Poliovirus and Vaccination in the UK

Vaccination & Antiviral Drugs (MSOP-1004)

• Vaccination is a disease prevention strategy, often more effective than cure, particularly for infectious diseases where effective drugs are unavailable.
• Prophylaxis is a strategy to preserve health and prevent disease spread. Strategies include improvements in nutrition, sanitation, hygiene, and public health.
• Vaccination is a major disease control approach.

Introduction to Vaccination

• Prevention is better than cure in disease treatment.
• Prophylaxis strategies aim to preserve health and prevent disease spread.
• Vaccination (administration of a vaccine) is a key disease control approach.

Introduction to Vaccination

• A vaccine is a preparation designed to elicit immunity (resistance) to a disease.
• Vaccines can be prophylactic (prevent future infections) or therapeutic (treat existing infections like cancer or rabies).
• Most vaccines are prophylactic and aim to cause less disease than natural infection.

History of Vaccination

• Ancient Greeks observed that smallpox survivors were rarely reinfected.
• Chinese doctors practiced variolation (exposing healthy people to smallpox matter) over a thousand years ago.
• Variolation reduced smallpox mortality from approximately 30% to 1%.

History of Vaccination

• Variolation reached Turkey by 1700. In 1718, Lady Mary Wortley Montagu inoculated her son.
• On returning to England, she promoted variolation trials, including among prisoners on death row.
• All prisoners survived.

Jenner & Vaccination

• Edward Jenner, an English country doctor, observed that milkmaids rarely contracted smallpox, suggesting a connection to cowpox.
• Jenner hypothesized that cowpox exposure conferred protection against smallpox.
• In 1796, Jenner inoculated a boy with cowpox fluid and later challenged him with smallpox material; the boy remained healthy.

Jenner & Vaccination

• Jenner's findings were published by the Royal Society in 1798.
• Smallpox vaccination was introduced in 1840 (vacca = Latin for cow) and was free.
• Smallpox vaccination became compulsory in the UK in 1853

Smallpox

• Smallpox is caused by a poxvirus (family Orthopoxviridae, genus Variola, DNA genome).
• Host range is human though poxviruses infect other vertebrates too.
• Smallpox entry is through inhalation, ingestion, or direct contact with body fluids (saliva, pus).
• Target cells include skin epithelium and mouth mucosa, plus the blood.

Smallpox

• Symptoms begin about 12 days after infection, typically resembling the flu (fever, intestinal problems, vomiting).
• Smallpox causes pimples that progress into larger macules spreading across the body; fluid loss and/or opportunistic infections often lead to fatalities, with a fatality rate up to 40%.
• Survivors are often scarred with pockmarks; some exhibit hemorrhagic smallpox (skin, eyes, organs), leading to high mortality.

Smallpox Vaccination

• Smallpox killed millions in the 20th century.
• The World Health Organization launched a worldwide smallpox eradication program starting in 1967, a tremendous global effort.
• Vaccination employed a related orthopoxvirus, vaccinia virus, isolated from animal tissue and freeze-dried for storage.
• Vaccination is through a bifurcated needle piercing the skin.
• Vaccine confers immunity for approximately 10 years.

Smallpox Eradication

• WHO's strategy focused on endemic areas via surveillance and ring vaccination (isolating susceptible individuals near affected areas)
• This strategy dramatically reduced cases, with the final natural case in Somalia in 1977 – the first human disease to be eradicated!

Live & Dead Vaccines

• Live Vaccines: Use attenuated (weakened) microorganisms to stimulate immunity. Smallpox was primarily treated with a live vaccine.
• Dead Vaccines: Use inactivated pathogens, subcellular components, or surface proteins. Less commonly used than live vaccines and primarily used where safe live vaccines are not available.

Live & Dead Vaccines

• Vaccination is artificial immunity induction or immunisation using an immunogen to prime the immune system, elicit immune sensitisation and produce memory in B and T cells (leading to immunity via antibody and cell-mediated responses).
• Short-term protection may be conferred by temporary increases in antibodies, but maintaining memory is critical for long-term immunity.

Vaccines/Boosters

• Children receive vaccines to boost their developing immune systems before exposure to serious pathogens.
• Vaccines are often given multiple times to achieve peak immunity (i.e., booster shots) at intervals, especially for diseases wherein immunity declines over time (e.g., tetanus).
• Natural infections can also act as boosters.

Vaccines/Boosters

• Vaccine aims can range from individual protection to transmission blocking or eradication.
• Vaccines must be effective, safe, stable, and cost-effective, causing less illness than the infection they are intended to prevent.

Smallpox Vaccine

• Smallpox vaccines were highly effective due to the absence of asymptomatic carriers; outbreaks were thus easily identified and vaccinated.
• The vaccinia virus vaccine was generally safe, causing only mild infections (fever, rash), but some risk in individuals with skin conditions or compromised immune systems.

