Global Polio

Eradication Initiative
POLIO VACCINES
Facts about OPV

Dr Benjamin Nkowane
WHO/HQ

STOP TEAM 37 Training

Atlanta, May 2011

PART 1
POLIO VACCINES

Polio Eradication

Milestones
Landsteiner

and Popper: 1908 viral cause

In 1929, Drinker constructed iron lung
Burnet and MacNamara more than one
serotype of poliovirus in 1931
Enders, Weller and Robbins reported in
1949 that poliovirus could be grown in
non-nervous, human embryonic tissue
In 1951, Committee on Typing reported 3
serotypes of poliovirus (types 1, 2, and 3)
Polio Eradication

Poliovirus I
Genus:

Enterovirus,
Family: Picornaviridae
Non-enveloped
Genome: Single-stranded RNA of ~
7,500 nucleotides
Three major antigenic sites (surface
proteins VP1-3)
Three serotypes (1, 2, and 3)
Polio Eradication

Poliovirus II
Rapidly

inactivated by heat,
desiccation, formaldehyde, chlorine,
ultraviolet light
Requires specific receptor to enter
cells (tissue tropisms)
Cell entry to release of virions
following cell lysis and death ~ 4-5
hours
Polio Eradication

1950s Miracle:
Salk & Sabin
Vaccines

Polio Eradication

Vaccines
Inactivated

poliovirus vaccine (IPV)

licensed in 1955 (Salk)
Monovalent oral poliovirus vaccines
(OPV) starting in 1961 (Sabin)
Trivalent OPV since 1963 (Sabin)
Monovalent MOPV re-introduced
Bivalent OPV introduced in 2009
Polio Eradication

Polio Eradication

OPV and IPV Schedules

WHO/EPI

schedule requires 4 doses of

OPV at birth, 6, 10, 14 weeks
Some countries use 2, 4, 6 month OPV
or IPV schedule with an additional dose
at 18 months
OPV objective to achieve
seroconversion
IPV requires priming and booster doses
Polio Eradication

Adverse Events
OPV
Vaccine-associated paralytic

poliomyelitis (VAPP)
Vaccine recipients and contacts
1 VAPP per 700,000 first-dose
vaccine recipients
Immune deficient persons at
highest risk
Vaccine derived polio viruses
IPV
No systemic adverse events
Polio Eradication

Cases of Paralytic Poliomyelitis (Total

and Vaccine-Associated Cases),
United States, 1964-1992
120
100
80
Number of
60
Cases
40
20
0

VAPP
Total

OPV Immunogenicity
Industrialized countries
Seroconversion after 3 doses

97% to type 1,
100% to type 2
100% to type 3

Mucosal immunity requires at

least 2 OPV doses

Polio Eradication

OPV Immunogenicity
Developing countries
Seroconversion (median) after 3

doses
73% to type 1
90% to type 2
70% to type 3
10-15 doses needed >90% for
types 1 and 3
Mucosal immunity relatively
short-lived (months to years),
requires frequent boosters
Polio Eradication

Advantages &
Disadvantages
Advantages
OPV

Ease of administration
Price
Mucosal immunity
Secondary spread

Disadvantages
OPV

IPV

No adverse events
No VAPP

Polio Eradication

VAPP
Prolonged replication
in immune deficient
persons
Risk of circulation
after stopping OPV

IPV

Less mucosal
immunity
Injection required
Price

Poliovirus Antibody Seroprevalence Among

Unvaccinated Inner-City Preschool Children,
Detroit and Houston, 1990-1991
Detroit
70
60
50
40
Percent
30
20
10
0

Houston

64

43
34
17

21
10

P1

P2

12-23m

Polio Eradication

P3

24-35m

70
60
50
40
Percent
30
20
10
0

55
36
27

24
15

P1

12-23m

P2

24-35m

P3

Effect of Mass OPV Campaign outside of Study

District on Sero conversion to Poliovirus types 1,
2, and 3 between Birth and 10 Weeks, Oman*
Percent
100
90
80
70
60
50
40
30
20
10
0

1 IPV non-exposed
1 IPV exposed

Type 1

Type 2

Type 3

Polio
Eradication
*J
Infect
Dis 175(Suppl 1):S215-27

PART 2
Monovalent OPV

Information
brochure 1962

-mOPV: a retired vaccine that was recommissioned

-Extensive record of efficacy & safety from the
1960s (USA, USSR, Europe)
-Selective use in 1970s & 1980s; and
campaign use in Gaza Strip
-Replaced by tOPV in mid 1960s primarily for
programmatic reasons

