Pneumococcal Conjugate Vaccine for Immunocompromised Patients

1. Pneumococcal Conjugate Vaccine for Immunocompromised Patients Donna M. Ambrosino, M.D. Professor and Director Massachusetts Biologic Laboratories University of Massachusetts Medical School

2. Risk and Immune Response to Polysaccharides Age (i.e., elderly) Other immunocompromised groups

3. Protective Response Documented toDecline with Age Production of high affinity antibodies a Long-lasting memory response to immunization b DTH to antigens seen in earlier life c a Goidl, et al. J. Exp. Med. 144, 1037 (1976) b McElhaney, et al. J. Gerentol. Med. Sci. 47, MS (1992) c Roberts-Thomson, et al., Lancet ii, 368 (1974)

4. Controversial Observation(i.e., conflicting data exists) CD4 / CD8 ratio change during adulthood IL4 production changes during adulthood IFN-gamma production changes during adulthood NK activity changes during adulthood

5. Rates of Invasive Pneumococcal Disease by Age GroupUnited States, 1998

6. Immunocompromised Patient Groups To Be Discussed Asplenics Hodgkin�s Disease Patients Sickle Cell Patients HIV Patients BMT Patients

7. Rate of Invasive Pneumococcal Disease By Underlying Disease Category

8. Special Considerations for Vaccine Strategies for Immunocompromised Patients Who to immunize? Cost implications Immunogenicity When to immunize? Timing relative to transplant Timing relative to disease progression Timing relative to splenectomy Which vaccine to use? 23-valent Conjugate Both

9. Old Myths Die Hard Asplenics actually respond relatively well to Polysaccharides

10. IgM and IgG Antibody Responses to Capsular Polysaccharides of Hib and Pneumococcal Serotypes

11. Recommendations for Asplenics Use 23-valent vaccine For children < 5 years (at least 2 doses of conjugate followed by 23-valent)* Caveat: For ITP patients on steroids, would immunize after splenectomy when off steroids * Red Book 2003 (p. 498)

12. Total anti-HIB Antibody Concentrations in Patients with Hodgkin�s Disease Displayed by Time Since Diagnosis

13. Priming with 7-OMPC Conjugate Vaccine Followed By 23-valent in Patients treated for Hodgkin�s Disease

14. Sickle Cell Pneumococcal IgG ELISA Data

15. Functional Antibody Responses to Pneumococcal Vaccines in Children and Young Adults with Sickle Cell Disease

16. Antibody Responses to Pneumococcal Vaccines among HIV-infected Adults

17. Recommendations for Older SCD / HIV Patients Conjugate followed by 23-valent may increase responses No official recommendation to use conjugate for these groups for those > 5 years

18. Ps Vaccines and Hematopoietic Cell Transplants (i.e., bone marrow, stem cell, etc.) Series of studies for HIB and Pneumo Conjugate Vaccines

19. Rationale for Immunizations after HCT Infections are common after HCT Delayed recovery of immune function Defects in humoral and cell mediated immunity Decline in protective immunity to vaccine-preventable diseases

20. Antibody Concentrations to Vaccine-Preventable Diseases Before and After BMT

21. Effect of Donor Immunization on Antibody Responses in Allogeneic BMT

22. Effect of Pre-harvest Immunization with HIB-conjugate Vaccine in Autologous BMT

23. Pneumococcal Infections after HCT Estimates of pneumococcal disease after HCT range from 2% - 36% Median time of occurrence is 9 - 15 months Allogeneic HCT and chronic GVHD are associated with higher risk for sepsis

24. Occurrence of Pneumococcal Infection After Blood or Marrow SCT

25. Molrine et al (Blood, 2003)Randomized Study of Allogeneic Patients To examine whether immunization with a 7-valent pneumococcal conjugate vaccine (PCV7) is immunogenic in BMT patients To examine the effect of donor immunization with PCV7 on antibody responses of patients immunized after BMT

27. Comparison of Antibody Responses to Vaccine Serotypes of HCT Patients with Immunized Donors to those with Unimmunized Donors

29. Comparison of Percent Protected to All Seven Vaccine Serotypes After HCT Serotype-specific IgG Pn Ab > 0.5 ?g/ml Donor Group 3 mos 6 mos 12 mos 13 mos Immunized 57% 67% 60% 75% Unimmunized 54% 36% 35% 64% p value NS 0.05 NS NS Serotype-specific IgG Pn Ab > 1.00 ?g/ml Donor Group 3 mos 6 mos 12 mos 13 mos. Immunized 43% 42% 50% 65% Unimmunized 23% 7% 15% 56% p value NS 0.007 0.02 NS

30. Antibody Responses to PCV7 Compared to PPV23 at 13 Months Post HCT Geometric Mean IgG (?g/ml) Serotype P value 4 0.0001 6B 0.0001 9V 0.0001 14 0.0001 18C 0.0001 19F 0.022 23F 0.0001

31. Study Conclusions Donor immunization with pneumococcal conjugate vaccine enhances antibody responses early after HCT Three doses of pneumococcal conjugate vaccine are immunogenic in HCT patients regardless of donor immunization

32. Current CDC Recommendations for Polysaccharide Immunization after HCT Three doses of HIB-conjugate vaccine at 12, 14 and 24 months after HCT Two doses of 23-valent pneumococcal polysaccharide vaccine (PPV23) at 12 and 24 months after HCT. MMWR 2000; 49(No. RR-10): 84-85

33. Our Recommendations Immunization with 7-valent pneumococcal conjugate vaccine should be considered for allogeneic HCT patients and replace use of 23-valent pneumococcal polysaccharide vaccine* Donor immunization should be used when possible to maximize early benefit for HCT patients *Red Book 2003, �Some experts recommend multiple-dose schedule of pneumococcal conjugate and/or polysaccharide vaccine at 12 and 24 months.�

35. Comparison of Immunization Schedules after SCT

36. Materials and Methods Vaccine 7-valent Pneumococcal Conjugate (PCV7, Wyeth Lederle Vaccines) includes serotypes 4, 6B, 9V, 14, 18C, 19F, 23F conjugated to protein carrier CRM197 Antibody Assay IgG ELISA standardized with controls and reagents qualified by WLVP