1/20/2017

Toward a Virus-Free Polio Vaccine

Researchers are developing polio vaccines based on the viral capsid alone. When produced in recombinant systems, these could eliminate the need to propagate live poliovirus for vaccine production. 
By  | January 19, 2017

Polio is nearly eradicated. But vaccine campaigns will continue in case, for example, some remaining infections go undetected. With the current technology, the need to continue vaccinations poses a challenge to a poliovirus-free world because “the only way you can make [vaccines] at the moment is using a live virus,” virologist Andrew Macadam at the U.K.’s National Institute for Biological Standards and Control, told The Scientist. The oral polio vaccine (OPV) contains live, attenuated virus; the inactivated polio vaccine (IPV) is made by growing, then killing, virulent virus. Both of these vaccines could cause outbreaks, through reversion of OPV to a virulent form or through leakage of live virus from an IPV production plant, Macadam explained.
To circumvent these problems, Macadam and colleagues are working to develop new vaccines that contain no virus at all. These consist of empty viral capsids, the viruses’ protein coats, called virus-like particles (VLPs). In a study published today (January 19) in PLOS Pathogens, the team reported having created capsid-based vaccines that are stable and, in rodent experiments, worked as well as IPVs in protecting against polio.
The study “opens up the possibility of not having to use virus to produce a virus-like particle which is noninfectious” said Olen Kew, the national poliovirus containment coordinator at the US Centers for Disease Control and Prevention, who was not involved in the research. “The facilities which handle by far the largest amounts of poliovirus are the vaccine producers,” Kew told The Scientist, “so if you can produce a vaccine without handling any virus at all, then that risk is eliminated.”

See “Toward Eliminating Poliovirus—In the Lab

VLPs, which are already used in hepatitis B and human papilloma virus (HPV) vaccines, represent a potential solution. However, previous research indicated that poliovirus capsids were too unstable and temperature-sensitive to work as vaccines.
Using a combination of selection experiments and previous knowledge of stabilizing mutations, Macadam’s team identified mutations that render the viral capsids stable at higher temperatures. They then introduced these mutations into the poliovirus strains currently used to make IPVs, grew the viruses in cultured cells, and purified away the empty capsids. In addition to infectious particles, polioviruses produce empty shells during their life cycles.
To test efficacy, the team vaccinated mice transgenic for the human poliovirus receptor with VLPs they had created, then challenged the rodents with poliovirus. The mice vaccinated with VLPs had higher levels of neutralizing antibodies (which kill the virus) than those vaccinated with IPV, and all of the VLP-vaccinated animals survived the challenge.
Macadam led this study in collaboration with a multi-institutional consortium, funded by the World Health Organization (WHO), to develop VLPs. While the VLPs used in these experiments were produced using live poliovirus, Macadam’s collaborators are working to produce VLPs in recombinant systems, which would remove live poliovirus from the production process altogether. “There’s been very good progress already. We have VLPs that have been made in mammalian systems and in plant systems and have made some very good progress in the insect and yeast cells,” said Macadam.
The WHO’s Roland Sutter said he believes that VLPs could replace current polio vaccines, but there’s much work to be done. If successful, these could “make the world a much safer place,” he said.
H. Fox et al., “Genetically thermo-stabilised, immunogenic poliovirus empty capsids; a strategy for nonreplicating vaccines,” PLOS Pathogensdoi:10.1371/journal.ppat.1006117, 2017.
Post Polio Litaff, Association A.C _APPLAC Mexico

The Polio Crusade

THE POLIO CRUSADE IN AMERICAN EXPERIENCE A GOOD VIDEO THE STORY OF THE POLIO CRUSADE pays tribute to a time when Americans banded together to conquer a terrible disease. The medical breakthrough saved countless lives and had a pervasive impact on American philanthropy that ... Continue reading..http://www.pbs.org/wgbh/americanexperience/polio/

