file 001
DESCRIPTION
riskTRANSCRIPT
Global Polio Global Polio Eradication InitiativeEradication Initiative
POLIO VACCINESPOLIO VACCINESFacts about OPV Facts about OPV
Dr Benjamin Nkowane Dr Benjamin Nkowane WHO/HQWHO/HQ
STOP TEAM 37 TrainingAtlanta, May 2011
Polio Eradication
PART 1PART 1
POLIO VACCINES
Polio Eradication
MilestonesMilestones
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 IPoliovirus IGenus: Enterovirus, Family: PicornaviridaeNon-envelopedGenome: Single-stranded RNA of ~
7,500 nucleotides Three major antigenic sites (surface
proteins VP1-3)Three serotypes (1, 2, and 3)
Polio Eradication
Poliovirus IIPoliovirus IIRapidly 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
1950s Miracle: 1950s Miracle:
Salk & Sabin Salk & Sabin
VaccinesVaccines
Polio Eradication
Polio Eradication
VaccinesVaccines
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-introducedBivalent OPV introduced in 2009
Polio Eradication
Polio Eradication
OPV and IPV SchedulesOPV and IPV SchedulesWHO/EPI schedule requires 4 doses of
OPV at birth, 6, 10, 14 weeksSome 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 EventsAdverse EventsOPV
– 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
Cases of Paralytic Poliomyelitis (Total and Vaccine-Associated Cases),
United States, 1964-1992
0
20
40
60
80
100
120
64 66 68 70 72 74 76 78 80 82 84 86 88 90 92
Number of Cases
VAPP
Total
Polio Eradication
OPV ImmunogenicityOPV ImmunogenicityIndustrialized countriesIndustrialized 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 ImmunogenicityOPV ImmunogenicityDeveloping countriesDeveloping 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 & Advantages & DisadvantagesDisadvantages
Advantages– OPV
Ease of administration Price Mucosal immunity Secondary spread
– IPV No adverse events No VAPP
Disadvantages– OPV
VAPP Prolonged replication
in immune deficient persons
Risk of circulation after stopping OPV
– IPV Less mucosal
immunity Injection required Price
Polio Eradication
Poliovirus Antibody Seroprevalence Among Unvaccinated Inner-City Preschool Children, Detroit and Houston, 1990-1991
17
34
10
21
64
43
0
10
20
30
40
50
60
70
P1 P2 P3
Percent
12-23m 24-35m
7
2415
27
55
36
010203040506070
P1 P2 P3
Percent
12-23m 24-35m
Detroit Houston
Polio Eradication
Effect of Mass OPV Campaign outside of Study Effect of Mass OPV Campaign outside of Study District on Sero conversion to Poliovirus types 1, District on Sero conversion to Poliovirus types 1, 2, and 3 between Birth and 10 Weeks, Oman*2, and 3 between Birth and 10 Weeks, Oman*
01020
3040
5060
7080
90100
Type 1 Type 2 Type 3
1 IPV non-exposed1 IPV exposed
Percent
*J Infect Dis 175(Suppl 1):S215-27
Monovalent OPV
PART 2
-mOPV: a retired vaccine that was re-
commissioned-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
Informationbrochure 1962
Advisory Committee on Polio Eradication (ACPE), 21-22 Sep 2004
ACPE reviewed options reviewed for maximising immunity for each SIAs contact:
• Recommendations:– All polio infected countries should continue
their efforts to improve the quality of SIAs, particularly in the highest risk areas, so that all 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
ACPE deliberations on mOPV1 influenced by: 1)
type 2 eradicated globally; 2) type 3 circulation
very focal; 3) limited potential for additional
quality gains during campaigns
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
• Marked increase in individual immunity.
• Up to 50% decrease in subsequent excretion
• Increased secondary spread.
mOPV for Key Reservoirs
Protection after 1 dose of mOPV vs. tOPV (for type 1
polio)
0
25
50
75
100
tOPV mOPV
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
Sutter RW et al. Trial of a supplemental dose of four poliovirus vaccines. N Eng J Med 2000;343:767-73.
