Lecture 6. Poliovirus Vaccination Flashcards

1
Q

What are the two vaccines for poliovirus?

A

Inactivated Poliovirus Vaccine (IPV)
Oral (Live attenuated) Poliovirus Vaccine (OPV)

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2
Q

Who developed IPV and OPV?

A

Developed by Salk and Sabin respectively

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3
Q

What is the inactivate poliovirus vaccine (IPV)?

A

Given by injection
Does not cause disease (if properly prepared - kills cells)
Used 1955-1961, 2000-present (US)

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4
Q

What is the oral (live attenuated) poliovirus vaccine (OPV)?

A

Given orally, easy to administer
Induced intestinal immunity
Mutant viruses derived from virulent strains
Usually reverts during intestinal replication
Used 1961-2000 (US)
In most of the globe, OPV is being used for eradication

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5
Q

What did the introduction of OPV cause?

A

Huge decrease in the number of polio cases

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6
Q

What part of the poliovirus infection does OPV target?

A

Replication in oropharynx and intestine
Limiting replication reduces the chances of disease forming

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7
Q

What part of the poliovirus infection does IPV target?

A

Poliovirus in the blood

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8
Q

Which polio vaccine was available first?

A

IPV

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9
Q

How does IPV prevent infection?

A

Formaldehyde-inactivation of neurovirulent virus (wild type poliovirus, wPV)

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10
Q

How many serotypes does IPV contain and why?

A

3 (vp1, vp2 and vp3) - protection against one stereotype doesn’t provide protection against other serotypes

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11
Q

What doesn’t IPV block?

A

Replication in gut, hence doesn’t block wPV transmission (does prevent disease due to wPV)

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12
Q

When was IPV reintroduced in the US and UK?

A

US: 2000
UK: 2006

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13
Q

In the UK what other vaccines are given at the same time as IPV?

A

Diptheria, pertussis, tetanus, Hib, HBV

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14
Q

What was the “Cutter incident” of 1955?

A

IPV from Cutter Laboratories used in ~200,000 children in West and Mid-West states
40,000 cases of disease; 200 paralysed, 10 died
Inadequately inactivated IPV batch (contained virulent virus)

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15
Q

What were the consequences from the “Cutter incident”?

A

Abandonment of first polio mass vaccination campaign
Replacement of IPV with OPV for US vaccinations
A ‘dangerous’ vaccine replaced by a more dangerous one

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16
Q

What does OPV prevent?

A

Replication in gut
Prevents transmission, of wPV
Develops antibodies in the mucosa
Binds to surface proteins preventing binding to the host

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17
Q

What did OPV cause in the late 1950s?

A

Low rate of vaccine assocaited poliomyelitis (VAPP)

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18
Q

Is OPV production the same for all types of poliovirus?

A

Yes

19
Q

What is the process in creating the OPV vaccine?

A

Starting with an isolate from a fatal case and subculturing the strain through multiple cell cultures (such as in vivo in monkeys or in vitro in monkey testicular/kidney cultures) and passaging many times until vaccine strain is achieved (through mutation and become non-virulent)

20
Q

How many types of OPV are there?

A

3
P1/Sabin, P2/Sabin, P3/Sabin

21
Q

What does VP1 aa 1106 mean?

A

Mutation in the amino acid sequence of VP1 at position 1106

22
Q

What does 5’-UTR nt 480 mean?

A

Mutation in the nucleotide at position 480 in the 5’-UTR (no change in amino acid sequence as part of the untranslated regions)

23
Q

What do mutations reduce the binding of onto the IRES?

A

Polypyrimidine tract binding protein to the IRES (point mutation is all that it takes to disrupt)

24
Q

When was smallpox declared to be eradicated?

A

1978 after an eradication program was launched in 1967

25
Q

What were the conditions that allowed smallpox to be eradicated?

A

Replication must occur only in one host
Vaccination must induce life-long immunity

26
Q

Why was it assumed that OPV usage could cease after eradication of polio was achieved?

