Polio vaccine

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A polio vaccine is a vaccine for the prophylaxis of a by the poliovirus induced poliomyelitis . Two fundamentally different vaccines are available: since 1955 an inactivated polio vaccine developed by Jonas Salk , abbreviated IPV, and since 1961 an oral polio vaccine developed by Albert Sabin , abbreviated OPV. With the use of both vaccines, each with its own specific advantages and disadvantages, the number of poliomyelitis cases has been drastically reduced worldwide since the 1950s.

For the basic immunization of children and adolescents, only the inactivated polio vaccine has been used in Germany since 1998. The World Health Organization (WHO) and a number of other organizations aim to eradicate the polio virus worldwide through vaccinations with OPV and a subsequent switch to IPV as part of the Global Polio Eradication Initiative (GPEI) adopted in 1988.

Inactivated polio vaccine (Salk, IPV)

The inactivated polio vaccine according to Salk, a dead vaccine , is currently the vaccine routinely used in Europe.

Manufacturing

TEM image of poliovirus

Virulent polioviruses of types 1, 2 or 3 are propagated by cell culture in Vero cells , an established cell line from kidney cells of the green monkey , alternatively also in human diploid cells. A purified virus suspension is generated from the culture medium by filtration , ultrafiltration and chromatography . The careful separation of cell components is a prerequisite for complete virus inactivation . This is done by treatment with formaldehyde for several days ; the chemical reaction of formaldehyde with virus components means that the virus loses its ability to replicate. After no more infectious viruses can be detected, the remaining formaldehyde is removed. The test for non-inactivated viruses is carried out in a cell culture test, the detection of the antigen content is carried out with an ELISA test, often supplemented by animal experiments with rats, which have to develop protective antibodies after a test vaccination .

The finished vaccine, monovalent or one of the combinations of inactivated polioviruses of types 1, 2 and / or 3, often still contains traces of antibiotics such as neomycin or streptomycin .

application

The inactivated polio vaccine is injected intramuscularly . Today the vaccine is often used as part of a combination vaccine, for example a hexavalent vaccine . It can also be used in patients with an immunodeficiency as it does not contain an infectious virus. On the one hand, infants born to mothers who have transferred their polio antibodies to the unborn child via the placenta ("loan antibodies") are initially protected from polio; on the other hand, their vaccination does not lead to the formation of their own antibodies sufficiently during this time. Therefore, according to the STIKO vaccination calendar , the basic immunization against the poliovirus does not start until the age of 2 months. When using combination vaccines with a pertussis component (AP), it usually comprises 3 doses in the 1st year of life and a further dose at the beginning of the 2nd year of life. If no combination vaccine is used, two or three vaccinations are given in the 1st and 2nd year of life, depending on the vaccine. A booster vaccination with an IPV-containing vaccine is recommended for ages 9-17. A basic immunization started with OPV is completed with IPV.

Side effects

There are hardly any side effects when using the inactivated polio vaccine . They are usually limited to pain at the injection site.

Contraindications

The vaccine should not be used if there is a known severe allergy to any of the ingredients. Vaccination should also not be given during an acute, serious or febrile illness.

effect

The IPV protects almost all vaccinated persons from the serious consequences of the infection, in particular paralysis, after two vaccinations, largely regardless of boundary conditions (hygiene, nutritional status, diarrheal diseases), provided the first vaccination does not occur until or shortly after the 8th week after birth and the second Vaccination takes place after another 8 weeks at the earliest. Even in a country with restricted hygienic conditions like Puerto Rico , after three vaccinations (two, four and 6 months after birth), over 99.5% of those vaccinated have protective antibodies against all three types of poliovirus. This protection presumably lasts for decades. In adulthood, a routine refreshment of the vaccination protection is therefore only recommended for people with an increased risk of developing polio. This includes people planning a trip to an endemic area , but also medical staff. The repeated administration of IPV leads to an increase in the immunity of the mucous membranes, but this booster effect is significantly lower than that after OPV vaccinations. For this reason, people vaccinated with IPV do not acquire reliable protection against the ingestion of polio viruses, especially through the intestines, for example from contaminated drinking water. You can continue to be infected with polio viruses without symptoms or with few symptoms, multiply them and excrete them unnoticed, especially through the intestines, and thus spread them to third parties under unfavorable hygienic conditions. This was the result of an investigation into the outbreak of a polio epidemic in Israel in 2013.