Smallpox Vaccine (continued)

• Smallpox vaccines were stable due to freeze-drying, enabling transport and storage even in warm environments.
• Cost for mass production was modest.
• Other costs included transport, storage, training, staff administration, education, and advertising.

Immunity

• Active immunity develops from exposure to immunogens (antigens). This can be natural or artificial (vaccines).
• Passive immunity results from receiving antibodies from another source, such as maternal antibodies across the placenta or in breast milk.

Immunity

• Passive immunity can also involve transfused human sera (for example for rabies prophylaxis), requiring prior antibody susceptibility to pathogens. Active immunity is not related to previous exposure.

Rabies

• Rabies vaccines are given to tourists visiting endemic areas.
• A passive immunoglobulin vaccine is critical for people bitten by rabies-infected animals as the complication rate is very high (virtually 100% fatal without intervention).

Immunity

• Herd immunity occurs when enough within a population have immunity, thus decreasing the number of susceptible individuals and slowing/stopping disease transmission.
• Reduced vaccine uptake can lead to increased disease risk in susceptible individuals.

Polio

• Polio is a human disease (RNA virus, family Picornoviridae, genus Enterovirus).
• Poliovirus has been known for millennia. Detailed medical descriptions appeared in prehistory.
• Symptoms range from subclinical or abortively mild polio infections (symptoms similar to the flu) to severe paralysis in a smaller fraction of cases where immunity may be immature, leading to serious complications.

Polio (continued)

• Polio often infects humans via fecal-oral contact; Poliovirus is resistant to stomach acid.
• Target cells include epithelium of throat and gut; the virus can enter the lymphatic system, blood, then neurons.
• Paralysis is a significant symptom; paralysis is often temporary if damage is not extensive, while in severe cases paralysis of breathing muscles can lead to death.

Polio Immunisation

• Salk developed the first effective polio vaccine (inactivated) in 1952 in the USA.
• The Salk vaccine used formalin to inactivate all three serotypes.
• The vaccine was licensed in 1955, and mass immunization campaigns significantly reduced polio cases due to the vaccine response.

Polio Immunisation (continued)

• However, some polio cases still occurred after Salk vaccination, due to incomplete inactivation of the virus. This issue was later resolved through effective inactivation processes
• Two initial intramuscular injections one month apart, with subsequent boosters, are widely administered.
• The vaccine stimulates lymphocyte production.

Salk's Polio Vaccine (IPV)

• Licensed in 1955 by the FDA.
• Provided 70% protection against poliovirus infection.

'Live' Polio Vaccine

• Albert Sabin developed a live attenuated polio vaccine in 1957.
• The vaccine contained attenuated (weakened) versions of all three serotypes.
• Attenuation was achieved through serial passage in non-human cell culture.

'Live' Oral Polio Vaccine (continued)

• Administered orally, usually multiple times during infancy, at intervals, to allow earlier infection symptoms to subside.
• Provides effective lifelong immunity in most cases.
• Not used for immunocompromised individuals.

Vaccination History: Polio

• The live oral polio vaccine, commonly used in some countries (besides the USA), occasionally experienced cases of "reversion to virulence" after passing through the gut, in a small number of cases (i.e., 1 in a million).
• Such reversion could lead to further transmission.

Poliovirus Antivirals

• There are no commonly used poliovirus antiviral agents, although several drugs are in various stages of development or clinical trial phases.
• The most advanced is V-073 (pocapivir), an antiviral inhibiting capsid uncoating.
• Another drug is V-7404 (virus-specific protease inhibitor). Both drugs are used concurrently.

Treatment of Polio

• Both live and inactive polio vaccines stimulate antibody production.
• The last case of polio in the Americas was in 1991.
• Polio remains endemic in specific countries (Nigeria, India, Pakistan, Afghanistan).
• Polio is one of few diseases where both live and dead vaccines compete in their respective usage.

Polio Immunisation (continued)

• In the UK, a new inactivated combination vaccine is now used.
• The WHO has embarked on a global eradication campaign. Governments, the WHO, and organisations like the Bill and Melinda Gates Foundation are involved in global initiatives to eradicate polio.

Polio eradication

• Global eradication initiatives lead to the eradication of wild poliovirus type 2 in 1999.
• Global initiatives, and mass vaccination campaigns, led to the eradication of wild poliovirus type 3.

Literature and Websites

• Relevant textbooks (Korsman, Schors, Denyer et al., et al.) and websites (WHO, etc.) are cited.

This quiz explores key aspects of polio vaccination, specifically focusing on coverage issues in the UK, vaccine delivery methods, and the global fight against poliovirus. Test your knowledge on polio vaccine administration, challenges in antiviral development, and historic trends related to polio cases in Europe.