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Pneumococcal Vaccine for Adults and Elderly Immunity, polysaccharides and conjugates. Jan T. Poolman, Ph.D. Director, Bacterial Vaccines R&D. VRBPAC November 17, 2005. Adult pneumococcal immunization.

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pneumococcal vaccine for adults and elderly immunity polysaccharides and conjugates

Pneumococcal Vaccinefor Adults and ElderlyImmunity, polysaccharides and conjugates

Jan T. Poolman, Ph.D.

Director, Bacterial Vaccines R&D

VRBPAC November 17, 2005

adult pneumococcal immunization
Adult pneumococcal immunization
  • Polysaccharide immunization gives a substantial public health benefit mostly by impacting pneumococcal bacteremia
  • This benefit occurs even though PPV immunization has a marginal impact on total burden of adult/elderly pneumococcal disease because immunization only once >65 yrs and because low impact on pneumonia
ppv limitations
PPV Limitations
  • PPV licensed with the indication « pneumococcal infection »
  • Partial efficacy (appr. 50%) against invasive pneumococcal disease/bacteremia
  • Low efficacy against pneumococcal pneumonia in >65 yrs. Precise efficacy unknown due to underpowered studies, and difficulty to diagnose
  • Probably easier to protect against bacteremia as opposed to pneumonia
  • No policy of revaccination, uncertainty of lowered responses upon revaccination (hyporesponsiveness)
ppv revaccination
PPV Revaccination

« The limited data indicate older adults mount anti-CP antibody responses to revaccination, although the responses may be less than those to the initial injection of vaccine. If true, factors that may account for the hyporesponsiveness to revaccination include age, comorbidities, or … the initial vaccination. »

From : Artz et al. Pneumococcal Vaccination and Revaccination of Older Adults. Clin. Microbiol. Rev. 2003, 16:308-318

ppv ipd efficacy
PPV IPD Efficacy

Clinical Effectiveness of pneumococcal vaccination in preventing invasive pneumococcal disease in observational studies in older adults

From : Fedson D.S., Musher D.S. in « Vaccines », Ed. Plotkin S.A., Orenstein W.A.

Pub. Saunders/Elsevier, 2004, pp. 529-588

adult pneumococcal vaccine need for improvement

PPV impact

Adult Pneumococcal Vaccine: Need for Improvement

PPV : Substantial health benefit and marginal impact burden of disease

Pneumococcal Pneumonia (30% of CAP)

(nonbacteremic pneumococcal

pneumonia)

Cases/100.000/yr

( pneumococcal

bacteremia)

Invasive Pneumococcal Disease

PPV impact simulation:PPV administered at 65 years old; no revaccinationAssumption: 30% of CAP is caused by S. pneumoniaePPV efficacy of 50% against IPD, 0% against pneumoniaAdapted from Jokinen 1991 (Pneumonia in Eastern Finland in 1981-82) and Finish Ntl Register (Invasive pneumococcal disease in Finland in 1995-99)

ppv efficacy against pneumococcal pneumonia in clinical trials
PPV Efficacy Against Pneumococcal Pneumonia in Clinical Trials*

*Studies utilizing ≤ 60µg of each capsular polysaccharide and > 200 participants

†PPV plus influenza vaccine cf. influenza vaccine alone

why is the impact of ppv different in young adults versus elderly
Why is the impact of PPV different in young adults versus elderly?
  • Antibody level : impact of immunosenescence on the quantity of the immune (antibody) response
  • Opsonophagocytosis : impact of immunosenescence on the quality of the immune (antibody) response
  • Opsonophagocytosis : impact of immunosenescence on PMN functionality
slide9

Pneumococcal conjugate induced pediatric antibody levels and protection against IPD

0.18 µg/ml

From : Jódar L. et al. Serological criteria for evaluation and licensure of new pneumococcal conjugate vaccine formulations for use in infants. Vaccine. 2003, 21:3265-3272

slide10
23PPV Responses in ElderlyReverse cumulative curve for aggregated responses (11 polysaccharides pooled)

-50 % IPD efficacy in elderly after PPV

-50% of elderly achieve ~5 µg/ml anti-PS after PPV

GSK Biologicals

Unpublished data

slide11

Geometric Mean Concentrations (GMCs [µg/ml]) post-dose 1 (ELISA) in young adults (18-45years) and elderly subjects ( 65years) vaccinated with 23-valent PPV

 = Significant

n = 25

slide12

Geometric Mean Titers (GMTs [µg/ml]) post- dose 1 (OPA) in young adults (18-45years)and elderly subjects ( 65years)vaccinated with 23-valent PPV

 = Significant

n = 25

key messages
Key Messages
  • Higher anti-PS antibody levels are needed to prevent IPD in elderly as compared to pediatric, this may relate to:
    • IPD in adults usually associated with pneumonia; IPD in children is not
    • Responses to PPV vs PCV
    • Significantly decreased PPV responses (OPA) are observed in elderly vs young adults
    • Immunosenescence in general
pneumococcal vaccination and pneumonia
Pneumococcal Vaccination and Pneumonia
  • PPV has demonstrated a clear impact on pneumonia in young adults
  • PCV has demonstrated a clear impact on pediatric pneumonia
pediatric 9 valent conjugate efficacy trials in south africa the gambia
Pediatric 9-valent conjugate efficacy trials in South Africa, the Gambia
  • Efficacy of vaccine serotypes against invasive pneumococcal disease:

83% (39-97) S. Africa

92% (44-100) the Gambia

  • Efficacy of vaccine serotypes against bacteremic pneumococcal pneumonia:

61% (16-82) S. Africa

70% (31-80) the Gambia

  • Efficacy of vaccine serotypes against pneumonia with proven bacteriology via lung aspirates:

73% (2-95) the Gambia

  • Bacteremia without focus is easier to prevent than pneumonia
targets for improvement
Targets for Improvement
  • Develop vaccines that induce stronger anti-PS immune responses as compared to the existing polysaccharide vaccine
  • Broaden the immunization age-range beyond the « one-shot at 65 »
  • Overcome hyporesponsiveness that appears to be associated with PPV in order to allow revaccination
keys for licensure of pcv
Keys for Licensure of PCV
  • Immuno-noninferiority (OPA & ELISA) vs. PPV in adults/elderly : IPD/bacteremia
  • Immuno-noninferiority (OPA & ELISA) vs. PPV in young adults : step towards pneumococcal pneumonia
  • Response after revaccination is NI to response after primary vaccination