Cell-based vaccine

To produce viral vaccines, candidate vaccine viruses are grown in mammalian, avian or insect tissue culture of cells with a finite lifespan.{{cite journal | vauthors = Vlecken DH, Pelgrim RP, Ruminski S, Bakker WA, van der Pol LA | title = Comparison of initial feasibility of host cell lines for viral vaccine production | journal = Journal of Virological Methods | volume = 193 | issue = 1 | pages = 28–41 | date = October 2013 | pmid = 23684847 | doi = 10.1016/j.jviromet.2013.04.020 }} These cells are typically Madin-Darby Canine Kidney cells,{{cite web|url=https://www.cdc.gov/flu/vaccine-process/ |title=How Influenza (Flu) Vaccines Are Made |date=2018-09-24|publisher=Centers for Disease Control and Prevention (CDC)|access-date=2018-12-18}} 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.{{cite journal | vauthors = Perdue ML, Arnold F, Li S, Donabedian A, Cioce V, Warf T, Huebner R | s2cid = 28477882 | title = The future of cell culture-based influenza vaccine production | journal = Expert Review of Vaccines | volume = 10 | issue = 8 | pages = 1183–94 | date = August 2011 | pmid = 21854311 | doi = 10.1586/erv.11.82 }} 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. Next, the selected virus is inoculated into cultured cells and the virus allowed to replicate for some time. Then, the virus-containing fluid is collected from the cells and the virus antigen is purified, the viruses inactivated, and the product tested.

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.{{cite journal | vauthors = Zahoor MA, Khurshid M, Qureshi R, Naz A, Shahid M | title = Cell culture-based viral vaccines: current status and future prospects. | journal = Future Virology | date = July 2016 | volume = 11 | issue = 7 | pages = 549–62 | doi = 10.2217/fvl-2016-0006 }} 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.{{cite journal | vauthors = Audsley JM, Tannock GA | s2cid = 46960558 | title = Cell-based influenza vaccines: progress to date | journal = Drugs | volume = 68 | issue = 11 | pages = 1483–91 | date = 2008-08-01 | pmid = 18627206 | doi = 10.2165/00003495-200868110-00002 | doi-access = free }} 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. In addition, some strains do not grow well on embryonic chicken eggs.

Cell lines grown in synthetic media avoid animal serum, which may pose a sterility problem, more specifically, preventing the spread of transmissible spongiform encephalopathies.{{cite journal |vauthors=Audsley JM, Tannock GA |s2cid=46960558 |title=Cell-based influenza vaccines: progress to date |journal=Drugs |volume=68 |issue=11 |pages=1483–91 |date=2008 |pmid=18627206 |doi=10.2165/00003495-200868110-00002|doi-access=free }}{{cite web|url=http://www.cidrap.umn.edu/news-perspective/2012/11/fda-clears-first-cell-based-flu-vaccine |title=FDA clears first cell-based flu vaccine |publisher=Center for Infectious Disease Research and Policy |date=2012-11-21 |accessdate=2013-09-24}} {{verify source |date=September 2019 |reason=This ref was deleted Special:Diff/874396241 by a bug in VisualEditor and later restored by a bot from the original cite located at Special:Permalink/871365452 cite #3 - verify the cite is accurate and delete this template. User:GreenC bot/Job 18}}"Vaccine Production in Cells". Flu.gov. 2006-07-17. Retrieved 2013-09-24.^[verification needed] {{verify source |date=September 2019 |reason=This ref was deleted Special:Diff/874396241 by a bug in VisualEditor and later restored by a bot in plain-text form. The original cite can be found at Special:Permalink/871365452 (or in a rev close it it) as cite #4 - find and verify the cite and replace this template with it (4). User:GreenC bot/Job 18}} 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.{{cite web|url=https://www.cdc.gov/flu/prevent/cell-based.htm |title=Cell-Based Flu Vaccines |date=2018-10-04|publisher=Centers for Disease Control and Prevention (CDC)|access-date=2018-12-19}}

