Poliomyelitis

Poliomyelitis is an acute communicable disease of humans caused by a human enterovirus of the Picornaviridae family. The virus is composed of a single-stranded, positive-sense RNA genome and a protein capsid. The 3 serotypes of poliovirus carry are antigenically distinct. Poliovirus is transmitted from one person to another by oral contact with secretions or faecal material from an infected person. Most poliovirus infections cause asymptomatic viral replication that is limited to the alimentary tract. However, following an incubation period of approximately 7–10 days (range, 4–35 days), about 24% of those infected develop clinical signs such as fever, headache and sore throat (considered a minor illness).

Paralytic poliomyelitis, experienced in less than 1% of poliovirus infections, occurs when the virus enters the central nervous system and replicates in anterior horn cells (motor neurons) of the spinal cord. When it multiplies in the nervous system, the virus can destroy nerve cells (motor neurons) which activate skeletal muscles. The affected muscles lose their function due to a lack of nervous enervation, a condition known as acute flaccid paralysis. In the most severe cases (bulbar polio), poliovirus attacks the motor neurons of the brain stem, reducing breathing capacity and causing difficulty in swallowing and speaking. Without respiratory support, bulbar polio can result in death. Polio can strike at any age, but affects mainly children under three.

In May 1988 the World Health Assembly resolved to eradicate polio from the world. As a result of this eradication program, the number of poliomyelitis cases have been reduced by over 99%, and the endemic circulation type 2 virus has been halted. However, a small number of countries have not yet succeeded in stopping endemic transmission of polio, resulting in small sporadic outbreaks caused by travellers. When poliovirus transmission is successfully halted, a globally coordinated programme of containment of remaining wild poliovirus stocks and a discontinuation of the live oral polio vaccine will be required.

Polio Vaccines

Poliovirus infection can provide lifelong immunity against the disease, but this protection is limited to the serotype involved. Infection with one type does not protect an individual against infection with the other two types. The development of effective vaccines to prevent paralytic polio was one of the major medical breakthroughs of the 20th century. Two different kinds of vaccine are available, an inactivated (killed) polio vaccine (IPV) and a live attenuated oral polio vaccine (OPV). The presence of neutralizing antibody against polioviruses is considered a reliable correlate of protection against poliomyelitis. However, immunity induced by one serotype does not provide protection against the other two serotypes.

Inactivated polio vaccine was first introduced in 1955 and is produced from wild-type poliovirus strains of each serotype that have been inactivated (killed) with formalin. As an injectable vaccine, it can be administered alone or in combination with other vaccines (e.g., diphtheria, tetanus, pertussis, hepatitis B, and haemophilus influenza). IPV has been used successfully to eradicate polio in a few countries, notably in Scandinavia and the Netherlands. In the numerous countries that have introduced to IPV over the last decade no evidence of continued circulation of poliovirus strains has been observed, indicating that IPV may successfully inhibit community transmission of poliovirus. Adverse events following administration of IPV are very mild and transient, and because it is a killed vaccine, there is no risk of the live-virus-associated risks associated with OPV use. However, due to the risks associated with the large quantities of wild-type poliovirus(WPV) needed for IPV production, following the global cessation of poliovirus transmission high level containment of all manufacturing and quality control areas where live virus is handled must be implemented. Efforts are now under way to develop a new, inactivated polio vaccine more suited to the post-eradication environment. One such candidate is an inactivated vaccine produced from the attenuated Sabin strains.

Oral polio vaccine was first introduced in 1961 and consists of a mixture of the three live attenuated poliovirus serotypes (Sabin types 1, 2 and 3), selected for their lower neurovirulence and reduced transmissibility. In addition to trivalent OPV (tOPV), which is used in many countries for routine or supplemental vaccination, monovalent OPVs, against type-1 (mOPV1) and against type-3 (mOPV3), have been licensed since 2005 for use in some countries. Monovalent OPVs against type-2 have been licensed, but are expected to be used primarily for stockpiles. In 2009, 2 bivalent (type-1 and type-3) OPVs (bOPVs) were licensed. The mOPVs and bOPVs are used primarily during mass campaigns. In the end-stages of stopping endemic transmission, monovalent OPV containing only attenuated virus of one serotype has been increasingly employed to target areas where one serotype predominates. Three or more spaced doses of OPV normally generate a protective immune response against subsequent infections, although in some areas additional doses (seven or more) may be required to prevent paralytic disease.

