Immunization in Kidney Transplantation

Lara Danziger-Isakov, MD, MPH

Associate Professor

Cincinnati Children’s Hospital Medical Center

Overview

• Importance of vaccination

• Vaccination of the transplant candidate

• Post-transplant vaccination

• Challenges in vaccination

WHY VACCINATE?

Reasons to Vaccinate

• Decrease risk in transplant patients

– Of vaccine-preventable diseases

– During outbreaks of vaccine-preventable diseases

– With use of emerging novel therapeutics

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

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

Slide courtesy of C Kotton

8

http://www.cdc.gov/measles/cases-outbreaks.html

Slide courtesy of C Kotton

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

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

CURRENT RECOMMENDATIONS:GENERALIZED VACCINATIONS

ACIP Recommendations 2014

14

ADULT VACCINE RECOMMENDATIONS 2015

HOW READY ARE CANDIDATES?

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)

CURRENT PRE-TRANSPLANT RECOMMENDATIONS

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.

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

https://www.merckvaccines.com/Products/Pneumovax/Pages/serotypes23

Slide Courtesy of C Kotton

21

Current Recommendations

• PCV13 (Prevnar®) & PPSV23 (Pneumovax®)

– New recommendations:

• PCV13 followed 8 weeks later by PPSV23 OR

• PPSV23 followed 1 year later by PCV13

22

Yellow Fever

• Pre-transplant vaccination

– Persistence of protective titers post-transplant

(2-32 years post-vaccination)

Wypsolz AJT 2013

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

Varicella Zoster virus

Varicella-Zoster Vaccine for the Prevention of Herpes Zoster,

NEJM, March 2007, p.1338Slide Courtesy of C Kotton

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

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

CURRENT POST-TRANSPLANT RECOMMENDATIONS

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

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

Vaccination Responses

Eckerle PLOS One 2013

Influenza H3N2 responses

Eckerle PLOS One 2013

CONTROVERSIES IN VACCINATION

Influenza responses

Danziger-Isakov, Transplantation 2010

Potential Indirect Effects

Danziger-Isakov, Transplantation 2010

De Novo anti-HLA antibodies

Katerinis, AJT 2011

Adjuvanted Vaccine

Schaffer, AJT 2011

CONCLUSIONS

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