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DTaP-IPV//Hib combined vaccine: near 10 years clinical experience:

The importance of the National Surveillance System and the vaccination schedule

Esteban ORTIZ, MDsanofi pasteur internationalLyon, France

esteban.ortiz@sanofipasteur.comesteban.ortiz@sanofipasteur.com

DTacP-IPV//Hib combined vaccine

IntroductionVaccine-preventable Diseases: achivements

Impact of the National Surveillance

Combined vaccine : Clinical Experience in Europe

Conclusion

Vaccine-preventable Diseases: achivements

Global Wild Polio Eradication

The former Czechoslovakia was the first country in the world to achive and scientifically demonstrate nationwide eradication of poliomyelitis (Slonim D, 2005).

In the Czech Republic, poliomyelitis has been eradicated since 1960 (Slonim D, 2005).

Since then, no case of poliomyelitis has been reported with the exclusive use of OPV vaccine.

Slonim D.- Epidemiol Mikrobiol Imunol. 2005 Aug;54(3):99-108.

Global Wild Polio Eradication

(2005, 2006?)Africa(200…)(2005, 2006?)SE Asia(200…)

(2005, 2006?)East Mediterranean(200…)

(2002)Europe199920.10.00Western Pacific199720.08.91Americas1991

Free of PolioWHO RegionLast Case

of Wild Polio

Paula Kriz, Vera Lebedova and Cestmir BenesEuroSurveillance Report 2005, 18 (7): http://www.eurosurveillance.org/ew/2005/050728.asp#4

Introducing universal hepatitis B vaccination in Europe: differences still remain between countries

Type of universal hepatitis B vaccination programme in the European Region of the World Health Organization, 2004 (Source: N Emiroglu and A Lobanov, WHO Euro, Copenhagen, Denmark)

WHO:http://www.eurosurveillance.org/ew/2004/041118.asp

Hepatitis B control

Universal Hep B vaccine dose given at birth is of high public health importance:

in infants born to HBsAg seropositivemothers, or

in mothers with unknown status, or

in cases where the screening errors occur.

Goldstein et al *Division of Viral Hepatitis, Centers for Disease Control and Prevention, Atlanta, GA 30333, USA

Int J Epidemiol. 2005 Dec;34(6):1329-39)

Importance of vaccination scheduleat 0-1-6 mo/o vs 2-4-6 mo/o.

1 052 mIU/mL[804;1377]

99.0% [94.3 ; 99.4]

Group 2Hep.B at 2-4-6

3 643 mIU/mL[2872;4620]

100% [97.2 ; 100]

Group 1Hep.B at 0-1-6

GMTs

Anti-HBs ≥ 10 mIU/mL

Greenberg D et al.- Ped. Inf. Dis. Journal. 21(8):769-776, August 2002

Results: Anti-HBs Post-dose 3

Post-dose 2 (at 2 months of age): Anti-HBs ≥ 10 mIU/mL in 47% of infants of group 1 versus only 9% in group 2

DTacP-IPV//Hib combined vaccineProduced by sanofi pasteur

Clinical Experience

Sanofi pasteur DTacP-IPV//Hib

Vaccine composition per dose of 0.5 mL:Diphtheria toxoid ≥ 30 IUTetanus toxoid ≥ 40 IUPertussis Antigens

PT 25 µgFHA 25 µg

Inactivated Polio virus type 1 40Dtype 2 8 Dtype 3 32 D

Lyophilized PRP 10 mcg(conjugated to approximately 20 mcg tetanus protein)

Sanofi pasteur DTacP-IPV//Hib

DTaP Diphtheria toxoid, Tetanus toxoid, PT & FHA Pertussisantigens (DTacP) Vaccine

ActHIB™ Lyophilized (PRP-T or Hib) Haemophilus influenzaetype b tetanus conjugate Vaccine

IMOVAX Polio™ (eIPV) enhanced Inactivated PolioVirus Vaccine

Tetravac™ / Tetraxim™ DTacP-eIPV Vaccine

Pentavac™/Pentaxim™ DTacP-eIPV//Hib Vaccine

Sanofi pasteur DTacP-IPV//Hib

The combined vaccine is licensed: since 1997 in several members states of the European Union under the trade name of Pentavac™in at least 45 countries worldwide (as Pentaxim™ or Pentavac™)is approved for three-dose primary and/or booster vaccinations

Sanofi pasteur DTacP-IPV//Hib

What can we learn from this experience ?Pre-licensure development has to meet pre-defined hypotheses,

–does the vaccine work ?whereas post marketing surveillance will tell us what the real world is :

–is the vaccine useful for the population?