Manufacturing risk

Viruses capable of replication are used to produce the IPV. The safety requirements for vaccine manufacturers are correspondingly high. The WHO recommends Biological Protection Level 3 / Polio for IPV manufacturing facilities after the wild virus has been eradicated . A possible solution to this problem could be the use of attenuated viruses to produce the inactivated polio vaccine.

Oral polio vaccine (Sabin, OPV)

Administration of an oral polio vaccine

The oral polio vaccine of Sabin, a live vaccine for polio vaccine , the vaccine has long been used in most of Europe; only in Scandinavia and the Netherlands was the inactivated vaccine continuously used. The use of the oral polio vaccine has not been recommended in Europe since 1998, as this vaccine creates an extremely low risk of vaccine poliomyelitis . However, because of its effectiveness, low cost and ease of use, the oral polio vaccine is still used in polio-prevalent countries to contain and eradicate the pathogen. Complete protection against paralysis by the virus is usually achieved after four vaccinations.

Manufacturing

The oral polio vaccine is also propagated in cell cultures, mostly in human diploid cells. However, special, weakened viruses of types 1, 2 and I3 are not used here. These polioviruses have a large number of mutations in the genome that mean that infection with these viruses no longer causes poliomyelitis. For attenuation , human polioviruses of types 1 and 3 were propagated in several dozen passages in monkeys, partly at low temperatures in cell cultures, partly in living animals. This resulted in spontaneous mutations; those that reduced virulence were selected and further bred. Type 2 used a naturally occurring, attenuated virus that had been isolated from the stool of a healthy child.

Molecular analyzes later showed that mutations in the internal ribosomal entry point in the 5 'untranslated region of the virus genome are responsible for the loss of neurovirulence in all vaccine viruses . The mutated virus cannot multiply in nerve cells; however, reproduction in the intestine is not impaired.

Reference cultures of the vaccine viruses, which can be traced back to the attenuated virus strains used by Sabin, are made available by the World Health Organization for vaccine production; the manufacturers propagate these viruses in a seed system. The viruses for each type are cultivated individually in cell culture at 33 to 35 ° C. and purified by filtration; the virus suspension obtained in this way is then tested for disease-causing viruses to be on the safe side. For decades, each batch of the vaccine had to be tested in rhesus monkeys for this purpose . A neurovirulence test in transgenic mice that carry a human receptor (CD155) for the poliovirus was only approved by the World Health Organization in 2000 . After the test, the preparations of the individual virus types are mixed. Oral polio vaccines often contain traces of antibiotics such as neomycin.

Recently, vaccines with only one virus (monovalent OPV, "mOPV") or two virus types (bivalent OPV, "bOPV") have been produced and used, for example in some regions of India where only type 1 is endemic, as mOPV1 .

Application and effect

The oral polio vaccine is as oral vaccination applied; the vaccine is often given on a lump of sugar, which is then swallowed. After regular use and under favorable conditions, the vaccination leads to a silent celebration in almost 100% of the vaccinated people , since after an infection of the gastrointestinal tract without symptoms of disease, antibodies reliably protect against paralysis not only in the blood, but also in the form of IgA in the mucous membranes of the intestine. Since the vaccine virus is partially excreted after vaccination, contact persons can also be infected by the vaccine virus, who in this way also gain vaccination protection. The oral polio vaccine can thus produce herd immunity . This explains that the actual efficiency of the OPV campaigns, especially in developing countries, was higher than expected due to the sometimes unfavorable boundary conditions there. For this reason, in countries where the poliovirus still occurs, the live vaccine is still used, at least at the beginning of vaccination campaigns , despite the known restrictions and risks from VAPP and VDPV . In addition, the oral vaccine is inexpensive to manufacture and easy to use.

