Poliomyelitis live

Poliomyelitis (live or oral) (Sabin type) Cell cultures infected with attenuated poliovirus of each of the three serotypes 1 Clarification 2 Blending of virus of three serotypes in stabilizing medium Infectivity titration of each of three virus serotypes Test for attenuation by Inoculation of spinal cords of monkeys and comparison of lesions with those produced by a reference 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. 

Poliomyelitis (inactivated)t (Salktype) Human diploid cell cultures infected with each of the three serotypes of poliovirus 1 Clarification 2 Inactivation with formalin 3 Concentration 4 Blending of virus of each serotype Induction of antibodies to polioviruses in chicks or guinea-pigs Inoculation of cell cultures and monkey spinal cords to exclude live virus... 

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. 

Two major advantages stem from the use of live vaccines. Firstly, the immunization mimics a natural infection such that only a single exposure is required to render an individual immune. Secondly, the exposure may be mediated through the natural route of infection (e.g. oral) thereby stimulating an immime response that is appropriate to a particular disease (e.g. secretory antibody as primary defence against poliomyelitis virus in the gut). 

Disadvantages associated with the use of live vaccines are also apparent. Live attenuated vaccines, administered through the natural route of infection, will be replicated in the patient and could be transmitted to others, ff attenuation is lost during this replicative process then irrfectiorrs rrtight result (see poliomyelitis, below). A second, major disadvantage of live vaccines is that the course of their action might be affected by the infeetion and immunological status of the patient. 

Polio is the only disease, at present, for which both hve and killed vaccines compete. Since the introduction of the killed vims (Salk) in 1956 and the live attenuated virus (Sabin) in 1962 there has been a remaikable decline in the incidence of poliomyelitis (Fig. 16.1). The inactivated polio vaccine (TPV) contains formalin-killed poliovirus of all three serotypes. On injection, the vaccine stimulates the production of antibodies of the IgM and IgG class which neutrahze the vims in the second stage of infection. A course of three injections at monthly intervals produces long-lasting immunity to all three poliovirus types. 

The first inactivated poliovirus vaccine was introduced in the 1950s in an injectable formulation, and replaced in the 1960s by a live oral poliovirus vaccine. The oral poliovirus vaccine not only elicits systemic immunogenicity but also a localized immune response in the intestinal tract. Unfortunately, the oral poliovirus vaccine has the risk of vaccine-associated paralytic poliomyelitis occurring in approximately 1 case of every 2.4 million doses distributed. The risk with the first dose of oral poliovirus vaccine is 1 case in 750,000 doses.11... 

Formaldehyde-killed Yersinia pestis Mixture of purified surface polysaccharide antigens obtained from differing serotypes of Streptococcus pneumoniae Live attenuated strains of poliomyelitis virus... 

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

Many of the more prominent vaccine preparations in current medical use consist of attenuated viral particles (Table 10.11). Mumps vaccine consists of live attenuated strains of Paramyxovirus parotitidis. In many world regions, it is used to routinely vaccinate children, often a part of a combined measles, mumps and rubella (MMR) vaccine. Several attenuated strains have been developed for use in vaccine preparations. The most commonly used is the Jeryl Linn strain of the mumps vaccine, 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%. 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. 

Poliomyelitis. Two vaccines are licensed for the control of poliomyelitis in tile United States. The live, attenuated oral polio virus (OPV) vaccine can be used for the immunization of normal children. The killed or inactivated vaccine is recommended for immunization of adults at increased risk of exposure to poliomyelitis and of lmmunodeficient patients and their household contacts. Both vaccines protect against the three serotypes of poliomyelitis that cause disease. 

Oral vaccines that are licensed for human administration are limited. Presently, there are few oral vaccines licensed for human use (Table 11.2), although many orally administered vaccine candidates are in development. Live attenuated oral polio (OPV) is the vaccine of choice for the prevention of poliomyelitis... 