Following oral administration OPV strains produce a local immune response in the lining of the intestines which is the primary site for poliovirus replication. Mucosal immunity decreases the replication and excretion (shedding) of the virus, and thus provides a potential barrier to its transmission. This mechanism, combined with the ease of oral administration and the very low cost of the vaccine, have made it the vaccine of choice for the global eradication programme. Although OPV is a safe vaccine, on rare occasions adverse events may occur. Vaccine-associated paralytic poliomyelitis (VAPP) is the most important of these rare adverse events. Cases of VAPP are clinically indistinguishable from poliomyelitis caused by WPV, but can be distinguished by laboratory analysis. Sabin viruses can spread in populations where the coverage of OPV is low and they can acquire the neurovirulence and transmissibility characteristics of WPV. This may result in polio cases and outbreaks as circulating vaccine-derived poliovirus (cVDPV). These serious events become increasingly unacceptable as the number of paralytic cases due to circulating wild poliovirus declines, and when transmission of wild virus ends, the complete cessation of paralytic disease due to poliovirus will lead to the end of OPV usage.

Polio Vaccine Standardization

Written Standards

The WHO Guidelines for the safe production and quality control of inactivated poliomyelitis vaccine manufactured from wild polioviruses were developed in 2003 and revised in 2018. These revised WHO Guidelines provide information and guidance to vaccine manufacturers and relevant national authorities on the biosafety measures required for poliomyelitis vaccine production and quality control during the final poliovirus containment stage (Phase III) as defined in the WHO Global Action Plan to minimize poliovirus facility-associated risk after type-specific eradication of wild polioviruses ad sequential cessation of oral polio vaccine use (GAPIII). The previous version of these WHO Guidelines dealt with the safe production and quality control of IPV based specifically on wild-type strains. The revised Guidelines address the containment measures needed during the production and quality control of: 1) IPV produced from wild-type poliovirus strains; 2) IPV produced from the live attenuated vaccine (Sabin) strains used in the manufacture of OPV; and 3) OPV and IPV produced from novel safer strains developed by genetic manipulation.

Guidelines for safe production and quality control of poliomyelitis vaccines, Annex 4, TRS 1016. Replacement of Annex 2 of WHO Technical Report Series, No. 926.

Guidelines for the safe production and quality control of poliomyelitis vaccines, Annex 3, TRS 1028. Amendment to Annex 4 of WHO Technical Report Series, No. 1016

Inactivated Polio Vaccine (IPV)

The requirements for poliomyelitis vaccine (inactivated) were first formulated in 1959 and revised in 1965. Following several advances in technology in vaccine production, the requirements were further updated in 1981 and amended in 1985. At that time, the introduction of continuous cells for manufacture of poliomyelitis vaccine (inactivated) (IPV) was a novel development and when the control of products manufactured in continuous cells had been standardized, the requirements again updated in 2000 as Recommendations. Since then there have been several changes in vaccine production, including the use of seed viruses derived from Sabin strains, which made further revision of the Recommendations necessary. The WHO Expert Committee on Biological Standardization (ECBS) adopted Recommendations to Assure the Quality, Safety and Efficacy of Poliomyelitis Vaccines (Inactivated) at its 65th meeting in 2014. This guidance document outlines the recommendations to NRAs and manufacturers on the quality, nonclinical and clinical aspects of IPV in order to ensure the quality, safety and efficacy of the vaccines. The scope of the document encompasses IPV derived from: (a) the wild-type strains that have been used in the manufacture of IPV for many years; (b) the attenuated Sabin strains that have been used in the manufacture of oral poliomyelitis vaccine (OPV); and (c) new alternative poliovirus strains currently under development, including those derived by recombinant DNA technology.