In Germany and many other polio-free countries, the oral polio vaccine is no longer used on a regular basis because of its risks from VAPP and VDPV ; it is only intended to be used as a bar vaccine in the event of polio outbreaks after being brought in from abroad. The use of the live vaccine will also be discontinued worldwide in the medium term after the goal of eradicating the wild virus has been achieved.

Influence of unfavorable boundary conditions

The actual efficiency of the OPV is mainly reduced by:

  • maternal loan antibodies in newborns (also disadvantageous in IPV),
  • poor intestinal immune competence in malnourished children,
  • Diarrhea and intestinal infections,
  • limited quality of the vaccine (cold chain)

Such unfavorable conditions can significantly reduce the actual effectiveness of OPV campaigns. In Ghana, after three times OPV, neutralizing antibodies against all 3 poliovirus types were detected in only about 60% of the vaccinated.

Contraindications, side effects and risks

The live vaccine must not be used in people with immunodeficiency; It should also not be used on people who have contact with people with immunodeficiency. Hypersensitivity to one of the ingredients is also an exclusion criterion. In the event of acute febrile illnesses or intestinal disorders, vaccination should be postponed. The high incidence of diarrhea in children is one of the reasons why polio is difficult to eradicate in countries like India. In the case of diarrhea, the vaccination is often not effective.

The most common side effects are headache, vomiting, or diarrhea. An extremely rare risk of oral polio vaccine is vaccine-associated paralytic poliomyelitis ( VAPP ), which occurs after about 1 in 2.7 million doses of the vaccine and is at least in some cases caused by an immunodeficiency . With VAPP, persistent paralysis occurs for a period of at least six weeks. Clinically, the symptoms cannot be differentiated from those after wild virus infection. VAPP can be done after a recent OPV administration. But not only the vaccinated person, but also people who are exposed to the vaccine (for example close friends or spouses) can develop a VAPP. After an OPV application, only transient poliomyelitis can occasionally be observed.

In Germany, there were one or two cases of VAPP annually during the vaccination campaigns with OPV. The last VAPP occurred in 2000. However, it was not a classic VAPP, as the patient had already been vaccinated with OPV two years earlier (1998).

In even rarer cases, the virus after OPV can reverse mutate to a variant pathogenic to humans as part of its replication and then circulate in the population ( circulating vaccine-derived poliovirus, cVDPV ). The vast majority of VDPV cases are caused by type 3 vaccine viruses; this type is genetically less stable than the others. VDPV were reliably detected for the first time in 2001 in Haiti and the Dominican Republic in 21 cases; there are now a number of such examples from other countries. The largest case to date with 69 children suffering from cVDPV became known in 2007 in Nigeria. The cVDPV cases are mostly polioviruses of types 1 or 2. In 2019, a first case of polio in decades in the Philippines was also attributed to cVDPV by the WHO.

history

Spread of poliomyelitis in 2006
♦  Endemic areas
♦  Sporadic diseases
♦  Risk of reintroduction
Announcement of a polio vaccination campaign (and the administration of vitamin A and antiparasitic drugs) for children from 0 to 5 years in October 2017 in Dimbokro, Ivory Coast

Since the 1930s there have been attempts to produce a polio vaccine, mostly with viruses that have been inactivated by formaldehyde. However, these were not effective. It was not until 1954 that an inactivated polio vaccine manufactured by Salk and co-workers could be tested in a large randomized clinical trial with several hundred thousand children in the USA . The vaccine was approved immediately after the study results were announced in 1955.

