Rubella vaccine

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Rubella virus

A rubella vaccine is a vaccine against infection with the rubella virus (RuV). The rubella vaccine is on the World Health Organization's list of Essential Medicines .

properties

The rubella vaccine is a live attenuated vaccine . It is based on an attenuated rubella virus strain ("vaccine strain"), which is multiplied and isolated in suitable tissue, and other accompanying substances. Possible vaccine strains are z. B. Cendehill (obsolete), HPV-77 (obsolete), Wistar RA 27/3 , Takahashi , Matsuura or TO-336 .

The first three rubella vaccines were approved in the United States in 1969:

  • The Meruvax vaccine developed by Maurice Hilleman ; the vaccine strain then used HPV-77 DE-5 was in duck embryos ( " d uck e mbryo") increases and is based on HPV-77 ( high passage virus - 77 times passaged), an originally in kidney cells by Western vervet attenuated (GMK) Vaccine strain through the work of Paul Parkman and Harry Meyer;
  • the Rubelogen vaccine , the corresponding vaccine strain HPV-77: DK12 , was propagated in kidney cells of dogs (" d og k idney");
  • and Cendevax , whose vaccine strain GMK-3: RK53 ( Cendelhill ) was grown in rabbit kidney cells (" r abbit k idney") ( GMK-3: RK53 by the work of Abel Prinzie and Constant Huygelen).

After approval of the monovalent rubella vaccine Meruvax II of MSD 1979, all vaccines mentioned above were the better because of the safety and efficacy profile above Meruvax-II taken off the market. It is based on the Wistar RA 27/3 vaccine strain , which, compared to the other vaccine strains, displays consistent immunogenicity , induces resistance to reinfection and has a low rate of side effects.

The rubella virus (R) of the “Wistar RA 27/3” vaccine strain used today was originally isolated in 1965 from the tissue of an aborted (A) fetus infected with rubella. In 1964 a rubella epidemic broke out in the USA, the origin of which was in Europe in 1963. As a result, many abortions due to rubella embryo fetopathy occurred in the United States ; the virus was finally isolated from the 27th aborted fetus of a third tissue sample (kidney cells). Then, this was developed by Stanley Plotkin at the Wistar Institute through 25 passages in the human embryonic fibroblasts - cell line WI-38 attenuated sequentially at 35, 33 and finally 30 ° C. A sequence comparison with the wild rubella virus shows that the vaccine strain Wistar RA 27/3 differs in 31 amino acids .

Most vaccines based on the Wistar RA 27/3 vaccine strain are now approved worldwide; only in Japan and China are other vaccine strains such as Matsuura , TO-336 or BRD-II used . In Germany, the Wistar RA 27/3 vaccine strain has also been used for the rubella component since the 1980s . In vaccines, the rubella viruses of the vaccine strain Wistar RA 27/3 are propagated either in human cell lines such as WI-38 (e.g. MM-RVaxPro, ProQuad) or MRC-5 (e.g. Priorix or Priorix-Tetra).

Nowadays rubella vaccines are usually part of the multiple vaccines MMR vaccine (approval USA 1971 and Germany 1980, together with a mumps and measles vaccine ) and MMRV vaccine (approval USA 2005 and Germany 2006, in addition with a varicella vaccine ). No individual rubella vaccine has been available in Germany since 2012.

immunology

After a vaccination, neutralizing antibodies are produced that protect against renewed rubella infection. The vaccine is usually given twice. After vaccination, immunity develops in 95% of those who are over 12 months old . More than 90% of those vaccinated are immune for at least 15 years, mostly for life. The seroconversion during a rubella vaccine alone or in a MMR or MMRV vaccine are similar.

Vaccine production

Human diploid cell cultures (MRC-5 or WI-38) are infected with the vaccine strain (e.g. Wistar RA 27/3 ). With Wistar RA 27/3 , the cell cultures are incubated at 30 ° C., after 4 to 7 days the virus-containing supernatant is removed and new medium is added. In this way, virus-containing medium can be obtained every two to three days for several weeks. Before lyophilization , a stabilizer (generally buffer salts, sucrose or sorbitol , glutamic acid or other amino acids ) is added to the virus-containing medium ; after lyophilization the vaccine is hypertonic .

The vaccine is quite durable. So the effectiveness remains at 4 ° C for at least 5 years. Only at room temperature does the vaccine lose its effectiveness after 3 months. The vaccine should be stored between 2 and 8 ° C in the dark.

application

The vaccines are lyophilized and are dissolved in 0.5 ml of water aq . It should then be applied within 8 hours. Each rubella vaccine contains at least 1000 ZKID 50 (cell culture infectious dose 50%) or PFU ( plaque forming units ) and accompanying substances such as human albumin and dextran . Traces of neomycin may be present.

