufactured using cell culture technology" (Press release). U.S. Food and Drug Administration (FDA). 20 November 2012. Archived from the original on 2 January 2013.
  21. ↑ Center for Biologics Evaluation and Research. "Approved Products – 20 November 2012 Approval Letter- Flucelvax". U.S. Food and Drug Administration (FDA). Archived from the original on 3 December 2012.
  22. 1 2 "Flucelvax Quadrivalent". U.S. Food and Drug Administration (FDA). 19 September 2019. STN BL 125408. Archived from the original on 17 October 2019. Retrieved 16 October 2019.
  23. ↑ "Flucelvax Product Information" (PDF). Food and Drug Administration (FDA). February 2013. Retrieved 10 November 2013.
  24. 1 2 Doroshenko A, Halperin SA (June 2009). "Trivalent MDCK cell culture-derived influenza vaccine Optaflu (Novartis Vaccines)". Expert Review of Vaccines. Informa UK Limited. 8 (6): 679–88. doi:10.1586/erv.09.31. PMID 19485748. S2CID 207223652.
  25. ↑ "Summary Basis of Regulatory Action" (PDF). Food and Drug Administration (FDA). 20 November 2012. Archived from the original (PDF) on 11 March 2016. Retrieved 10 September 2015. The main differences in manufacturing between Flucelvax and Optaflu are limited to minor differences in release specifications and the methods used to calculate HA concentration.
  26. 1 2 3 "Is Egg-based Vaccine Manufacturing on its Way Out?". The Cell Culture Dish. 4 October 2011. Retrieved 9 October 2017.
  27. ↑ Toovey S (November 2007). "Preventing rabies with the Verorab vaccine: 1985-2005 Twenty years of clinical experience". Travel Medicine and Infectious Disease. 5 (6): 327–48. doi:10.1016/j.tmaid.2007.07.004. PMID 17983973.
  28. ↑ "Ixiaro". European Medicines Agency. 15 March 2019. Retrieved 27 June 2019. The virus in Ixiaro is grown in mammal cells ('Vero cells') under laboratory conditions.

Further reading

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