A few weeks after the routine use of the inactivated vaccine in the USA began, a serious incident occurred. Non-inactivated polioviruses got into the vaccine due to deficiencies in production. Hundreds of thousands of children were infected as a result, 51 cases of permanent paralysis and five deaths. This cutter incident , named after the manufacturer Cutter Laboratories, is considered to be one of the most serious drug scandals in the USA. Investigations showed that remains of cell culture cells in the virus suspension had prevented complete inactivation by formaldehyde.

In parallel with Salk, several scientists developed oral polio vaccines, including Albert Sabin. The first studies with the Sabin vaccine were carried out from 1957, the first approval was in the USA in 1961, since 1963 a triple vaccine against all three virus types was approved. This quickly became the standard in many countries around the world, until in the late 1990s many developed countries reverted to using the inactivated vaccine after countries were declared polio-free.

Both the inactivated vaccine and the oral vaccine were partially contaminated with a simian virus, SV40 virus, until the early 1960s . Several million people may have come into contact with SV40 in this way; however, there is no adequate evidence that this led to disease.

Since 1988 the World Health Organization has set itself the goal of eradicating the poliovirus through a global vaccination campaign. Even if the original goal of achieving this by 2000 was not achieved, large parts of the world were successfully declared polio-free. The type 2 poliovirus has not been detected since 1999. In 2007 there were 1,310 cases of wild virus poliomyelitis worldwide. In 2008, type 1 and 3 viruses were still endemic in four countries: Nigeria, India, Pakistan, and Afghanistan. On May 5, 2014, the World Health Organization (WHO) declared a “Public Health Emergency of International Concern [PHEIC]” in response to the increasing spread of polio and recommended early booster vaccinations against polio for certain constellations. These recommendations, some of which are temporary, are made available on the information page of the Federal Foreign Office. In 2015, type 2 was declared eradicated by the WHO. In April 2016, a coordinated program was started to gradually convert the use of oral vaccines with viruses of all three strains, initially to oral vaccines with only types 1 and / or 3, and then to prevent reverse mutations to human pathogenic cVDPV, oral vaccines as a whole to be replaced by IPV, which now only contain types 1 and 3. On World Polio Day 2019, the WHO also declared type 3 to be eradicated.

Since 2000, more than 3 billion children have been vaccinated against polio.