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.{{cite journal | vauthors = Milián E, Kamen AA | title = Current and emerging cell culture manufacturing technologies for influenza vaccines | journal = BioMed Research International | volume = 2015 | pages = 504831 | year = 2015 | pmid = 25815321 | pmc = 4359798 | doi = 10.1155/2015/504831 | doi-access = free }}{{cite press release | url = https://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm335891.htm | title = FDA approves new seasonal influenza vaccine made using novel technology | date = 16 January 2013 | archive-url = https://web.archive.org/web/20130518014553/https://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm335891.htm | archive-date = 18 May 2013 | url-status = dead | publisher = U.S. Food and Drug Administration (FDA)}}{{cite web | title = FDA approves first flu vaccine grown in insect cells | website = CIDRAP | date = 14 October 2019 | url = http://www.cidrap.umn.edu/news-perspective/2013/01/fda-approves-first-flu-vaccine-grown-insect-cells | archive-url = https://web.archive.org/web/20191014200136/http://www.cidrap.umn.edu/news-perspective/2013/01/fda-approves-first-flu-vaccine-grown-insect-cells | archive-date = 14 October 2019 | url-status = live | access-date = 14 October 2019 }}{{cite web | title = Flublok | website = U.S. Food and Drug Administration (FDA) | date = 26 February 2018 | url = https://www.fda.gov/vaccines-blood-biologics/vaccines/flublok | archive-url = https://web.archive.org/web/20191014200957/https://www.fda.gov/vaccines-blood-biologics/vaccines/flublok | archive-date = 14 October 2019 | url-status = dead | access-date = 14 October 2019 | id = STN 125285 }}{{cite web | title = Flublok Quadrivalent | website = U.S. Food and Drug Administration (FDA) | date = 2 August 2019 | url = https://www.fda.gov/vaccines-blood-biologics/vaccines/flublok-quadrivalent | archive-url = https://web.archive.org/web/20191014201325/https://www.fda.gov/vaccines-blood-biologics/vaccines/flublok-quadrivalent | archive-date = 14 October 2019 | url-status = dead | access-date = 14 October 2019 | id = STN 125285 }}

In 2012, the US FDA approved Flucelvax as the first mammalian cell-based Influenza vaccine in the United States.{{cite web | url = https://www.fda.gov/BiologicsBloodVaccines/Vaccines/ApprovedProducts/ucm328684.htm | title = 20 November 2012 Approval Letter- Flucelvax | publisher = U.S. Food and Drug Administration (FDA) | date = 20 November 2012 | access-date = 19 August 2017 | archive-url = https://web.archive.org/web/20170723030346/https://www.fda.gov/BiologicsBloodVaccines/Vaccines/ApprovedProducts/ucm328684.htm | archive-date = 23 July 2017 | url-status = dead }}{{cite web | url = https://www.fda.gov/media/122724/download | archive-url = https://web.archive.org/web/20191214113132/https://www.fda.gov/media/122724/download | url-status = dead | archive-date = 14 December 2019 | title = Summary Basis of Regulatory Action | publisher = Food and Drug Administration (FDA) | date = 23 May 2016 | access-date = 27 June 2019 | quote = Flucelvax was approved for active immunization against influenza for use in adults 18 years of age and older on 20 November 2012.}} The vaccine was produced by Novartis through culturing of the Madin-Darby canine kidney cell line.{{cite press release | publisher = U.S. Food and Drug Administration (FDA) | title = FDA approves first seasonal influenza vaccine manufactured using cell culture technology | url = https://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm328982.htm | date = 20 November 2012 | url-status = dead | archive-url = https://web.archive.org/web/20130102094936/https://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm328982.htm | archive-date = 2 January 2013 }}{{cite web | url = https://www.fda.gov/BiologicsBloodVaccines/Vaccines/ApprovedProducts/ucm328684.htm | title = Approved Products – 20 November 2012 Approval Letter- Flucelvax | author = Center for Biologics Evaluation and Research | publisher = U.S. Food and Drug Administration (FDA) | url-status = dead | archive-url = https://web.archive.org/web/20121203114226/https://www.fda.gov/BiologicsBloodVaccines/Vaccines/ApprovedProducts/ucm328684.htm | archive-date = 3 December 2012}} Specifically, Flucelvax targets four Influenza sub-types which includes Influenza A subtype H1N1, Influenza A subtype H3N2, and two Influenza B viruses.{{cite web | title = Flucelvax Quadrivalent | website = U.S. Food and Drug Administration (FDA) | date = 2019-09-19 | url = https://www.fda.gov/vaccines-blood-biologics/vaccines/flucelvax-quadrivalent | archive-url = https://web.archive.org/web/20191017001731/https://www.fda.gov/vaccines-blood-biologics/vaccines/flucelvax-quadrivalent | archive-date = 17 October 2019 | url-status = live | access-date = 16 October 2019 | id = STN BL 125408 }} The vaccine is approved for people over the age of three years. As of 2013, Flucelvax had shown similar levels of vaccine efficacy and immunogenicity as traditional egg-based vaccines.{{cite web|url=https://www.fda.gov/downloads/BiologicsBloodVaccines/Vaccines/ApprovedProducts/UCM329134.pdf |archive-url=https://web.archive.org/web/20130226112311/http://www.fda.gov/downloads/BiologicsBloodVaccines/Vaccines/ApprovedProducts/UCM329134.pdf |url-status=dead |archive-date=26 February 2013 |title=Flucelvax Product Information |publisher=Food and Drug Administration (FDA) |date=February 2013 |access-date=2013-11-10}}

