Immunizations in kidney

1. Immunization in Kidney Transplantation
Lara Danziger-Isakov, MD, MPH
Associate Professor
Cincinnati Children’s Hospital Medical Center

2. Overview
• Importance of vaccination
• Vaccination of the transplant candidate
• Post-transplant vaccination
• Challenges in vaccination

3. WHY VACCINATE?

4. Reasons to Vaccinate
• Decrease risk in transplant patients
– Of vaccine-preventable diseases
– During outbreaks of vaccine-preventable diseases
– With use of emerging novel therapeutics

5. Impact of Vaccine-Preventable Disease
• Immunocompromised adults are at increased risk for
infectious and complications of
– Pneumococcal disease (>20X higher compared to adults
without high-risk medical conditions)
– Influenza
– Varicella
• May complicate post-transplant treatment
regimens
– Hepatitis B

6. Impact during outbreaks
• Recent outbreaks of vaccine-preventable
illness in the United States
– Measles 2014-15
– Mumps 2009-10, 2011-13, 2014
– Pertussis 2012-14

7. 7
Slide courtesy of C Kotton

8. 8
http://www.cdc.gov/measles/cases-outbreaks.html
Slide courtesy of C Kotton

9. Emerging Novel Therapy Use
• Eculizumab (Soliris®)
– Monoclonal antibody approved for Paroxysmal
Nocturnal Hemoglobinuria) & Atypical hemolytic
uremic syndrome
• Investigational use for antibody-mediated
rejection (AMR)
– Terminal complement pathway inhibitor
– Associated with risk of meningococcal disease

10. http://highered.mcgraw-hill.com/sites/dl/free/0071402357/156712/figure127_3.html
Protection from meningococcal disease involves both antimeningococcal immunoglobulins and
complement. Activation of complement by antimeningococcal IgM or IgG promotes bacterial lysis via
the membrane attack complex (C5–C9), while C3b [produced by alternative, mannose-binding lectin
(MBL), or classic pathway activation] and antimeningococcal IgG2 cooperate to produce effective
opsonophagocytosis. A neutrophil defect in binding IgG2 (the FcγRIIA R131 allele) has been
associated with more severe meningococcal disease.
CR1, complement receptor 1; LOS, lipooligosaccharide.
Slide courtesy of C Kotton
Eculizumab

11. CURRENT RECOMMENDATIONS:
GENERALIZED VACCINATIONS

12. ACIP Recommendations 2014

14. 14
ADULT VACCINE RECOMMENDATIONS 2015

15. HOW READY ARE CANDIDATES?

16. TABLE 1. Estimated proportion of adults aged ≥19 years who received selected vaccinations, by age group, high-risk
status,* race/ethnicity, and other selected characteristics — National Health Interview Survey, United States, 2012
Vaccination, age group Sample size % (95% CI)
Pneumococcal vaccination, ever
19–64 yrs, high risk 9,333 20.0 (18.9–21.1)
≥65 yrs 7,076 59.9 (58.4–61.4)
Tetanus vaccination, past 10 yrs
19–49 yrs 16,927 64.2 (63.2–65.1)
50–64 yrs 8,525 63.5 (62.1–64.8)
≥65 yrs 6,905 55.1 (53.6–56.7)
Tetanus vaccination including pertussis vaccine,
past 7 yrs
≥19 yrs 22,653 14.2 (13.6–14.9)
19–64 yrs 17,695 15.6 (14.9–16.4)
≥65 yrs 4,958 8.0 (7.0–9.1)
Hepatitis A vaccination (≥2 doses), ever***
19–49 yrs 14,834 12.2 (11.5–13.0)
Hepatitis B vaccination (≥3 doses), ever†††
19–49 yrs 15,649 35.3 (34.3–36.2)
≥60 yrs, overall 1,907 15.1 (12.9–17.4)
Herpes Zoster (shingles) vaccination, ever§§§
≥60 yrs 9,924 20.1 (19.1–21.2)

17. CURRENT PRE-TRANSPLANT
RECOMMENDATIONS

18. Danziger-Isakov AJT 2013; Rubin CID 2013; KDIGO AJT 2009
Kidney Disease: Improving Global Outcomes
(KDIGO) Transplant Work Group. KDIGO clinical
practice guideline for the care of kidney
transplant recipients. American Journal of
Transplantation 2009; 9(Suppl 3): S1–S157.