Two types of trivalent poliovirus vaccines are currently licensed for distribution in the United States an enhanced inactivated vaccine (IPV) and a live attenuated, oral vaccine (OPV). IPV is the recommended vaccine for the primary series and booster dose for children in the United States, whereas OPV is recommended in areas of the world that have circulating pohovirus. IPV is given to children aged 2, 4, and 6 to 18 months and 4 to 6 years. Primary poliomyelitis immunization is recommended for all children and young adults up to age 18 years. Allergies to any component of IPV, including streptomycin, polymyxin B, and neomycin, are contraindications to vaccine use. 

Response to nonliving antigens (tetanus, typhoid, poliomyelitis) is diminished and giving one or two extra doses may be wise. Living vaccines are contraindicated in patients who are immunosuppressed by drug therapy or indeed by disease (AIDS, leukaemia, reticulosis) as there is a risk of serious generalised infection. 

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). 

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. 

In the view of the WHO, live vaccines should in general not be given to immunocompromised individuals, but in developing countries, the risk of poliomyelitis in non-immunized infants is high and the risk from these vaccines, even in the presence of symptomatic HIV infection, appears to be lower (47). 

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). 

No medical or therapeutic procedure comes without some risk to the patient. All possible steps are taken to ensure safety, quality and efficacy of vaccines and immunological products (Chapter 23). The risks associated with immunization procedures must be constantly reviewed and balanced against the risks of, and associated with, contracting the disease. In this respect, smallpox vaccination in the UK was abandoned in the mid-1970s as the risks associated with vaccination then exceeded the predicted number of deaths that would follow importation of the disease. Shortly after this, in May 1980, the World Health Assembly pronounced the world to be free of smallpox. Similarly, the incidence of paralytic poliomyelitis in the USA and UK in the late 1990s was low with the majority of cases being related to vaccine use. As the worldwide elimination of poliomyelitis approaches, there is much debate as to the value of the live (Sabin) vaccine outside of an endemic area. 

Faecal excretion of vaccine virus will occur and may last for up to 6 weeks post-treatment. Such released virus will spread to close contacts and infect/(re-)immunize them. Vaccine-associated poliomyelitis may occur through reversion of the attenuated strains to the virulent wild-type, particularly with types II and III and is estimated to occur once per 4 million doses. As the wild-type virus can be isolated in faeces, infection may occur in unimmunized contacts as well as vaccine recipients. Since the introduction of OPV, notifications of paralytic poliomyelitis in the UK have dropped spectacularly. However, from 1985 to 1995,19 of the 28 notified cases of paralytic poliomyelitis were associated with revertant vaccine strains (14 recipients, 5 contacts). As the risk of natural infections with poliomyelitis within developed countries has now diminished markedly, the greater risk resides with the live vaccine strains. Proposals are therefore now being considered that in the developed world OPV should be replaced with IPV. 

With the development of vaccines medicine gained the ability to control, eliminate, or even eradicate selected diseases. The classical vaccines consisting mostly of killed or live attenuated microbial agents or their isolated components have been highly successful. Smallpox has been eradicated, and viral diseases like measles, mumps, poliomyelitis, rubella and yellow fever rarely occur in developed countries. Similar success has been achieved with bacterial diseases such as diphteria, tetanus, tubercolosis and whooping cough, and equally successful were vaccines in veterinary medicine. However, many diseases remain for which no... 

The principles applied to smallpox may be generally applicable to other live attenuated vaccines (e.g. measles, mumps, rubella, poliomyelitis, BCG), but no studies seem to have been done to establish what is safe. It is generally accepted that patients taking immunosuppressants should not be given live vaccines. Problems with topical or inhaled steroids in normal dosages seem unlikely because the amounts absorbed are relatively small. However, this needs confirmation. The British National Formulary states that live vaccination should be postponed for at least 3 months after stopping high-dose corticosteroids. ... 

Polyomaviruses. The emergence of a few SV40 simian polyomavims-induced human cancers occurred after the ingestion of the first batch of the attenuated live poliomyelitis vims vaccines reviewed in [1908]. Some slowly replicating SV40 vims particles containing only one 72 bp enhancer remained much less detectable in... 

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