Pneumococcal vaccines
Safety & Efficacy
Prof. Rajesh Kumar, MD
PGIMER School of Public Health
Chandigarh
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Pneumococcal vaccines
1911:
Clinical trials of whole-cell pneumococcal vaccine
conducted in South Africa
1938: Injection with purified capsular polysaccharides
provide clinical protection against type-specific disease
1983: 23-valent pneumococcal vaccine licensed
2000: 7-valent pneumococcal conjugate vaccine (PCV)
licensed in U.S.
2009: 10-valent PCV vaccine
2010: 13-valent PCV introduced
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Pneumococcal Polysaccharide Vaccine (PPSV)
• Polysaccharide antigen from 23 serotypes
– Effective in preventing the invasive pneumococcal disease (IPD)
• Safe vaccine; occasional local side effects
• Does not reduce nasopharyngeal carriage
• Does not provide herd immunity
• Recommended for persons aged ≥65 years and
people in certain high-risk groups aged 2 to 64 year
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Pneumococcal Conjugate Vaccines (PCV)
• PCV10 serotypes:
– 1, 4, 5, 6B, 7F, 9V, 14, 18C, 19F & 23F
• PCV13 serotypes:
 1, 3, 4, 5, 6A, 6B, 7F, 9V, 14,18C, 19A, 19F, 23F
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PCV Efficacy
Cochrane Systematic Review of seven studies1
Invasive pneumococcal disease (IPD):
Pooled vaccine efficacy (VE)
-
For Vaccine Serotypes-
80% (95% CI 58% to 90%, P <0.0001)
- For All Serotypes58% (95%CI 29% to 75%, P = 0.001)
1Lucero
MG, et al. Pneumococcal conjugate vaccines for preventing vaccine-type invasive pneumococcal disease and Xray defined pneumonia in children less than two years of age. Cochrane Database Syst Rev 2009;(4):CD004977.
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PCV Efficacy
Radiologically defined pneumonia
• Most studies report radiologically defined
pneumonia (standardized WHO definition)
- Pooled VE:
27% (95%CI 15% to 36%, P < 0.0001)
• Reduction in pneumonia even in studies that did
not follow WHO definition
1Skinner
JM, et al. Pre-clinical evaluation of a 15-valent pneumococcal conjugate vaccine (PCV15-CRM197) in an
infant rhesus monkey immunogenicity model. Vaccine 2011; 29:8870-8876.
2Madhi SA, et al. World Health Organization definition of “radiologically-confirmed pneumonia” may underestimate the true public health value of conjugate pneumococcal vaccines . Vaccine 2007;25(13):2413-9.
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PCV Efficacy
Clinically defined pneumonia
• Pooled PE: 6% (2% - 9%, P 0.0006)
• PCV vaccination reduces hospitalization in
virus-associated pneumonia; where disease severity
is increased by co-infection with pneumococcus1
1Madhi
SA, et al. The Vaccine Trialist Group. A role of Streptococcus pneumoniae in virus-associated
pneumonia. Nat med 2004;10:811-813.
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PCV Efficacy
Otitis media
• Efficacy of 10-50% against recurrent otitis media or for
prevention of tympanostomy tube placement1
• Pneumococcal isolates fell by 39% - 66% among
severe otitis media cases or from 'otitis-prone'
children2 ,3
1Fletcher
MA, et al. Brief review of the clinical effectiveness of PREVENAR against otitis media. Vaccine. 2007;
25(13):2507-12.
2 McEllistrem MC, et al. Acute otitis media due to penicillin-nonsusceptible Streptococcus pneumoniae before and after the
introduction of the pneumococcal conjugate vaccine. Clin Infect Dis 2005;40(12):1738-44.
3Block SL, et al.. Community-wide vaccination with the heptavalent pneumococcal conjugate significantly alters the
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microbiology of acute otitis media. Pediatr Infect Dis J 2004;23(9):829-33.
