PNEUMOCOCCAL CONJUGATE VACCINE SHABIR A MADHI

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PNEUMOCOCCAL CONJUGATE VACCINE
SHABIR A MADHI
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ACUTE RESPIRATORY INFECTIONS THE LEADING
INFECTIOUS CAUSE OF DEATH
3.5
Over age five
3.0
Under age five
2.5
2.0
Millions of deaths
1.5
1.0
0.5
0
Measles
Acute respiratory infections
AIDS
Diarrhoeal diseases
TB
Malaria
World Health Organization 1999
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BACTEREMIA IN CHILDREN WITH SEVERE
COMMUNITY-ACQUIRED LRTI
P0.0001
P0.07
P0.06
P0.02
CID July 2000
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ESTIMATED RELATIVE INCIDENCE RATES (/100 000) OF
SEVERE BACTERAEMIC PNEUMONIA
RR42.9 (20.7-90.2)
RR21.4 (9.4-48.4)
RR49.0 (15.4-156.0)
RR97.9 (11.4-838.2)
RR22.5 (13.2-37.6)
CID 2000
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AETIOLOGY OF MENINGITIS IN SOUTH AFRICAN HIV-1
UNINFECTED CHILDREN
Madhi SA et al, Int J Infect Dis 2001
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HISTORY OF PNEUMOCOCCAL VACCINE

• 1881 Pasteur and Sternberg -Pneumococcus
  isolated
• 1891 Klemperers- Protective effect of antiserum
• 1911 Wright- Whole-cell pneumococcal vaccine
• 1930 Francis- Purified polysaccharide antigenic
  in humans
• 1935 Polyvalent Pnc polysaccharide vaccine in SA
  mines
• 1938-46 Hexavalent polysaccharide vaccine
  (withdrawn)
• 1977 14-valent pneumococcal polysaccharide
  vaccine licensed
• 1984 23-valent pneumococcal polysaccharide
  vaccine
• 1999 Pneumococcal conjugate vaccine (7-9 valent)

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CHARACTERISTICS OF IMMUNE RESPONSES TO T-CELL
INDEPENDENT VS. T-CELL DEPENDENT ANTIGENS

• Polysaccharide antigen

• Protein-Polysachharide
• conjugate antigen

T cell independent
T cell dependent

• Production dysproportionate IgM
• Lack of immunological memory
• Short-lived immune response
• Failure to produce high affinity
• antibody

• Stimulate T-helper cell response
• Strong booster response upon
• re-exposure
• iii. High affinity antibody

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THE NEW GENERATION OF PNEUMOCOCCAL VACCINETHE
CONJUGATE VACCINE
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PNEUMOCOCCAL SEROGROUPS CAUSING IPD IN YOUNG
CHILDREN REPRESENTED IN 7-V PnCV FORMULATION
7-V Serogroups as of all IPD serotypes
Hausdorff et al (2000) CID 30100-21
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SEROGROUP DISTRIBUTION OF INVASIVE PNEUMOCOCCAL
ISOLATES AMONG HIV-1 INFECTED AND UNINFECTED
CHILDREN
7-V
9-V
11-V
7-Valent
9-Valent
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IPD ISOLATES IN CHILDREN lt 2 YRS OF AGE.
SEROGROUPS REPRESENTED BY 7- 9- 11-VALENT PnCV.

Meningitis
All disease
Bacteraemia
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EFFICACY OF THE PNEUMOCOCCAL CONJUGATE VACCINE
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EFFICACY OF PNCRM7 AGAINST INVASIVE DISEASE IN US
INFANTS (CALIFORNIA)
Black S, et al. PIDJ 2000
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VACCINE EFFICACY (INTENT-TO-TREAT ANALYSIS) FOR
VACCINE-SEROTYPE SPECIFIC INVASIVE PNEUMOCOCCAL
DISEASE
VE 72.1 82.5
65.4
(CI 95 46.1, 86.6) (CI 95 39.0 to 96.7)
(CI 95 23.8, 85.0)


