In the United States, more than 30,000 organ transplants are performed each year, and more than 100,000 individuals are actively waitlisted for transplantation. Owing to their underlying comorbidities and anti-rejection therapy, which is immunosuppressive, solid organ transplant (SOT) recipients are uniquely vulnerable to severe illness and complications due to a wide range of infections, many of which are vaccine-preventable. Thus, any provider that encounters transplant recipients or candidates in their practice should be prepared to discuss vaccines and identify and prioritize opportunities for vaccination with these individuals, both before and after transplantation.
There are several factors that influence the choice, timing and administration of vaccines in adult SOT candidates and recipients, along with current recommendations on vaccines for selected infectious diseases.
General Principles
As a rule, SOT recipients have a less robust immune response to most vaccines compared with the general population. This is likely due to a combination of factors, including age, the underlying comorbidities that resulted in organ failure and led to transplantation, and most importantly, the immunosuppressive therapy they are receiving to prevent or treat rejection. Furthermore, these patients are usually most vulnerable to infection in the months immediately following transplantation, and vaccines administered during this period are also likely to be even less effective. Thus, whenever possible, it is preferable to administer recommended vaccines prior to transplantation.
When vaccines are indicated after transplantation, patients should be counseled that they may need to receive higher doses or booster doses of certain vaccines to achieve meaningful or similar levels of protection to the general population and that their response to vaccination may need to be assessed by follow-up laboratory testing. Finally, close contacts of transplant recipients should be counseled about the need to be up-to-date on their vaccines to minimize the risk of transmission to the patient.
Some vaccines may also pose risks that are unique to immunocompromised individuals, including SOT recipients. Live vaccines, such as the measles-mumps-rubella (MMR), varicella, yellow fever, intranasal influenza, oral rotavirus or oral typhoid vaccines, are contraindicated in adult transplant recipients because of the risk of disease associated with the live or attenuated pathogen contained in the vaccine. If these vaccines are indicated, they should only be administered prior to transplantation.
Adjuvanted vaccines, such as the adjuvanted influenza vaccine (Fluad®), recombinant herpes zoster subunit vaccine (Shingrix®) and adjuvanted hepatitis B vaccine (Heplisav-B®), contain an ingredient designed to stimulate the immune system and thereby generate a more robust (and protective) immune response – these vaccines carry a theoretical risk of triggering organ transplant rejection and ideally should be administered in collaboration with the patient’s transplant team and with a plan for close monitoring after vaccination.
Vaccines to Prioritize in SOT Recipients
Influenza Vaccine. Transplant recipients have a higher risk of complications – such as pneumonia – as well as hospitalization and death due to influenza compared to the general population, and they are a priority group for annual influenza vaccination according to the Centers for Disease Control and Prevention (CDC) Advisory Committee on Immunization Practices (ACIP). Multiple influenza vaccine formulations are available, including inactivated standard dose (contains 15 μg of antigen), high dose (contains 60 μg of antigen) and adjuvanted products, as well as the live-attenuated influenza vaccine (LAIV).
Other than excluding LAIV as an option for SOT recipients (for the reasons noted previously), the CDC, American Society of Transplantation (AST) and other expert groups do not give a preference for any influenza vaccine formulation over another. However, high-dose and adjuvanted vaccines do elicit a more robust immune response and should be considered in those transplant recipients who are age-eligible (i.e., ≥65 years).
Importantly, close contacts of transplant recipients should be strongly encouraged to receive their influenza vaccines annually as well – although it is preferred that these close contacts receive an inactivated vaccine, this is not a requirement as there have not been any documented transmissions of the virus contained in LAIV to an immunocompromised individual.
Pneumococcal Vaccine. Streptococcus pneumoniae is the most common bacterial cause of pneumonia, meningitis, sinus and middle ear infections globally, and in immunocompromised hosts it is more likely to cause severe invasive disease. Transplant recipients should be prioritized for pneumococcal vaccination per ACIP and AST guidelines, as should individuals listed for organ transplant who are likely to have underlying medical conditions (such as chronic heart, lung, kidney or liver disease) that also make them vulnerable to severe or invasive pneumococcal infections.