PCV Efficacy
Nasopharyngeal carriage
• Most of the available data are on PCV7
• Marked fall in vaccine-type pneumococcal carriage in
all age groups (23.7% to 26.8% at baseline to 7.1% to
8.5% post-vaccination)1
• Recent studies have reported effectiveness of PCV132
1Roca
A, et al. Effects of Community-Wide Vaccination with PCV-7 on Pneumococcal Nasopharyngeal Carriage in
The Gambia: A Cluster-Randomized Trial. PLoS Med 2011;8(10): e1001107.
2 Miller E, et al. Effectiveness of the new serotypes in the 13-valent pneumococcal conjugate vaccine. Vaccine.
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2011;29(49):9127-31.
Safety of PCV
• PCVs have a well tolerated and acceptable safety
profile1-3
• Main adverse events are injection-site reactions,
rash, headache, fatigue, joint pain, fever, decreased
appetite
• Serious rare events include bronchiolitis, pneumonia,
gastroenteritis in infants/toddlers
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Dicko A, et al. Primary vaccination with the 10-valent pneumococcal non-typable Haemophilus Influenzae protein D conjugate vaccine
(PHiD-CV) in infants in Mali and Nigeria: a randomized controlled trial. BMC Public Health 2011;11:882.
2 Amdekar YK, et al. Immunogenicity and safety of a 13-valent pneumococcal conjugate vaccine in healthy infants and toddlers given with
routine vaccines in India. Pediatr Infect Dis J. 2013 May; 32(5):509-16.
3 Lalwani S, et al. Immunogenicity, safety, and reactogenicity of the 10-valent pneumococcal non-typeable Hemophilus influenzae protein D
conjugate vaccine (PHiD-CV) when co-administered with the DTPw-HBV/Hib vaccine in Indian infants: a single-blind, randomized, controlled
study. Hum Vaccin Immunother. 2012 May;8(5):612-22.
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PCV: Efficacy vs Effectiveness
• Clinically relevant outcomes of public health significance
include: mortality, IPD, pneumonia, adverse effects/events
• Reduces the odds/risk of developing pneumonia, IPD by
vaccine serotypes and all-cause mortality (efficacy)
• Absolute risk reduction is much lower (effectiveness)
• No major adverse event except a small increase risk of
asthma
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Mathew JL, et al. Effectiveness versus efficacy of conjugated pneumococcal vaccine: a systematic review of
randomised, controlled trials with meta-analysis examining absolute risk reduction and relative risk.
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Indian Scenario
• High case fatality (25-30%) of invasive pneumococcal
disease in all age groups1
• Pneumococcus is a predominant pathogen in community
acquired acute bacterial meningitis (61.8%)2
• High nasopharyngeal colonization (28%), and
• High rates of resistance to antibiotics in unvaccinated
HIV infected children3
1
Thomas K, et al. Invasive pneumococcal disease associated with high case fatality in India.J Clin Epidemiol.
2013;66(1):36-43.
2 Mani R, et al. Bacteriological profile of community acquired acute bacterial meningitis: a ten-year retrospective study
in a tertiary neurocare centre in South India. Indian J Med Microbiol. 2007;25(2):108-14.
3 Bhattacharya SD, et al. High rates of colonization with drug resistant hemophilus influenzae type B and
Streptococccus Pneumoniae in unvaccinated HIV infected children from West Bengal. Indian J Pediatr.
2011;78(4):423-9.
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Indian Scenario
• Efficacy trials on PCV10, PCV13 not conducted but
studies report immunogencity of these vaccines
• PCV13 and PCV7: similar safety & tolerability profiles1
• PCV10, PCV13 have been licensed and are available in
the private sector
• Pneumococcal vaccination not included in the Indian
National Immunization Schedule
1.Amdekar YK, et al. Immunogenicity and safety of a 13-valent pneumococcal conjugate vaccine in healthy infants and toddlers given with routine
vaccines in India. Pediatr Infect Dis J. 2013;32(5):509-16.
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Way Forward
• Introduction of PCV in National Immunization Schedule
• Surveillance of pneumococcal serotypes
• Better diagnostic tools needed to monitor burden of
disease
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Thanks
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