Advisory Committee on Polio Eradication

(ACPE), 21-22 Sep 2004
ACPE reviewed options reviewed for
ACPE
deliberations
on mOPV1
influenced
by: 1)
maximising
immunity
for each
SIAs contact:
type
Recommendations:
2 eradicated globally; 2) type 3 circulation
All polio infected countries should continue
very
focal;
3) limited
potential
for additional
their efforts
to improve
the quality
of SIAs,
particularly
in the campaigns
highest risk areas, so that all
quality
gains during

eligible children (particularly the youngest

children) are reached and immunised during
each SIA round;
WHO should work to accelerate the process of
regulatory approval of monovalent type 1 OPV
(mOPV1), with the aim of having a product
available for potential use in critical endemic
areas by early 2005 as an adjunct to the existing
eradication activities

Effects of mOPV1
Humoral immunity:
Circulating antibodies will prevent
paralytic disease (individual
protection)
Mucosal immunity:
Secretary antibody will prevent
replication and excretion (community
barrier to transmission)

Effects of mOPV1
Rationale for mOPV1 effectiveness

No interference from Sabin types 2 & 3

In tOPV, type 2 most immunogenic, will

outgrow types 1+3

With mOPV1, first dose against type 1

With tOPV, first dose mainly against type 2

mOPV for Key Reservoirs

Marked increase in
individual immunity.
Up to 50% decrease
in subsequent
excretion
Increased secondary
spread.

Protection after 1 dose of

mOPV vs. tOPV (for type 1
polio)

John TJ, Devararjan LV, Balasubramanyan A. Immunization in India with trivalent and
monovalent oral poliovirus vaccines of enhanced potency. Bull WHO 1976;54:115-7.

Magnitude of mOPV1 Effect:

Seroconversion after 1 mOPV Dose

Caceres VM, Sutter RW. Sabin monovalent oral polio vaccines: Review of past experiences
and their potential use after polio eradication. Clin Infect Dis 2001;33:531-41.

Magnitude of mOPV1 Effect:

Decrease in Excretion after Challenge, Oman
Proportion Excreting PV

Overall
Reduction

tOPV

mOPV

16.4%

9.6%

Ref.

41.5%

Sutter RW et al. Trial of a supplemental dose of four poliovirus vaccines. N Eng J Med 2000;343:767-73.

Comparison:

Percent

tOPV Immunogenicity, India

John TJ, Devararjan LV, Balasubramanyan A. Immunization in India with trivalent and
monovalent oral poliovirus vaccines of enhanced potency. Bull WHO 1976;54:115-7.

Potential Implications:
mOPV1 vs tOPV

Percent

tOPV eradicated poliovirus type 2 in India

(worldwide) in 1999;
Type 1immunogenicity
mOPV1 similar
Typeto
2 type 1
as tOPV for type 2

mOPV1 Risks
Only type-specific immunity induced
Development of type 2 + 3 immunity delayed

Rare cases of vaccine-associated

paralytic poliomyelitis (VAPP)
Risk of VAPP following mOPV1 much lower
than following tOPV

mOPV1 Summary
Quality of campaigns continues to
determine coverage ("reaching all
children")
mOPV1 provides higher type-specific
immunity per contact than tOPV
against type 1 ("immunity gain per
contact")

3-dose tOPV Immunogenicity

Percent

(median seroconversion of developing country studies)

Patriarca PA et al. Factors affecting the immunogenicity of oral poliovirus

vaccine in developing countries: A review: Rev Infect Dis 1991;13: 926-39.

Enhanced-Potency TOPV + mOPVs

1 TOPV = 42%
2 TOPV = 66%
3 TOPV = 80%

"Rule of thumb"
1 dose of mOPV =
3 doses of TOPV
John TJ, Devararjan LV, Balasubramanyan A. Immunization in India with trivalent and
monovalent oral poliovirus vaccines of enhanced potency. Bull WHO 1976;54:115-117.

Seroconversion by Potency after

one Dose of mOPV1
Industrialized

Developing
country

No inferiority between one dose of

mOPV and one dose of TOPV
One dose of TOPV buys ~20-35%
seroconversion in developing countries
Caceres VM, Sutter RW. Sabin monovalent oral polio vaccines: Review of past experiences
and their potential use after polio eradication. Clin Infect Dis 2001;33:531-41.

One Dose of Four Vaccines at 9 Months

of Age, Oman (IPV, US-OPV, EU-OPV, mOPV3)
Sutter et al. Trial of a supplemental doses of four
Poliovirus vaccines. N Engl J Med 2000;343:767-73.