Recommendations to assure the quality, safety and efficacy of poliomyelitis vaccines (inactivated), Annex 3, TRS 1024. Amendment to Annex 3 of WHO Technical Report Series, No. 993

Recommendations to assure the quality, safety and efficacy of poliomyelitis vaccines (inactivated), Annex 3, TRS 993. Replacement of Annex 2 of WHO Technical Report Series, No. 910

Oral Polio Vaccine (OPV)

Requirements for poliomyelitis vaccine (oral) were first formulated in 1962 and revised in 1966 and 1972 when an appendix detailing the production of OPV in human diploid cells was added. The Requirements were further updated 1982 following an accumulation of data particularly on the performance and evaluation of the monkey neurovirulence test and tests on the karyology of human diploid cells. The recommendations were updated in 1989 to take account of the general requirements for the characterization of continuous cell lines for the preparation of biologicals which were adopted in 1985 and after a WHO Study Group concluded that, in principle, such cell lines are acceptable as substrates for the production of biologicals. The requirements were revised in full in 1999 when new quality control tests were introduced for the vaccine including the test in TgPVR21 mice as an alternative to the monkey neurovirulence test for poliovirus type 3. An addendum was approved in 2000 to extend the use of this test to all three poliovirus serotypes. Since then, advances in scientific knowledge have been made, novel laboratory techniques have become available and new vaccine formulations are used. In addition, various tests are applicable to all three types of polioviruses, and their significance needs to be better explained and rationalized. Guidance on the nonclinical and clinical evaluation of new candidate OPVs are also required. The last fully revised WHO Recommendations to assure the quality, safety and efficacy of poliomyelitis vaccines (oral, live, attenuated) were adopted by the WHO ECBS at its meeting in October 2012 and published in WHO TRS No. 980, Annex 2. Since then, significant progress has been made towards global polio eradication, and important advances made in scientific knowledge, novel laboratory techniques, and the development of new non-pathogenic strains of polioviruses for use in quality control tests. Rationally designed and more genetically stable strains of Sabin 2 poliovirus were developed to minimize reversion of the vaccine strain to virulence and have been used to manufacture novel OPV2 (nOPV2). In addition, since the 2012 revision of the WHO Recommendations, new WHO guidance documents have also been issued including the WHO Global Action Plan to minimize poliovirus facility-associated risk after type-specific eradication of wild polioviruses and sequential cessation of oral polio vaccine use (GAPIII) was adopted in 2014 with a subsequently revised 4th edition (GAPIV) produced in 2022, the adoption of the revised WHO Guidelines for the safe production and quality control of poliomyelitis vaccines, and so on. WHO set up a drafting group and convened series of consultations on the revision of the 2012 Recommendations. The final revised WHO Recommendations to assure the quality, safety and efficacy of poliomyelitis vaccines (oral, live, attenuated) were adopted by the seventy-sixth meeting of the WHO ECBS, 24–28 October 2022.

Recommendations to assure the quality, safety and efficacy of poliomyelitis vaccines (oral, live, attenuated). Replacement of Annex 2 of WHO Technical Report Series, No. 980

SOP

• SOP: Mutant Analysis by PCR and Restriction Enzyme Cleavage (MAPREC) for Oral Poliomyelitis (Sabin) Vaccine Types 1, 2 or 3
• SOP: Neurovirulence Test of Types 1, 2 or 3 Live Attenuated Poliomyelitis Vaccines (Oral) in Monkeys
• SOP: Neurovirulence Test of Types 1, 2 or 3 Live Attenuated Poliomyelitis Vaccines (Oral) in Transgenic Mice susceptible to Poliovirus

Reference materials

WHO reference materials for poliomyelitis vaccines are available to qualified applicants. Please visit the website for individual vaccines and the catalogue of International reference Preparations.

International Reference Preparations catalogue

Poliomyelitis vaccines are prequalified for procurement by UN organization.

From March 2016 there is a new system for display of WHO prequalified vaccines

List of Prequalified Vaccines

WHO position paper on Poliomyelitis vaccination

Global Polio Eradication Initiative

SAGE Working Group on Polio