There are two pneumococcal vaccine formulations currently available, and these include the pneumococcal conjugate vaccine 13-valent (Prevnar®, PCV13) and the pneumococcal polysaccharide vaccine 23-valent (Pneumovax®, PPSV23). The ACIP has published detailed guidance about the appropriate order and number of doses of both vaccines for various priority groups who may have varying pneumococcal vaccine exposure histories – two guiding principles of administration are that adult patients should only receive a single dose of PCV13 in their lifetime, and that PCV13 should precede PPSV23 whenever possible.
Transplant recipients who have not been previously vaccinated should receive a dose of PCV13 followed eight weeks later by a dose of PPSV23, followed by a second dose of PPSV23 five years later. Patients who have already received PPSV23 in the past (without PCV13) should wait at least one year before receiving their first dose of PCV13.
Zoster Vaccine. Herpes zoster, or shingles, is caused by reactivation of latent varicella-zoster virus (VZV) that may have been acquired in childhood (most individuals born in the U.S. before 1980) or through receipt of the live attenuated varicella, or chickenpox, vaccine (first recommended by the ACIP for use in children in 1995).
Owing to their immunosuppressive therapy, transplant recipients are at an elevated risk of VZV reactivation and associated complications, which may include post-herpetic neuralgia (PHN), post-zoster soft tissue infections and disseminated disease such as pneumonia, hepatitis and meningoencephalitis.
Virtually all SOT recipients are prescribed antiviral prophylaxis for the first few months after transplant to prevent the reactivation of latent herpesviruses, including VZV. Individuals who are listed for transplant with no prior history of varicella or varicella vaccination or who are seronegative may be eligible to receive the live attenuated varicella vaccine – notably, this live vaccine is contraindicated after transplant. The recombinant herpes zoster subunit vaccine has been proven in clinical trials to confer excellent protection against zoster as well as PHN and has been shown to elicit a robust immune response in age-eligible (i.e., ≥50 years old) transplant recipients and those with comorbidities that may be on the waitlist.
COVID-19 Vaccines. SARS-CoV-2 infection has been associated with significant morbidity and mortality in SOT recipients. As such, AST, the American Society of Transplant Surgeons, the International Society for Heart & Lung Transplantation and The Transplantation Society have all recommended COVID-19 vaccination for SOT candidates and recipients and their close contacts.
At present, two vaccines are available under Emergency Use Authorization (EUA) in the United States – Moderna (an mRNA vaccine) and Janssen/Johnson & Johnson (replication-defective adenoviral vector vaccine) – and one, Pfizer-BioNTech (an mRNA vaccine) received full FDA approval in August 2021. All are considered appropriate for administration to transplant candidates and recipients. Whenever possible, vaccination should be completed at least two weeks prior to transplantation, and multi-society guidance suggests that the vaccine may be administered to unvaccinated SOT recipients between 1-3 months following transplantation.
Data regarding COVID-19 vaccine responses in SOT recipients is evolving. Available evidence suggests that antibody responses to these vaccines are diminished compared to the general population but that cellular responses may be present in the absence of a detectable antibody.
At this time, assessment of vaccine-induced antibody response is not recommended in SOT recipients. Further, booster doses are not recognized under the current EUAs but could be considered in the context of a clinical trial. Until additional data are available, SOT recipients should continue to adhere to preventative measures, including masking and frequent hand washing. [This appears to have changed since this was written – do you need to go back to dr. to get this section updated? https://www.fda.gov/news-events/press-announcements/coronavirus-covid-19-update-fda-authorizes-additional-vaccine-dose-certain-immunocompromised]
Vaccines to Prioritize in Patients Listed for SOT
Hepatitis B Vaccine. Completion of the hepatitis B vaccine series and development of protective antibody titers aids in the prevention of hepatitis B acquisition in the post-transplant setting. Transplant candidates should be vaccinated against hepatitis B using any of the available vaccine formulations, including the adjuvanted vaccine (HepB-CpG) or three- or four-dose series, though high-dose vaccine (40µg) should be considered for those on dialysis. For individuals who may be transplanted prior to completion of the series, an accelerated schedule could be considered; however, accelerated schedules appear to be less immunogenic. Hepatitis B surface antibody titers should be assessed four weeks after the last dose of vaccine, and revaccination should be considered in non-responders.
