1. Pneumococcal Vaccine Use Around the World: Successes and Challenges Adam L. Cohen, MD MPH Respiratory Diseases Branch, Division of Bacterial Diseases Centers for Disease Control and Prevention 44 th National Immunization Conference 21 April 2010

2. Global childhood deaths from pneumonia PneumoADIP / WHO

3. Leading infectious killers worldwide Deaths (millions) < 5 years old > 5 years old 0 0.5 1.0 1.5 2.0 2.5 3.0 3.5 Pneumonia AIDSDiarrheaTBMalariaMeasles 3.5 2.7 2.2 1.7 1.1 0.9 Source: WHO, 2000

7. Streptococcus pneumoniae

8. Anatomy of a pneumococcus Capsule  serotype (>90)

9. Pneumococcal conjugate vaccines in the United States Prevnar (Pfizer) 7-valent introduced into routine childhood immunization program in 2000 13-valent introduced in 2010 Poly- or oligosaccharides of serotypes 4, 6B, 9V, 14, 18C, 19F, and 23F in 7-valent 13-valent has 1, 3, 5, 6A, 7F, and 19A Conjugated to CRM197 (diphtheria toxin) Serotype coverage ~90% in N. America and Australia and 70% of all disease worldwide

10. Pneumococcal vaccine pipeline Clinical phase candidates Launched Clinical Trial Phase III Clinical Trial Phase II Clinical Trial Phase I 9-valent 7-valent 10-valent Prevnar 7-v Prevnar 13-v 11-valent Preclinical stage =Discontinued Based on publicly available information Pfizer (Wyeth) Sanofi Merck GSK** Intercell/PAT H IC47 protein antigen ** Technology Transfer to Fiocruz annouced August, 2009 for Brazil +Pfizer acquired Wyeth on October 16,2009 Common protein antigen 2189242A 11-valent

11. 11 PCV7 intro- duction Rates of invasive pneumococcal disease among children <5 years, 1998-2008 2008 vs. baseline All Serotypes: -79% PCV7 Types: -99% CDC, ABCs, 2008 data are preliminary

12. Time series analysis Nationwide Inpatient Sample Rates of all-cause pneumonia dropped 39% (-506/100,000) by 2004 in children <2 yrs Represents ~41,000 fewer pneumonias in 2004 Pneumococcal pneumonia dropped 65% Decline in pneumonia admissions after PCV7 introduction in children <2 Grijalva CG et al. Lancet 2007;369:1179-86

13. Clinical Trials Have Shown that PCV7 Is Effective Against Invasive Pneumococcal Disease & Pneumonia StudyOutcomeEfficacy % (CI) Black et al Hansen et al 38,000 infants, California PCV7, 4 doses Xray pneumonia20 (4, 34) Xray pneumonia (WHO defined)30 (11, 46) Vaccine-type invasive disease94 (80, 99) O’Brien et al 8,000 Native Amer <2 yo, US PCV7, 4 doses Xray pneumonia (WHO-defined)0 Vaccine-type invasive disease83 (21, 96) Klugman et al 40,000 infants, S. Africa; PCV9, 3 doses Xray pneumonia25 (4, 41) Vaccine-type invasive disease83 (39, 97): HIV neg 65 (24, 86): HIV pos Cutts et al 17,000 infants, The Gambia PCV9, 3 doses Clinical pneumonia7 (1, 12) Xray pneumonia (WHO-defined)37 (27, 45) Vaccine-type invasive disease77 (51, 90) Lucero et al 12,000 infants Philippines PCV11, 3 doses Xray pneumonia23 (-1, 42)

14. But is it all good news?

15. 15 PCV7 intro- duction Rates of invasive pneumococcal disease among children <5 years, 1998-2008 2008 vs. baseline All Serotypes: -79% PCV7 Types: -99% Type 19A: +233% CDC, ABCs, 2008 data are preliminary

16. IPD rates among Alaska Native children < 2 years old, by year Singleton RJ et al. JAMA 2007;297:1784-1792

17. What is herd immunity? (Indirect effects)

18. Susceptible Population

19. Herd immunity: Partially vaccinated population x xx

20. 20 Rates of IPD caused by all serotypes among adults >18 years-old, ABCs 1998-2008 PCV7 intro- duction 2008 vs. baseline 65+: -36% 50-64: -15% 18-49: -34% CDC, ABCs, 2008 data are preliminary

21. WHO vaccine recommendation

22. GAVI -- Global Alliance for Vaccines and Immunizations www.vaccinealliance.org

23. Cumulative Percent of Countries that Use Hib Vaccine

24. Proportion of Countries that use Hib Vaccine, by Income Level

26. What is an AMC? Advanced market commitment An upfront financial commitment by donors to subsidise purchase of vaccines at a set price if & when a vaccine meets minimum specified criteria and is demanded by an eligible country In return for industry commitments on dedicated supply and low prices (<$3.50 per dose) An AMC 'makes a market' as an incentive for investments in R&D, manufacturing capacity, and lower, predictable prices 26 Source: GAVI Source: GAVI Alliance; www.vaccineamc.org

28. Where are we now? Successes –Vaccine is effective in a number of settings –Impact seen in children and adults –Multiple vaccines are available with novel financing mechanisms Challenges –Effectiveness in low income countries is unknown –Concerns about replacement disease and herd effects –Financing still an issue, especially for middle income countries

29. Thank you. Adam L. Cohen, MD MPH Division of Bacterial Diseases, CDC dvj1@cdc.gov