NEJM, 349 14 2003
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VACCINE EFICACY AGAINST 1ST EPISODE OF ANTIBIOTIC
RESISTANT INVASIVE Pnc DISEASE
NEJM, 349 14 2003
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ACUTE RESPIRATORY INFECTIONS THE LEADING
INFECTIOUS CAUSE OF DEATH
3.5
Over age five
3.0
Under age five
2.5
2.0
Millions of deaths
1.5
1.0
0.5
0
Measles
Acute respiratory infections
AIDS
Diarrhoeal diseases
TB
Malaria
World Health Organization 1999
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DEFINING PNEUMONIA
Sens
Clinical diagnosis
Any X-ray abnormality
Lobar consolidation
Culture proven bacterial pneumonia
Spec
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ALVEOLAR CONSOLIDATION
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HIV UNINFECTED CHILDREN OVERALL EFFICACY AGAINST
PNEUMOCOCCAL PNEUMONIA (ITT)
37
4
1VAR vaccine attributable reduction per 100 000
person years
NEJM, 349 14 2003 Nature Med 2004. 10 811-813
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HIV INFECTED CHILDREN OVERALL EFFICACY AGAINST
PNEUMOCOCCAL PNEUMONIA (ITT)
40
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1VAR vaccine attributable reduction per 1 000
person years
NEJM, 349 14 2003 Nature Med 2004. 10 811-813
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EFFICACY OF 7V-PncCV AGAINST PNEUMONIA IN NORTH
AMERICAN CHILDREN (ITT)
Black S et al. PIDJ 2002
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EFFICACY OF PNEUMOCOCCAL CONJUGATE VACCINE
AGAINST ACUTE OTITIS MEDIA (PP)
Eskola J et al. NEJM 2001
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EFFICACY OF PNEUMOCOCCAL CONJUGATE VACCINE
AGAINST ACUTE OTITIS MEDIA (ITT)
Black S et al. PIDJ 2000
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IMPACT OF PNCV-9 ON CARRIAGE
Vaccination at 6, 10, and 14 weeks carriage
measured at 9 months.
Mbelle et al, JID, 1999
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CARRIAGE OF VT 6A IN DCC ATTENDEES AND IN
THEIR YOUNG SIBLINGS
Pnc vaccine
45

40
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Control

35
of all cultures at DCC (2,449 isolates)
30
25
20
20
RR 0.62 p lt 0.001
15
10
5
0
45
38
40
of all cultures of young siblings (150
isolates)
35
27
30
25
RR 0.70 p 0.034
20
15
10
5
0
Dagan R et al. ICAAC 2000
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RATES OF INVASIVE PNEUMOCOCCAL DISEASE IN CHIDREN
UNDER FIVE YEARS OF AGE
Whitney CG et al. NEJM 2003
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RATES OF INVASIVE PNEUMOCOCCAL DISEASE AMONG
UNVACCINATED ADULTS IN USA
Whitney CG et al. NEJM 2003
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CHANGES IN ESTIMATED RATES OF INVASIVE
PNEUMOCOCCAL DISEASE AMONG ADULTS
Whitney CG et al. NEJM 2003
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SUMMARY PNEUMOCOCCAL CONJUAGTE VACCINE

• Vaccine reduces invasive pneumococcal disease
  among HIV infected and uninfected children
• Impact on drug-resistant pneumococcal disease
• Impressive reduction against all-cause clinically
  diagnosed pneumonia in HIV-1 infected and
  uninfected children
• Potential for benefit o susceptible adult by
  vaccinating the child
• ???Affordability of vaccine
• ???Introduction into EPI

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EFFECT OF AGE ON EFFICACY OF 7V-PncCV IN
PREVENTING CXR CONFIRMED PNEUMONIA
Black S et al. PIDJ 2002
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AGE-SPECIFIC EFFICACY AGAINST WHO-AC PNEUMONIA
(ITT- HIV UNINFECTED CHILDREN)
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IMMUNE RESPONSES TO POLYSACHARIDE VS.
POLYSACCHARIDE-PROTEIN CONJUGATE VACCINES
Janeway-Travers Immunobiology
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TOPICS STILL TO BE ADRESSED AT CONFERENCE

• Does HIV infection status matter in determining
  the quantitative and qualitative antibody
  response to the PnCV????
• Is the efficacy measured by CXR-confirmed
  pneumonia truly reflective of the efficacy of the
  PnCV??? Use of CRP and procalcitonin in improving
  on the specificity of outcome measure.
• What is the relevance of age, disease spectrum
  and HIV infection status on coverage between the
  7 vs. 9 valent PnCV
• How has the vaccine helped us in determining the
  role of S. pneumonia in viral pneumonia????