PNEUMOCOCCAL CONJUGATE VACCINES FOR ADULTS

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PNEUMOCOCCAL CONJUGATE VACCINES FOR ADULTS
ISSUES AND CHALLENGES
Peter R. Paradiso, Ph.D. Wyeth Vaccines
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Pneumococcal Conjugate for Adults Issues
Challenges

• CONJUGATE VACCINES WILL HAVE LESS SEROTYPE
  COVERAGRE THAN PS (23 valent)
• Measuring the benefit of improved efficacy vs.
  coverage
• How will conjugates be used in the context of PS
• CAN EFFICACY TRIALS BE DONE?
• Invasive disease vs. CAP
• With or without PS
• CAN CONJUGATES BE LICENSED ON THE BASIS OF
  IMMUNOGENICITY?
• What measures?

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Issues with the PS Vaccine

• Duration of Immunity
• What age to give the first dose?
• When / if to give subsequent doses
• How to monitor
• Hypo-responsiveness

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Pneumococcal Conjugate Product Profile

• Efficacy
• Invasive disease
• CAP
• Can give repeated / periodic immunizations
• (any time relative to last conjugate or
  PS)
• No hypo-responsiveness

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Immunogenicity Issues

• What are the best measures?
• ELISA / OPA / Responders
• What does priming mean in an adult?
• Boost vs. reimmunizing
• Do conjugate vaccines prime or boost?
• Are certain serotypes in the PS less efficacions?
• Are those the target for conjugate?

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Estimated IPD efficacy of 23-valent PncPS vaccine
Estimated Efficacy () plus 95 C.I.)
Based on 2837 cases, 515 in vaccinees (median age
57)
Butler et al JAMA 1993
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Most Common Serotypes causing Invasive Disease in
gt 65 y olds, USA, 1998 (n1031)
coverage
of IPD
NR
Robinson et al 2001 JAMA
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Relative Efficacy of Most Common Serotypes
causing Invasive Disease in gt 65 y olds in the
U.S.
60-80 efficacy
40-60 efficacy
no significant efficacy
coverage
of IPD
NR
Robinson et al 2001 JAMA
contained in the 23-valent PncPS vaccines
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Immunogenicity of PS Vaccine Most Common
Serotypes causing Invasive Disease in gt 65 y olds
in the U.S.
60-80 efficacy
40-60 efficacy
no significant efficacy
coverage
of IPD
NR
Robinson et al 2001 JAMA
contained in the 23-valent PncPS vaccines
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Immunogenicity of Conjugate Vaccines in
non-infant populations

• Absolute Response to Conjugate
• In naïve and previous PS vaccinees
• Response to conjugate or polysaccharide booster
• ELISA vs. OPA vs. responders
• Serotype specificity

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Hodgkins Patients/7-OMPC/mean age 39, n38/group
Chan et al JID 1996
IgG (ug/ml)
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Immunogenicity of an 11V conjugate in healthy
adults Wuorimaa et al. (2001)
IgG (ug/ml)
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PncCRM OS 5-V Priming for PS Booster Response in
50-85 year old adults
Powers et al JID 1996
6 Month Interval N23/group
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Immunogenicity (OPA) of PncPS-CRM 7-V or PS in
Sickle Cell Children Adults (n12/group)
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6B
9V
23F
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18C
19F
Vernacchio et al JID 2000
8 Weeks Interval mean age 13 yrs
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PncPS-CRM 7-V Priming for PncPS Booster Response
(OPA) in Sickle Cell Children Adults
(n12/group)
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6B
9V
23F
18C
19F
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8 Weeks Interval mean age 13 yrs no boost by
ELISA
Vernacchio et al JID 2000
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Ability of Specific Serotypes to Elicit an ELISA
response in PncPS non-Responder Populations
Children 2-13 yr olds n17 PnuImune
of children with gt1.3 mg/ml or 4-fold rise
Sorensen PIDJ 1998
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Ability of Conjugates to Elicit an ELISA
response in PS non-Responder Populations
Children 2-13 yr olds n17 PncCRM7 Pnu-Imune
of children with gt1.3 mg/ml or 4-fold rise
Sorensen PIDJ 1998
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Conclusions

• Data derived from very small data sets and may be
  serotype dependent
• Conjugate can induce a response in adults even if
  previously primed with PS vaccine
• Conjugate can prime for a boost with either
  another conjugate dose or a PS vaccination
• Suggestion that poorly immunogenic PS serotypes
  may respond to conjugate
• There is little data in the elderly target
  population
• Is there relevance to data in healthy adults?