Varicella Vaccine. Primary varicella infection has been associated with significant morbidity in SOT recipients, and VZV serostatus should be assessed prior to transplantation. It is recommended that seronegative adult transplant candidates receive one dose of the varicella vaccine followed by serologic testing to assess vaccine response. An additional dose of vaccine may be given to non-responders, though timing of vaccination is a significant consideration, as live virus vaccines should be completed four weeks prior to transplantation. More recent data suggest that use of the recombinant subunit herpes zoster vaccine (Zostavax®) is safe and immunogenic in VZV-seronegative SOT recipients, though data regarding its use in seronegative transplant candidates is limited.
MMR Vaccine. Transplant recipients who are not immune to measles, mumps and rubella are at risk of acquisition of these infections during travel or during a local outbreak. It is recommended that MMR serology be evaluated prior to transplant and that seronegative candidates undergo vaccination.
Seronegative adults should be given one dose of MMR with subsequent assessment of antibody response. An additional dose may be provided to non-responders if time permits. As with all live virus vaccines in adult transplant candidates, four weeks should elapse between vaccine administration and transplantation.
Additional Vaccines. All transplant candidates should be up-to-date with age-appropriate vaccines in accordance with ACIP recommendations. In addition to the aforementioned vaccines, candidates should receive the Tdap, H. influenza type B and human papillomavirus vaccines as appropriate.
Special Considerations
Assessment of the immunization status of SOT recipients who intend to travel abroad, particularly to areas of increased risk for infectious disease acquisition, is of critical importance. Patients should be up-to-date on all routine vaccines, including the hepatitis B vaccine, and undergo evaluation for travel-specific vaccines, including the hepatitis A, inactivated typhoid and meningococcal vaccines as appropriate. Notably, yellow fever, dengue and oral typhoid vaccines are live attenuated vaccines and are contraindicated in SOT recipients.Â
SOT candidates and recipients are vulnerable to severe illness and complications due to a wide range of infections, many of which are vaccine-preventable. It is therefore imperative to ensure that vaccination needs are assessed across the transplant continuum and close contacts are prioritized for recommended vaccines.
Given the potential for diminished vaccine response following transplantation, completion of recommended vaccinations in the pre-transplant setting (and ideally as early into their disease course as possible) may reduce the burden of vaccine-preventable illness following transplant.
References
- Danziger-Isakov L, Kumar D, et al. Vaccination of solid organ transplant candidates and recipients: guidelines from the American Society of Transplantation Infectious Diseases Community of Practice. Clin Transplant 2019; 33: e13563.
- ACIP Recommended Adult Immunization Schedule by Medical Condition and Other Indications, United States, 2021. Vaccines Indicated for Adults Based on Medical Indications | CDC
- AST COVID-19 Vaccine FAQ Sheet: 2021 05 18 COVID19 VACCINE FAQS-final update.pdf (myast.org)
- Joint AST/ASTS/ISHLT Statement about Vaccine Efficacy in Organ Transplant Recipients: Updated Joint AST/ASTS/ISHLT Statement about Vaccine Efficacy in Organ Transplant Recipients. | American Society of Transplantation (myast.org)
Doctors Varun Kishor Phadke and Stephane M. Pouch
Dr. Phadke is a transplant infectious diseases physician and assistant professor of medicine at Emory University. He received his medical degree from Harvard Medical School, completed his residency training in internal medicine at New York-Presbyterian Hospital, Columbia University Medical School, and his fellowship in infectious diseases at Emory University. He also completed a National Institutes of Health-funded fellowship in vaccinology at Emory and is an investigator and staff physician at the Emory Vaccine and Treatment Evaluation Unit.
Dr. Pouch is a transplant infectious diseases physician and associate professor of medicine at Emory University. She received her MD from Temple University School of Medicine in 2007, completed her internship and residency in internal medicine at the University of Chicago, served as a chief resident at the John H. Stroger, Jr. Hospital of Cook County, and completed fellowship training in infectious diseases at NewYork-Presbyterian Hospital, Columbia University.
