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

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tal d

ose

s of fo

ur

Po

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s vaccin

es. N

En

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ed

20

00

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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