literature

Individual evidence

  1. ^ A b T. Jacob John: Role of injectable and oral polio vaccines in polio eradication , online January 9, 2014, accessed October 10, 2019, https://doi.org/10.1586/14760584.8.1.5
  2. ^ A b Matthew R. Behrend et al .: A quantitative survey of the literature on poliovirus infection and immunity . In: International journal of infectious diseases: IJID: official publication of the International Society for Infectious Diseases . tape January 18 , 2014, p. 4-13 , doi : 10.1016 / j.ijid.2013.09.005 , PMID 24246740 .
  3. ^ Global Polio Eradication Initiative
  4. ↑ a b c WHO: Poliomyelitis and Vaccines to Eradicate it - Questions and Answers , online April 8, 2016
  5. ↑ a b Technical information from the WHO on the manufacture of polio vaccines
  6. ↑ a b c d Leaflet on Poliomyelitis from the Robert Koch Institute
  7. ↑ Robert Koch Institute: Vaccination against poliomyelitis: Frequently asked questions and answers - OPV versus IPV , as of November 8, 2013, accessed September 20, 2019
  8. ↑ ECDC: Epidemiological update: Polio virus in sewage and human faecal samples in Israel, August 2013 , online August 20, 2013, accessed September 20, 2019
  9. ↑ Robert Koch Institute: Epidemiological Bulletin 47/2013 , accessed September 20, 2019
  10. ↑ a b Olen M. Kew et al .: Vaccine-derived polioviruses and the endgame strategy for global polio eradication . In: Annual Review of Microbiology . tape 59 , 2005, pp. 587-635 , doi : 10.1146 / annurev.micro.58.030603.123625 , PMID 16153180 .
  11. ^ Nidia H. De Jesus: Epidemics to eradication: the modern history of poliomyelitis . In: Virology Journal . tape 4 , July 10, 2007, p. 70 , doi : 10.1186 / 1743-422X-4-70 , PMID 17623069 , PMC 1947962 (free full text).
  12. ↑ Eugenia Dragunsky et al .: Transgenic mice as an alternative to monkeys for neurovirulence testing of live oral poliovirus vaccine: validation by a WHO collaborative study . In: Bulletin of the World Health Organization . tape 81 , no. 4 , 2003, p. 251-260 , PMID 12764491 , PMC 2572431 (free full text).
  13. ↑ WHO: Oral Poliomyelitis Vaccine (OPV) - Questions & Answers (Q&A) - Production, Control and Prequalification process (PQ) , July 2012
  14. ↑ a b Nicholas C. Grassly et al .: Protective efficacy of a monovalent oral type 1 poliovirus vaccine: a case-control study . In: Lancet (London, England) . tape 369 , no. 9570 , April 21, 2007, p. 1356-1362 , doi : 10.1016 / S0140-6736 (07) 60531-5 , PMID 17448821 .
  15. ↑ a b WHO: Weekly epidemiological record, issue 91 No. 12 from March 2016, pages 145-168, pdf (597 kB) [1]
  16. ↑ Joseph Kl Opare et al .: Poliovirus neutralizing antibody levels among individuals in three regions of Ghana . In: Ghana Medical Journal . tape 53 , no. 2 , June 2019, p. 170–180 , doi : 10.4314 / gmj.v53i2.13 , PMID 31481814 , PMC 6697761 (free full text).
  17. ↑ a b Burghard Stück et al .: New vaccination strategy against poliomyelitis: live vaccines or inactivated vaccines? Deutsches Ärzteblatt , October 17, 1997, accessed on January 7, 2020 .
  18. ↑ Lauren R. Platt et al .: Vaccine-Associated Paralytic Poliomyelitis: A Review of the Epidemiology and Estimation of the Global Burden . In: The Journal of Infectious Diseases . tape 210 , suppl_1, November 1, 2014, p. S380-S389 , doi : 10.1093 / infdis / jiu184 .
  19. ↑ Epidemiological Bulletin 7/2002 - Vaccine-preventable diseases in Germany up to the year 2000. (PDF) RKI, February 15, 2002, accessed on January 7, 2020 .
  20. ↑ Vaccine-derived polio in Nigeria. In: Lancet. 2007 Oct 20; 370 (9596), p. 1394, PMID 17950846 .
  21. ↑ First case of polio in the Philippines for decades , Deutsches Ärzteblatt, online September 19, 2019, accessed September 22, 2019
  22. ^ Paul A. Offit: The Cutter incident, 50 years later . In: The New England Journal of Medicine . tape 352 , no. 14 , April 7, 2005, pp. 1411-1412 , doi : 10.1056 / NEJMp048180 , PMID 15814877 .
  23. ↑ Danielle L. Poulin and James A. DeCaprio: Is there a role for SV40 in human cancer? In: Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology . tape 24 , no. 26 , September 10, 2006, pp. 4356-4365 , doi : 10.1200 / JCO.2005.03.7101 , PMID 16963733 .
  24. ↑ Centers for Disease Control and Prevention (CDC): Progress toward interruption of wild poliovirus transmission - worldwide, January 2007-April 2008 . In: MMWR. Morbidity and mortality weekly report . tape 57 , no. 18 , May 9, 2008, pp. 489-494 , PMID 18463607 .
  25. ↑ Current travel medical information (as of 2019). Federal Foreign Office , June 18, 2019, accessed on October 13, 2019 .
  26. ↑ Two out of three wild poliovirus strains eradicated: Global eradication of wild poliovirus type 3 declared on World Polio Day , online October 24, 2019, accessed October 24, 2019
  27. ↑ Dr Thomas Schmitz, Sven Siebert: Plain text: Vaccination! - An educational book to protect our health . 1st edition. HarperCollins, 2019, ISBN 978-3-95967-884-1 , pp. 125 .