Poliomyelitis vaccine

Cell cultures provide infeeted fluids that eontain little debris and can generally be satisfactorily clarified by filtration. Beeause most viral vaccines made fiom cell cultures consist of live attenuated vims, there is no inaetivation stage in their manufacture. There are, however, two important exeeptions inaetivated poliomyelitis vims vaccine is inactivated with dilute formalin or /3-propiolaotone and rabies vaccine is inactivated with /3-propiolactone. The preparation of these inaetivated vaccines also involves a concentration stage, by adsorption and elution of the vims in the case of poliomyelitis vaccine and by ultrafiltration in the case of rabies vaceine. When processing is complete the bulk materials may be stored until needed for blending into final vaccine. Because of the lability of many vimses, however, it is necessary to store most purified materials at temperatures of-70°C. 

An example fiom virus vaeeine manufaeture is the titration, prior to inactivation, of the infectivity of the pools of live poliovims used to make inactivated poliomyelitis vaccine. Adequate infectivity of the virus from the tissue cultures is an indicator of the adequate virus content of the starting material and, sinee infectivity is destroyed in the inactivation process, there is no possibility of performing such an estimation after formolization. 

Viral vaccines present problems of safety testing far more complex than those experienced with bacterial vaccines. With killed viral vaccines the potential hazards are those due to incomplete virus inactivation and the consequent presence of residual live virus in the preparation. The tests used to detect such live virus consist of the inoculation of susceptible tissue cultures and of susceptible animals. The cultures are examined for cytopathic effects and the animals for symptoms of disease and histological evidence of infection at autopsy. This test is of particular importance in inactivated poliomyelitis vaccine, the vaccine being injected intraspinally into monkeys. At autopsy, sections of brain and spinal cord are examined microscopically for the histological lesions indicative of proliferating poliovirus. 

With attenuated viral vaccines the potential hazards are those associated with reversion of the virus during production to a degree of virulence capable of causing disease in vaccinees. To a large extent this possibility is controlled by very careful selection of a stable seed but, especially with live attenuated poliomyelitis vaccine, it is usual to compare the neurovirulence of the vaccine with that of a vaccine known to be safe in field use. The technique involves the intraspinal inoculation of monkeys with a reference vaccine and with the test vaccine and a comparison ofthe neurological lesions and symptoms, if any, that are caused. If the vaccine causes abnormalities in excess of those caused by the reference it fails the test. 

Poliomyelitis vaccine (Salk Inactivated poliomyelitis virus vaccine parenteral)... 

Several attenuated strains have been developed for use in vaccine preparations. The most commonly used is the Jeryl Linn strain, which is propagated in chick embryo cell culture. This vaccine has been administered to well over 50 million people worldwide and, typically, results in seroconversion rates of over 97 per cent. The Sabin (oral poliomyelitis) vaccine consists of an aqueous suspension of poliomyelitis virus, usually grown in cultures of monkey kidney tissue. It contains approximately 1 million particles of poliomyelitis strains 1,2 or 3 or a combination of all three strains. 

Poling kettle, in tin refining, 24 788 Polioencephalomalacia, 10 867 Poliomyelitis vaccine, 5 345t 25 488 Polio virus, 22 10, 11 Polished metals, and object mode perceptions, 7 306t Pohshes, colloids, 7 273t Pohshing, of staple-fiber non woven fabrics, 27 515... 

Poliomyelitis vaccine Live attenutated strains of poliomyelitis Active immunization against... 

Poliomyelitis vaccine (Salk vaccine parenteral) Inactivated poliomyelitis virus Active immunization against polio... 

Salk, I, U. Krech, and 1. Younger, Formaldehyde and safety testing of experimental poliomyelitis vaccines. Am 1 Publ Health, 1954. 44 563-70. 

Pineau A, Durand C, Guillard O, et al. 1992. Role of aluminum in skin reactions after diphtheria-tetanus-pertussis-poliomyelitis vaccination An experimental study in rabbits. Toxicology 73 117-125. 

The norms for medicinal production are particularly stringent. Biological products are composed of complex molecules, produced by cell lines with a relatively recent history, and difficult to characterize. Tests performed only on the final product do not guarantee consistency of production. The purification procedures should be planned and validated for the removal of potential contaminants from diverse sources cells, culture media, equipment, and reagents used in the purification or even degradation products derived from the protein itself. There are examples of products with unexpected risks that have caused serious problems such as blood contamination by HIV-1 virus between 1980 and 1985 (Bloom, 1984) or the presence of residual infectious viruses in the poliomyelitis vaccine due to inefficient inactivation (Lubiniecki et al., 1990). 

WFIO (1990), Expert Committee on Biological Standardization, Requirements for poliomyelitis vaccine (oral), Tests for bovine viruses in serum, Geneva, Appendix 1 p. 66 [Technical Report Series no. 800]. 

