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

2. 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

3. 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)

4. 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:

5. 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

6. 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/ /yr
( pneumococcal
bacteremia)
Invasive Pneumococcal Disease
PPV impact
PPV impact simulation: PPV administered at 65 years old; no revaccination Assumption: 30% of CAP is caused by S. pneumoniae PPV efficacy of 50% against IPD, 0% against pneumonia Adapted from Jokinen 1991 (Pneumonia in Eastern Finland in ) and Finish Ntl Register (Invasive pneumococcal disease in Finland in )

7. PPV Efficacy Against Pneumococcal Pneumonia in Clinical Trials*
Study, pub. yr.
Population studied
VE (95% CI)
MacLeod, 1945
Military recruits (US)
84% (54%, 94%)
Austrian, 1976
Young gold miners (S. Africa)
79% (65%, 88%)
Smit, 1977
92% (49%, 100%)
Riley, 1977
Young adults (PNG)
84% (<0%, 99%)
Simberkoff, 1986
Veterans (US)
<0% (<0%, 45%)
Koivula, 1997†
Elderly in community (Finland)
15% (<0%, 50%)
Örtqvist, 1998
Elderly in community (Swed)
<0% (<0%, 34%)
Honkanen, 1999 †
<0% (<0%, 20%)
*Studies utilizing ≤ 60µg of each capsular polysaccharide and > 200 participants
†PPV plus influenza vaccine cf. influenza vaccine alone

8. 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

9. 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:

10. 23PPV Responses in Elderly Reverse 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

11. 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

12. 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

13. 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

14. Pneumococcal Vaccination and Pneumonia
PPV has demonstrated a clear impact on pneumonia in young adults
PCV has demonstrated a clear impact on pediatric pneumonia

15. 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

16. 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

17. 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