Sp’s DTaP-eIPV//Hib: ImmunogenicityImmunogenicity1 Month After Third Dose (Pooled Data From 3 Consistency Lots)1 Month After Third Dose (Pooled Data From 3 Consistency Lots)

** Percent seroprotection (SP) or vaccine response (VR) for pertussis antigens.

A % SP or VR** 100 100 93.0 88.4 100 99.0 99.5 97.6

Anti- Anti-Group Parameter D T PT FHA 1 2 3 0.15

Anti-Pertussis Anti-Polio

B % SP or VR** 100 100 87.3 89.2 100 99.5 100 99.1

Anti-PRP

Group A: DTaP-IPV//Hib mixed administrationGroup B: DTaP-IPV + Hib separate administration

Country: France

Sp’s DTaP-IPV//Hib Anti-PT (EU/mL) GMTsStudy E2I01 (primary vaccination, France)

2,5 2,2

56,7 55,7

0

20

40

60

Pre-Dose 1 Post-Dose 3

DTacP-IPV + Hib

DTacP-IPV//Hib

GMT

Sp’s DTaP-eIPV//Hib Anti-FHA (EU/mL) GMTsStudy E2I01 (primary vaccination, France)

5 4,9

129

109

0

50

100

150

Pre-Dose 1 Post-Dose 3

DTacP-IPV + Hib

DTacP-IPV//Hib

GMT

** Percent seroprotection (SP) or vaccine response (VR) for pertussis antigens.

A % SP or VR** 100 100 89.6 89.5 100 100 100 98.0

Anti- Anti-Group Parameter D T PT FHA 1 2 3 0.15

Anti-Pertussis Anti-Polio

B % SP or VR** 100 100 90.8 92.5 100 100 100 98.1

Anti-PRP

Group A: DTaP-IPV//Hib mixed administration at 2, 3 and 4 months of ageGroup B: DTaP-IPV//Hib mixed administration at 2, 4 and 6 months of age

Country: France

Sp’s DTaP-eIPV//Hib: ImmunogenicityImmunogenicity1 Month After Third Dose 1 Month After Third Dose (Data From 2, 3 & 4 mo/o (Data From 2, 3 & 4 mo/o versusversus 2, 4 & 6 mo/o)2, 4 & 6 mo/o)

Sp’s DTaP-eIPV//Hib: Study E2I02 (Post-primary vaccination, France)

Percentage of Medical Contacts/Attention within 8 daysafter any dose of the 3-dose primary vaccination

8

0,8

7,7

0,6

0

10

20

30

40

50

DTaP-IPV (N= 3211) DTPa-IPV// Hib (N= 3254)

Any

Related to vaccination%

DTacP-IPV//Hib combined vaccineProduced by sanofi pasteur

Post-Marketing Clinical Experiencein Europe

1986-87

-88-89 -90

-91-92

-93-94

-95-96

-97-98

-992000

-01-02

-032004

0

500

1000

1500

DTPa

Year

Vaccination

Numberof cases

Pertussis in Sweden 1986-2004;culture-confirmed cases per month

CultureCulture--confirmed pertussis in infantsconfirmed pertussis in infantsbefore and after 1996before and after 1996

No

of

case

s

Age (months)

Before and after introduction of DTPaat 3, 5 and 12 months

0

20

40

60

80

100

120

140

160

0 1 2 3 4 5 6 7 8 9 10 11

2004200320022001200019991998199419931992

No dose 51 260 112 218(< 3 months)

1 dose 33 460 72 215(3 - < 5 months)

2 doses 114 260 20 17.5(5 - <12 months)

3 doses 410 830 18 4.4(12 – 60 months)

Person-yearsfollow-up

Decreaseof incidence

1%

92%

98%

Incidence of pertussis cases* in sp’s DTaP-IPV//Hib cohort

*Case definition: ≥ 21 days of spasmodic cough + culture and/or PCR confirmed cases

Sweden, 1997-2003

Numberof cases

Incidence /100 000

person-year

National Hib surveillance in SwedenDetail of the years 1997-2004

020406080

100120140

pre-va

cc av

erage

1997

1998

1999

2000

2001

2002

2003

2004

Vacc < 10y

Unvacc+ unknown<10 yHib total

No.

of

notif

ied

case

s

Year

In sumary, EU DTP_based Vaccine Public use

Main DTacP_Pentavalent

Main DTacP Hexavalent

Main DTacP Pentavalent & some Hexavalent=France, Spain, Sweden, Grece

Main DTwP_based

Main DTacP Hexavalent & some Pentavalent=Germany, Italy

Conclusion(s)

National Surveillance System:Essential for policy decision makersEssential for eventual changes or NOT changes in the immunization programmes

Vaccination schedule(s):Essential in the control and eradication of diseases

– ex. Hep B classical vaccination schedule ensures the prevention of vertical and horizontal transmission

Concusion(s) : Sanofi pasteur DTacP-IPV//Hib

What can we learn from this experience ?Pre-licensure development has to meet pre-defined hypotheses,

– does the vaccine work ?» Yes, different clinical studies demonstrated the good

immunogenicity and safety profile of the vaccine

whereas post marketing surveillance will tell us what the real world is :

– is the vaccine useful for the population?» Yes, post-marketing clinical experience showed that the

vaccine is efficacious in the National ImmunizationPrograms.

Thank youfor your attention

Hepatitis B Birth Dose

Administration of a birth dose of hepatitis B vaccine is required for effective postexposure immuno-prophylaxis to prevent perinatal HBV infection. also provides early protection to infants at risk for infection after the perinatal period. has been associated with higher rates of on-time completion of the hepatitis B vaccine seriesserves as a "safety net" to prevent perinatal infection among infants born to HBsAg-positive mothers who are not identified because of errors in maternal HBsAg testing or failures in reporting of test resultsIn certain populations, the birth dose has been associated with improved completion rates for all other infant vaccines

A Comprehensive Immunization Strategy to Eliminate Transmission of Hepatitis B Virus Infection in the United States Recommendations of the ACIP Part 1: Immunization of Infants, Children, and Adolescents MMWR December 23, 2005 / 54(RR16);1-23