Seroprevalence after IPV

Poliovirus type 1 = 100%
Poliovirus type 2 = 100%
Poliovirus type 3 = 97%

Potential Adverse Events

Enhanced-potency TOPV:
Unknown: Vaccine-associated paralytic poliomyelitis (VAPP)
mOPV:
Risk of VAPP better quantified (experience from Hungary 1961-1981)

Type

Recipient Contact
#
#

Total recipient
(risk per 106)

Contact (risk
per 106)

0.27

0.19

3.62

27

2.49

4.97

Risk of type 1 cVDPV emergence in low-coverage areas

IPV:
Injection-related adverse events

mOPV Use in TOPV Era

Routine vaccination:
Hungary: from 1959 to late 1980s early 1990s;
campaigns of 1, 3, 2 (105 TCID50 each dose)
South Africa: mOPV1 as first routine dose for
~5 years in late 1980s and early 1990s (600,000
TCID50)
Kuwait: mOPV1 as first routine dose in 1970s &
1980s (data to be compiled)

mOPV1
potency
Campaign use:

Hungary:
100,000
TCID
Gaza
50
from 1979
-. (annual
campaigns)

South Africa:
600,000 TCID50
Outbreak
control:
Netherlands in 1977

New Eradication Tools

To stop polio transmission
'monovalent'
OPV protects
2 x faster.

To confirm polio infection

New lab
methods confirm
polio 2 x faster.

New Egypt Trial Data

Data on enhanced efficacy of mOPV1

vs. trivalent OPV, India 1997-2006*
Assumption

No routine
tOPV

First three
doses routine
tOPV

Vaccine

Location

Vaccine efficacy (%)

(95% CI)

trivalent

ROI

21 (15 - 26)

Bihar

14 (4 - 24)

UP

10 (6 - 13)

ROI

NA

Bihar

41 (0 - 71)

UP

28 (16 - 39)**

ROI

NA

Bihar

50 (0 - 81)

UP

31 (18 - 42)**

monovalent

monovalent

** significantly better than trivalent vaccine in UP

In endemic countries, Polio remains a disease

of very young children (P1 cases UP, 2006)
In endemic areas >85%
of cases are in children
aged <3 years

* data as on 9th December 2006

In India (UP & Bihar) an immunity gap in young

children can sustain transmission

IMMUNE

SUSCEPTIBLE
Age group (months)

Bivalent OPV (bOPV)

co-circulation

of type 1 and type 3 in

all polio-endemic and some reinfected countries
a formulation has simplified SIA
logistics and more effectively induce
serotype-specific immunity.
In 2009, clinical trial done in India (in
Indore, Pune and Chennai)
Polio Eradication

Bivalent OPV (bOPV)

compared

seroconversion to each
serotype in the bivalent OPV with that of
the monovalent and trivalent OPV
The trial showed bOPV was superior to
tOPV (20% higher seroconversion) and
almost as effective in achieving protection
as the respective mOPVs
Recommendations for use of bOPV made
by ACPE
Polio Eradication

Bivalent OPV Use

Where there is no compromised OPV

efficacy
(Nigeria/Pakistan/Afghanistan)

Where both indigenous WPV1 and

WPV3 circulate. bOPV should
complement tOPV SIAs to optimize
population immunity
Type-specific mOPVs should
continue to be used to stop
transmission of WPV1 and WPV3 in
poliovirus reservoirs

Polio Eradication

Bivalent OPV Use

Where there is compromised OPV efficacy

(Northern India)

The primary strategy for interrupting WPV1

transmission is mOPV1 SIAs. Periodic bOPV
SIAs should be used to maintain immunity
against WPV3.
After WPV1 is interrupted, mOPV3 SIAs should
be used to interrupt WPV3 transmission, with
periodic bOPV SIAs to maintain immunity
against WPV1.
Two tOPV SIAs per year should continue to
complement the use of mOPVs and bOPV by
maintaining population immunity against type 2
poliovirus.
Polio Eradication

Bivalent OPV Use

In countries at high risk of WPV

importations
(Nepal; countries in importation belt in
sub-saharan Africa)

bOPV SIAs should be used to

complement tOPV to optimize
population immunity against all
three serotypes.

Polio Eradication

Bivalent OPV Use

In Re-infected countries)

mOPVs should be used to stop

transmission of imported WPVs in
areas where one serotype is
circulating. bOPV should be used
in areas where an imported WPV1
and WPV3 are co-circulating.
Polio Eradication

First Use of bOPV,

Afghanistan, December
2009

Polio Eradication