Proportion Excreting PV
tOPV mOPV
Overall 16.4% 9.6%
Reduction Ref. 41.5%
Comparison:tOPV Immunogenicity, India
29
67
31
50
89
52
65
96
67
0
10
20
30
40
50
60
70
80
90
100
Poliovirus type 1 Poliovirus type 2 Poliovirus type 3
Dose 1
Dose 2
Dose 3Pe
rce
nt
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
81
67
9789
100 96
0
10
20
30
40
50
60
70
80
90
100
mOPV1 tOPV
Pe
rce
nt
Type 1 Type 2
tOPV eradicated poliovirus type 2 in India(worldwide) in 1999; mOPV1 similar immunogenicity to 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(median seroconversion of developing country studies)
95
6572
0
10
20
30
40
50
60
70
80
90
100
Poliovirus type 1 Poliovirus type 2 Poliovirus type 3
Patriarca PA et al. Factors affecting the immunogenicity of oral poliovirus vaccine in developing countries: A review: Rev Infect Dis 1991;13: 926-39.
Pe
rce
nt
Enhanced-Potency TOPV + mOPVs
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.
1 TOPV = 42%2 TOPV = 66%3 TOPV = 80%
"Rule of thumb"1 dose of mOPV = 3 doses of TOPV
Seroconversion by Potency after one Dose of mOPV1
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.
Developingcountry
Industrialized
No inferiority between one dose of mOPV and one dose of TOPV
One dose of TOPV buys ~20-35% seroconversion in developing countries
One Dose of Four Vaccines at 9 Months of Age, Oman (IPV, US-OPV, EU-OPV, mOPV3)
Su
tter e
t al. T
rial o
f a su
pp
lem
en
tal d
ose
s of fo
ur
Po
lioviru
s vaccin
es. N
En
gl J M
ed
20
00
;34
3:7
67
-7
3.
Seroprevalence after IPVPoliovirus type 1 = 100%Poliovirus type 2 = 100%Poliovirus type 3 = 97%
Potential Adverse EventsEnhanced-potency TOPV:Unknown: Vaccine-associated paralytic poliomyelitis (VAPP)
Type Recipient #
Contact #
Total recipient (risk per 106)
Contact (risk per 106)
1 3 0 0.27 0
2 2 5 0.19 3.62
3 27 8 2.49 4.97
mOPV:Risk of VAPP better quantified (experience from Hungary 1961-1981)
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)
– Campaign use:• Gaza from 1979 -…. (annual campaigns)
– Outbreak control:• Netherlands in 1977
mOPV1 potencyHungary: 100,000 TCID50
South Africa: 600,000 TCID50
New Eradication Tools
To confirm polio infection
New labmethods confirmpolio 2 x faster.
'monovalent'OPV protects
2 x faster.
To stop polio transmission
0
25
50
75
'trivalent' OPV 'new' mOPV1
% children protected
against type1polio after a single dose
at birth.
New Egypt Trial Data
Data on enhanced efficacy of mOPV1vs. trivalent OPV, India 1997-2006*
Assumption Vaccine Location Vaccine efficacy (%)(95% CI)
trivalent ROI 21 (15 - 26)
Bihar 14 (4 - 24)
UP 10 (6 - 13)
No routine tOPV
monovalent ROI NA
Bihar 41 (0 - 71)
UP 28 (16 - 39)**
First three doses routine tOPV
monovalent ROI NA
Bihar 50 (0 - 81)
UP 31 (18 - 42)**
** significantly better than trivalent vaccine in UP
*
* data as on 9th December 2006
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
In India (UP & Bihar) an immunity gap in young children can sustain transmission
0%
10%
20%
30%
40%
50%
60%
70%
80%
90%
100%
0 to 4 5 to 8 9 to 12 13 ro16
17 to20
21 to24
25 to28
29 to32
33 to36
37 to40
41 to44
45 to48
49 to52
53 to56
57 to60
Age group (months)
IMMUNE
SUSCEPTIBLE
Polio Eradication
Bivalent OPV (bOPV)Bivalent OPV (bOPV)co-circulation of type 1 and type 3 in
all polio-endemic and some re-infected 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)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 Bivalent OPV Use Where there is no compromised OPV Where there is no compromised OPV
efficacyefficacy(Nigeria/Pakistan/Afghanistan) (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 Bivalent OPV Use Where there is compromised OPV efficacyWhere there is compromised OPV efficacy
(Northern India) (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 Bivalent OPV Use In countries at high risk of WPV In countries at high risk of WPV
importationsimportations(Nepal; countries in importation belt in (Nepal; countries in importation belt in
sub-saharan Africa) sub-saharan Africa)
bOPV SIAs should be used to complement tOPV to optimize population immunity against all three serotypes.
Polio Eradication
Bivalent OPV Use Bivalent OPV Use In Re-infected countries) 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, First Use of bOPV,
Afghanistan, December Afghanistan, December
20092009