The vaccine is given subcutaneously . Studies of other forms of administration (e.g. intranasal application or via an aerosol ) show no superiority over subcutaneous administration.

Side effects

Adverse drug reactions with mumps vaccines include pain at the injection site and one day flu-like symptoms.

There are no safety concerns against further MMR vaccination (s) with existing immunity to one of the components (“over-vaccination”), and a combined vaccination does not lead to increased undesirable effects.

Contraindications

Contraindications are pregnancy (including 4 weeks before pregnancy) and immunosuppression .

Trade names

Trade names for rubella vaccines are e.g. B. Meruvax II . The Meruvax I , Rubelogen and Cendevax , approved since 1969 , have not been used since 1979.

literature

Individual evidence

  1. ↑ WHO Model List of Essential Medicines . In: World Health Organization . October 2013. Retrieved April 22, 2014.
  2. ↑ a b c d e f g h i j Stanley A. Plotkin et al .: Plotkin's Vaccines . 7th edition. Elsevier, Philadelphia 2017, ISBN 978-0-323-35761-6 , pp. 979 ff . ( elsevier.com ).
  3. ↑ a b c d e Pinkbook Rubella, Epidemiology of Vaccine Preventable Diseases. In: CDC. September 25, 2019, accessed May 29, 2020 (American English).
  4. ↑ Jeanette Wilkins et al .: Viremia in a Recipient of HPV-77 Rubella Virus Vaccine . In: California Medicine . tape 110 , no. 3 , March 1969, p. 224-227 , PMID 5773481 , PMC 1503454 (free full text).
  5. ↑ a b Stanley A. Plotkin et al .: Plotkin's Vaccines . 7th edition. Elsevier, Philadelphia 2017, ISBN 978-0-323-35761-6 , pp. 11 ( elsevier.com ).
  6. ↑ a b Stanley A. Plotkin et al .: Attenuation of RA 27/3 Rubella Virus in WI-38 Human Diploid Cells . In: American Journal of Diseases of Children . tape 118 , no. 2 , August 1, 1969, p. 178-185 , doi : 10.1001 / archpedi.1969.02100040180004 .
  7. ^ Rubella (German Measles). In: WHO. January 10, 2014, accessed May 29, 2020 .
  8. ↑ A. Tischer and E. Gerike: Rötelnsituation in Deutschland . In: Federal Health Gazette . tape 43 , December 2000, p. 940–949 , doi : 10.1007 / s001030070012 ( rki.de [PDF; accessed on May 29, 2020]).
  9. ↑ SmPC MM-RVaxPro. (PDF) In: EMA. May 14, 2020, accessed May 29, 2020 .
  10. ↑ SmPC ProQuad. (PDF) February 26, 2020, accessed on May 29, 2020 .
  11. ↑ Priorix specialist information. November 2019, accessed May 29, 2020 .
  12. ↑ technical information Priorix-Tetra. December 2019, accessed May 29, 2020 .
  13. ^ Vaccine Timeline . Retrieved February 10, 2015.
  14. ↑ a b DISCUSSION ABOUT MEASURE VACCINATION In: Medicinal Telegram . 2013, accessed May 29, 2020 .
  15. ^ Deborah Mitchell, The Essential Guide to Children's Vaccines . St. Martin's Press, New York 2013, ISBN 978-1-466-82750-9 , p. 127.
  16. ↑ a b c Ulrich Heininger: Rubella . In: Heinz Spiess, Ulrich Heininger, Wolfgang Jilg (Eds.): Impfkompendium . 8th edition. Georg Thieme Verlag, 2015, ISBN 978-3-13-498908-3 , p. 263 .
  17. ↑ a b Procedure in women of childbearing potential to avoid rubella and varicella during pregnancy. In: RKI. December 13, 2018, accessed May 29, 2020 .
  18. ^ Robert Koch Institute: Communication from the Standing Vaccination Commission at the Robert Koch Institute: Recommendation and scientific justification for the alignment of the professionally indicated measles, mumps, rubella (MMR) and varicella vaccinations . In: Epidemiological Bulletin . No. 2 , January 9, 2020, p. 3–22 ( rki.de [PDF]).
  19. ↑ Mona Marin et al .: Prevention of varicella: Recommendations of the Advisory Committee on Immunization Practices (ACIP) . In: MMWR. Recommendations and reports: Morbidity and mortality weekly report. Recommendations and reports . tape 56 , RR-4, June 22, 2007, pp. 1-40 , PMID 17585291 .