An example of the role(s) that primate research has played is in the development of the poliomyelitis vaccines. Although many studies on poliomyelitis in humans were conducted in the late nineteenth century, the cause of the disease remained unknown until scientists succeeded in transmitting the virus to monkeys in 1908. There followed many years of research with primates until scientists were able, in the early 1950s, to grow the virus in human cell cultures and development of a vaccine became possible. At that point in time, in order to ensure the safety and effectiveness of the vaccines, tests were conducted with monkeys. Furthermore, in order to produce the vaccines in pure form in great quantities, it was necessary to use kidney tissue taken from monkeys. Today, an alternative to the use of monkey kidneys has been developed for the production of the vaccine. 

Guillain-Barre syndrome has been reported after immunization with several different vaccines, including Hib conjugate vaccine (13,14). One patient had also received DTP and oral poliomyelitis vaccine. 

When recombinant hepatitis B vaccine was given together with DTP vaccine and oral poliomyelitis vaccine, there was no evidence of increased reactogenicity after simultaneous administration compared with hepatitis B vaccine alone (86). 

In 40 children born to HBsAg-positive mothers who had received second and third doses of hepatitis B vaccine simultaneously with DTP vaccine and inactivated poliomyelitis vaccine, immunogenicity and reactogenicity were comparable with non-simultaneous administration of the different vaccines (87). 

Torres JM, Bruguera M, Vidal J, Artigas N. Immune response, efficacy and reactogenicity of hepatitis B vaccine administered simultaneously with DTP and poliomyelitis vaccine. Gastroenterol Hepatol 1993 16 470-3. 

Immunocompromise is a contraindication to the use of live virus vaccines, such as measles, mumps, rubella, and oral poliomyelitis vaccine. It is recommended that rubella or MMR vaccine should not be given to persons who are immunosuppressed because of AIDS or other clinical manifestations of HIV infection. The vaccine can be given to asymptomatic infected people (139). 

A follow-up study has been carried out in 105 children with collapse (a hypotonic-hyporesponsive episode or a shock-like syndrome) after their first immunization with DTwP -I- IPV vaccine (11). Information about subsequent immunizations, health, and development in 101 of the children was supplied by child health-care units. The parents of one child refused further immunization, 16 children completed their schedule with the combination diphtheria -I- tetanus -I- poliomyelitis vaccine (DT-IPV), and the other 84 children received further pertussis vaccine (DTP-IPV), totalling 236 doses 74 children received the complete series of three additional doses. None of the children had recurrent collapse, and other adverse events were only minor. About half were given paracetamol prophylactically for the first subsequent dose most of them did not take it for further doses. The authors suggested that it is unnecessary to withhold further doses of pertussis vaccine in a child with collapse after a previons dose. It has been suggested that the threat of natural pertussis in non-immunized children should be taken much more into account than the fear of developing a collapse reaction (12). In another study (13) in the USA, one of the 14 children not completely immunized becanse of a hypotonic-hyporesponsive episode after a previons dose later developed natural pertussis, which lasted for 3 months and was transmitted to both her parents. 

There are two types of pohomyelitis vaccines available. One is prepared from pohoviruses that as a rule have been inactivated by formaldehyde. Inactivated poliomyelitis vaccine (IPV) is given parenterally. The second group of polio vaccines comprises attenuated strains of live polioviruses (oral poliomyelitis vaccine, OPV), which are given orally these live vaccines are the most widely used. 

Cockburn WC. The work of the WHO Consultative Group on Poliomyelitis Vaccines. Bull World Health Organ... 

Ozawa H, Noma S, Yoshida Y, Sekine H, Hashimoto T. Acute disseminated encephalomyelitis associated with poliomyelitis vaccine. Pediatr Neurol 2000 23(2) 177-9. 

Burkhard C, Choi M, Wilhelm H. Optikusneuritis als Komplikaton einer Tetanus-Diphtherie-Poliomyelitis-Schutzimpfung ein Fallbericht. [Optic neuritis as a complication in preventive tetanus-diphtheria-poliomyelitis vaccination a case report.] Klin Monatsbl Augenheilkd 2001 218(l) 51-4. 

In the early days of vaccine development the majority of untoward effects after immunization were associated with faulty production, and the control of biological products as they exist today has been developed largely as a result of major accidents. For example, the Cutter incident in the USA in 1955, in which a batch of inactivated poliomyelitis vaccine containing live poliovirus was inadvertently released, had devastating consequences. The World Health Organization (WHO) subsequently took over the responsibility for international biological standardization. Currently, more than 50 WHO requirements for the manufacture and control of biological substances have been adopted and updated. As a result of the incorporation of WHO requirements, and their strict observance by manufacturers and control authorities, accidents due to faulty production of vaccines have become rare (SEDA-13, 271). 

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