19. VACCINATION AST ID
Guidelines
IDSA Guideline KDIGO
Hepatitis A Yes Yes
Hepatitis B Yes Yes Yes
Haemophilus influenza b (HIB) Yes Yes
Diphtheria/Tetanus/Pertussis Yes Yes
Human papilloma virus Yes (11-26 y) Yes (11-26 y)
Influenza Inactivated Yes Yes Yes
Live-attenuated No No
Measles/Mumps/Rubella Yes Yes
Meningococcal Yes Yes
Pneumococcal Conjugate Yes Yes
Polysaccharide Yes Yes
Polio Inactivated Yes Yes
Varicella Yes Yes
Zoster Yes (50+ y) Consider >50 y
Yellow Fever Yes Yes
Danziger-Isakov AJT 2013; Rubin CID 2013; KDIGO AJT 2009

20. https://www.merckvaccines.com/Products/Pneumovax/Pages/serotypes23
Slide Courtesy of C Kotton

21. 21

22. Current Recommendations
• PCV13 (Prevnar®) & PPSV23 (Pneumovax®)
– New recommendations:
• PCV13 followed 8 weeks later by PPSV23 OR
• PPSV23 followed 1 year later by PCV13
22

23. Yellow Fever
• Pre-transplant vaccination
– Persistence of protective titers post-transplant
(2-32 years post-vaccination)
Wypsolz AJT 2013

24. Eculizumab & Meningococcal Prevention
• Meningococcal Vaccination
– Two doses of vaccine, optimally >2 weeks before
transplant
• Menactra® – protein conjugate vaccine
– Covers serogroups A, C, Y, and W-135
– Serogroup B under development
• Replaces older polysaccharide vaccine
– Consider for all “highly sensitized”, h/o humoral
rejection, or anticipated need for eculizumab
• Prophylaxis with eculizumab use
– TMP/SMX, amoxicillin or ciprofloxacin have been used
– Duration unknown, depends on eculizumab course
Slide Courtesy of C Kotton

25. Varicella Zoster virus
Varicella-Zoster Vaccine for the Prevention of Herpes Zoster,
NEJM, March 2007, p.1338
Slide Courtesy of C Kotton

26. Zoster Vaccine
• Shingles Prevention Study Group
– 38,546 subjects ≥60yo
– Followed for ~ 3 years
– Zoster incidence 51% lower in vaccinees
• 5.4 vs 11.1 cases/person-years, P<0.001
– Post-herpetic neuralgia decreased by 67%
– Median duration of pain lower
• 21 vs 24 days, P=0.03
Oxman NEJM 2005

27. Zoster vaccine
• Recommended for those ≥ 60 y.o.
• Approved for those ≥ 50 y.o.
• Consider before immunosuppression
– Give at least a month before anticipated transplant
– Defer depending on other medications/conditions
• Steroids (> 20 mg daily prednisone equivalent)
• Adalimumab, infliximab, and etanercept
• Pre-existing cellular immune deficit
MMWR 2008

28. CURRENT POST-TRANSPLANT
RECOMMENDATIONS

29. CURRENT RECOMMENDATIONS:
POST-TRANSPLANT
VACCINATION AST ID
Guidelines
IDSA Guideline KDIGO
Hepatitis A Yes Yes At-risk
Hepatitis B Yes Yes Yes
Haemophilus influenza b (HIB) Yes Yes Yes
Diphtheria/Tetanus/Pertussis Yes Yes Yes
Human papilloma virus Yes (11-26 y) Yes (11-26 y)
Influenza Inactivated Yes Yes Yes
Live-attenuated No No No
Measles/Mumps/Rubella No No No
Meningococcal Yes Yes At-risk
Pneumococcal Conjugate Yes Yes
Polysaccharide Yes Yes Yes
Polio Inactivated Yes Yes Yes
Varicella No No No
Zoster No No
Typhoid Vi (inactivated IM) Yes Yes/At-risk
Yellow Fever No No
Danziger-Isakov AJT 2013; Rubin CID 2013; KDIGO AJT 2009

30. Yellow Fever
• 19 subjects vaccinated post-transplant
– 14 Kidney recipients
– Variety of immunosuppressive regimens
– 1/19 with localized pain at injection site
– No systemic reactions
Azevedo TID 2011

31. Vaccination Responses
Eckerle PLOS One 2013

32. Influenza H3N2 responses
Eckerle PLOS One 2013

33. CONTROVERSIES IN VACCINATION

34. Influenza responses
Danziger-Isakov, Transplantation 2010

35. Potential Indirect Effects
Danziger-Isakov, Transplantation 2010

36. De Novo anti-HLA antibodies
Katerinis, AJT 2011

37. Adjuvanted Vaccine
Schaffer, AJT 2011

38. CONCLUSIONS

39. Summary
• Vaccination is important
• Evaluation of vaccination status should occur
early pre-transplant
• Pre-transplant vaccination likely more
immunogenic than post-transplant
– Also, can give live-viral vaccines pre-transplant
• Continual reassessment of vaccination status
is necessary