Lecture 6. Poliovirus Vaccination Flashcards by Ben Hallam

What are the two vaccines for poliovirus?

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

How well did you know this?

Not at all

Perfectly

Who developed IPV and OPV?

Developed by Salk and Sabin respectively

How well did you know this?

Not at all

Perfectly

What is the inactivate poliovirus vaccine (IPV)?

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

How well did you know this?

Not at all

Perfectly

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

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

How well did you know this?

Not at all

Perfectly

What did the introduction of OPV cause?

Huge decrease in the number of polio cases

How well did you know this?

Not at all

Perfectly

What part of the poliovirus infection does OPV target?

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

How well did you know this?

Not at all

Perfectly

What part of the poliovirus infection does IPV target?

Poliovirus in the blood

How well did you know this?

Not at all

Perfectly

Which polio vaccine was available first?

IPV

How well did you know this?

Not at all

Perfectly

How does IPV prevent infection?

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

How well did you know this?

Not at all

Perfectly

How many serotypes does IPV contain and why?

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

How well did you know this?

Not at all

Perfectly

What doesn’t IPV block?

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

How well did you know this?

Not at all

Perfectly

When was IPV reintroduced in the US and UK?

US: 2000
UK: 2006

How well did you know this?

Not at all

Perfectly

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

Diptheria, pertussis, tetanus, Hib, HBV

How well did you know this?

Not at all

Perfectly

What was the “Cutter incident” of 1955?

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)

How well did you know this?

Not at all

Perfectly

What were the consequences from the “Cutter incident”?

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

How well did you know this?

Not at all

Perfectly

What does OPV prevent?

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

How well did you know this?

Not at all

Perfectly

What did OPV cause in the late 1950s?

Low rate of vaccine assocaited poliomyelitis (VAPP)

How well did you know this?

Not at all

Perfectly

Is OPV production the same for all types of poliovirus?

Yes

What is the process in creating the OPV vaccine?

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)

How many types of OPV are there?

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

What does VP1 aa 1106 mean?

Mutation in the amino acid sequence of VP1 at position 1106

What does 5’-UTR nt 480 mean?

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

What do mutations reduce the binding of onto the IRES?

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

When was smallpox declared to be eradicated?

1978 after an eradication program was launched in 1967

What were the conditions that allowed smallpox to be eradicated?

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

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

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

Why would polio eradication prove difficult?

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

What are the ongoing polio eradication issues?

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

What was the strategy for polio eradication in 1988?

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

In 2003 what were the remaining polio-endemic countries?

Egypt, Niger, Nigeria, Afghanistan, Pakistan, India

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

1999: 7141 2000: 2971

When were Egypt and Niger declared wild polio free?

Jan 2006

When was India declared wild polio free?

2012

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

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

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

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

What do vaccine-derivative polioviruses (VDPV) cause?

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

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

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

When were the first VDPP cases and what caused them?

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

What can attenuated poliovirus mutate and become?

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

What is the ease of reversion for the VDPV strains?

VDPV2 > VDPV3 > > VDPV1

How many million births have VAPP?

1/1,000,000

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

wPV

What must complete eradication of poliovirus address?

cVDPV as well as wPV