Optaflu, produced by Novartis, was approved by the European Medicines Agency in 2009, for use in countries affiliated with the European Union. Optaflu is nearly identical to Flucelvax; it is also produced in Madin-Darby canine kidney cells and targets the same Influenza subtypes.{{cite journal | vauthors = Doroshenko A, Halperin SA | s2cid = 207223652 | title = Trivalent MDCK cell culture-derived influenza vaccine Optaflu (Novartis Vaccines) | journal = Expert Review of Vaccines | volume = 8 | issue = 6 | pages = 679–88 | date = June 2009 | pmid = 19485748 | doi = 10.1586/erv.09.31 | publisher = Informa UK Limited }} 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.{{cite web |url=https://www.fda.gov/downloads/BiologicsBloodVaccines/Vaccines/ApprovedProducts/UCM332604.pdf |title=Summary Basis of Regulatory Action |publisher=Food and Drug Administration (FDA) |date=2012-11-20 |access-date=2015-09-10 |archive-url=https://web.archive.org/web/20160311074609/https://www.fda.gov/downloads/BiologicsBloodVaccines/Vaccines/ApprovedProducts/UCM332604.pdf|archive-date=11 March 2016|quote=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. |url-status=dead }}

The Food and Drug Administration approved two mammalian vero cell based vaccines for rotavirus, Rotarix by GlaxoSmithKline and RotaTeq by Merck.{{cite web |url=http://cellculturedish.com/2011/10/is-egg-based-vaccine-manufacturing-on-its-way-out/|title=Is Egg-based Vaccine Manufacturing on its Way Out?|publisher=The Cell Culture Dish |access-date=9 October 2017|date=2011-10-04}}

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

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

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

Verorab, developed by Sanofi Pasteur, is a mammalian vero cell based rabies vaccine approved by the World Health Organization.{{cite journal | vauthors = Toovey S | title = Preventing rabies with the Verorab vaccine: 1985-2005 Twenty years of clinical experience | journal = Travel Medicine and Infectious Disease | volume = 5 | issue = 6 | pages = 327–48 | date = November 2007 | pmid = 17983973 | doi = 10.1016/j.tmaid.2007.07.004 }}

Ixiaro by Valneva SE for Japanese encephalitis.{{cite web | url = https://www.ema.europa.eu/en/medicines/human/EPAR/ixiaro | title = Ixiaro | publisher = European Medicines Agency | date = 2019-03-15 | access-date = 27 June 2019 | quote = The virus in Ixiaro is grown in mammal cells ('Vero cells') under laboratory conditions.}}

{{reflist}}

• {{cite journal |vauthors=Pérez Rubio A, Eiros JM |title=Cell culture-derived flu vaccine: Present and future |journal=Hum Vaccin Immunother |volume=14 |issue=8 |pages=1874–1882 |date=2018 |pmid=29672213 |pmc=6149758 |doi=10.1080/21645515.2018.1460297}}

• [http://www.emro.who.int/entity/vpi/ WHO Vaccine preventable diseases and immunization]
• [https://www.cellosaurus.org/search?input=%22Vaccine%20production%20cell%20line%22 Cellosaurus list of cell lines that are/can be used for vaccine production]

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