A

No non-human host of poliovirus
Polio only affects humans, there is no animal reservoir
An effective, inexpensive vaccine exists
Immunity is life-long
There are no long-term carriers
The virus cannot survive for long outside the body

27
Q

Why would polio eradication prove difficult?

A

200:1 inapparent infection (asymptomatic but spread the disease)
Symptoms similar to other diseases
Vaccine reverts to virulence: disease in 1 in 10⁶ recipients
Poliovirus vaccine differs from smallpox in that it can revert to a wild-type virulent strain
In countries using OPV, the only source of poliovirus eventually is the vaccine

28
Q

What are the ongoing polio eradication issues?

A

Breaking chains of transmission in remaining hot-spots (geo-political issues; monovalent vaccines)
Funding for continuing vaccination efforts: Many poorer polio-free countries have relatively low vaccination coverage in population
Are there long-term vaccinated carriers?
The reversion of OPV strains is making eradication difficult

29
Q

What was the strategy for polio eradication in 1988?

A

Routine immunisation with trivalent OPV
Supplementary additional doses of OPV during National Immunisation Days
Mopping-up immunisation activities
Enhanced surveillance for all cases of acute flaccid (floppy) paralysis and wild poliovirus
Progressive declaration of areas as polio-free: requires three years without any locally transmitted cases
Target: global eradication by 2005

30
Q

In 2003 what were the remaining polio-endemic countries?

A

Egypt, Niger, Nigeria, Afghanistan, Pakistan, India

31
Q

How many cases of polio were there in 1999 and 2000?

A

1999: 7141
2000: 2971

32
Q

When were Egypt and Niger declared wild polio free?

A

Jan 2006

33
Q

When was India declared wild polio free?

A

2012

34
Q

In the UK since Feb 2022, where have Sabin-like type 2 poliovirus isolates been found and what could this cause?

A

Sabin-like type 2 poliovirus isolates have consistently been detected in sewage samples collected from London
New consistent detection of the virus these samples were classified as ‘circulating’ VDPV2
Samples collected had sufficient mutations to qualify as vaccine derived polio virus type 2 (VDPV2)
No human case associated with VDPV2 has been reported in the United Kingdom

35
Q

How do the attenuated mutations from OPV strains revert and become infectious again?

A

Sabin (OPV) strains replicate in the gut of immunocompetent individuals for a limited period of time
Poliovirus is excreted for periods of up to 30–60 days
During this time, attenuating mutations present in the vaccine strains revert rapidly and the virus becomes virulent
These reverted strains, vaccine-derivative poliovirus (VDPV) strains are excreted into the environment by vaccines

36
Q

What do vaccine-derivative polioviruses (VDPV) cause?

A

Vaccine-associated paralytic poliomyelitis (VAPP) in OPV recipients and their close contacts (unvaccinated)

37
Q

What is vaccine-associated paralytic poliomyelitis (VAPP) defined by the WHO as?

A

Poliomyelitis that occurs in a vaccine between 7 and 30 days after a dose or in a person in close contact with a vaccine between 7 and 60 days after the dose was received

38
Q

When were the first VDPP cases and what caused them?

A

First VDPP cases due vaccine-derived type 3 poliovirus in eastern Europe, early 1960s

39
Q

What can attenuated poliovirus mutate and become?

A

More virulent, thereby causing poliomyelitis more frequently, or to become more easily transmissible and thus can circulate to cause small outbreaks-circulating vaccine-derived poliovirus (cVDPV) strains

40
Q

What is the ease of reversion for the VDPV strains?

A

VDPV2 > VDPV3 > > VDPV1

41
Q

How many million births have VAPP?

A

1/1,000,000

42
Q

What are circulating vaccine-derived polioviruses (cVDVP) now more significant than?

A

wPV

43
Q

What must complete eradication of poliovirus address?

A

cVDPV as well as wPV