Erradicación de La poliomielitis

Polio Tricisilla Adaptada

March Of Dimes Polio History

Dr. Bruno

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A 41-year-old man developed an acute illness at the age of 9 months during which, following a viral illness with headache, he developed severe weakness and wasting of the limbs of the left side. After several months he began to recover, such that he was able to walk at the age of 2 years and later was able to run, although he was never very good at sports. He had stable function until the age of 18 when he began to notice greater than usual difficulty lifting heavy objects. By the age of 25 he was noticing progressive difficulty walking due to weakness of both legs, and he noticed that the right calf had become larger. The symptoms became more noticeable over the course of the next 10 years and ultimately both upper as well as both lower limbs had become noticeably weaker.

On examination there was wasting of the muscles of upper and lower limbs on the left, and massively hypertrophied gastrocnemius, soleus and tensor fascia late on the right. The calf circumference on the right exceeded that on the left by 10 cm (figure1). The right shoulder girdle, triceps, thenar eminence and small muscles of the hand were wasted and there was winging of both scapulae. The right quadriceps was also wasted. The wasted muscles were also weak but the hypertrophied right ankle plantar flexors had normal power. The tendon reflexes were absent in the lower limbs and present in the upper limbs, although the right triceps was reduced. The remainder of the examination was normal.

Figure 1

The patient's legs, showing massive enlargement of the right calf and wasting on the left

Questions

1
What is that nature of the acute illness in infancy?
2
What is the nature of the subsequent deterioration?
3
What investigations should be performed?
4
What is the differential diagnosis of the cause of the progressive calf hypertrophy?

Answers

QUESTION 1

An acute paralytic illness which follows symptoms of a viral infection with or without signs of meningitis is typical of poliomyelitis. Usually caused by one of the three polio viruses, it may also occur following vaccination and following infections with other enteroviruses.1 Other disorders which would cause a similar syndrome but with upper motor neurone signs would include acute vascular lesions, meningoencephalitis and acute disseminated encephalomyelitis.

QUESTION 2

A progressive functional deterioration many years after paralytic poliomyelitis is well known, although its pathogenesis is not fully understood.2 It is a diagnosis of exclusion; a careful search for alternative causes, for example, orthopaedic deformities such as osteoarthritis or worsening scoliosis, superimposed neurological disorders such as entrapment neuropathies or coincidental muscle disease or neuropathy, and general medical causes such as respiratory complications and endocrinopathies.3

QUESTION 3

Investigations revealed normal blood count and erythrocyte sedimentation rate and normal biochemistry apart from a raised creatine kinase at 330 IU/l (normal range 60–120 IU/l), which is commonly seen in cases of ongoing denervation. Electromyography showed evidence of denervation in the right APB and FDI with polyphasic motor units and complex repetitive discharges, no spontaneous activity in the left calf and large polyphasic units in the right calf consistent with chronic partial denervation. Motor and sensory conduction velocities were normal. A lumbar myelogram was normal. Magnetic resonance imaging (MRI) scan of the calves is shown in figure2.

Figure 2

Axial T1 weighted MRI scan (TR 588 ms, TE 15 ms) of the calves, showing gross muscle atrophy and replacement by adipose tissue on the left, and hypertrophy of the muscles on the right, with only minor adipose tissue deposition

QUESTION 4

The differential diagnosis of the progressive calf hypertrophy is given in the box.

Causes of calf muscle hypertrophy

Chronic partial denervation

  • radiculopathy

  • peripheral neuropathy

  • hereditary motor and sensory neuropathy

  • spinal muscular atrophy

  • following paralytic poliomyelitis

    Neuromyotonia and myokymia

  • Isaac's syndrome

  • generalised myokymia

  • neurotonia

  • continuous muscle fibre activity due to: chronic inflammatory demyelinating polyradiculopathy, Guillain Barre syndrome, myasthenia gravis, thymoma, thyrotoxicosis, thyroiditis

    Muscular dystrophies

    Myositis

    Infiltration

  • tumours

  • amyloidosis

  • cysticercosis

    Link here