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Pre-transplant Vaccination: a Model for Optimal Patient Care

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Deepali Kumar MD MSc FRCPC
Transplant Infectious Diseases & Multi Organ Transplant Program
University Health Network
Toronto, Ontario, Canada

Vaccines have been the single most important public health intervention in the last century. Vaccination of transplant candidates and recipients is sometimes given little thought especially when the urgency of transplant and the transplant workup takes precedence. However, immunization is a very simple way to prevent hospitalization and mortality in transplant recipients and should be a routine part of our pre-transplant evaluation. The benefits of immunization can start immediately. Consider the relatively common scenario of a donor with previous Hepatitis B infection (anti-HBc positive and anti-HBs positive). A Hepatitis B immune transplant candidate has a significantly lower risk of HBV transmission than someone who is unimmunized.

What immunizations are important? When should they be given? And do they work in the setting of immunosuppression?

Invasive Pneumococcal disease in organ transplant patients occurs at a rate 25 times greater than in the general population. Pneumococcal polysaccharide vaccine (PPV23) has long been considered the mainstay of disease prevention; however, the literature is controversial as to the effectiveness of this vaccine. More recent studies show that the pneumococcal conjugate vaccine (PCV13 originally licensed for infants and children) is immunogenic in transplant patients. Therefore, many public health authorities worldwide (including the U.S. Advisory Committee on Immunization Practices and the Public Health Agency of Canada) have recommended a dose of PCV13 followed by PPV23 at least 8 weeks later. The PPV23 will cover the additional common serotypes of pneumococcus that are not in PCV13. For those who have received PPV23 in the past, there needs to be a one year interval before the PCV13 dose.

Probably the most discussed vaccine is the influenza vaccine, perhaps because it is the only vaccine given every year. Influenza can lead to viral pneumonia, bacterial superinfection, and potentially chronic lung allograft dysfunction. There are now several forms of influenza vaccine (inactivated, live, adjuvanted, high-dose, intradermal) and various vaccine strategies have been studied. Several studies in transplant patients, done by our group and others show that intradermal vaccine, adjuvanted vaccine or booster doses do not offer more benefit with regards to immunogenicity than a standard dose of inactivated influenza vaccine. Studies done in the lung transplant population or larger studies with subgroups of lung transplant patients consistently show that this group has the lowest humoral responses to vaccine compared with other transplant patients. Therefore, in addition to immunizing transplant recipients, it is of utmost importance that health care workers and close contacts of these patients be immunized to prevent transmission to this vulnerable group. Due to the short-lived immunity provided by current influenza vaccines and the annual variation in strains, this vaccine is given yearly. Quadrivalent formulations (containing two A strains and two B strains of influenza) will likely replace the current trivalent formulations in the near future but will still need to be given yearly. Several studies have shown that influenza vaccination is safe post-transplant and does not induce alloreactivity.

Shingles (herpes zoster) is also more common after transplant and has a cumulative incidence of up to 20% at 5 years after lung transplant. A live-attenuated shingles vaccine was licensed in 2008 and can be given to those 50 years of age or older. However, the vaccine is contraindicated post-transplant because it is a live-attenuated vaccine. Pre-transplant administration could theoretically provide benefit post-transplant, but studies evaluating this are lacking; nevertheless, some centers recommend pre-transplant shingles immunization for the 50+ age group. Inactivated forms of herpes zoster vaccine are under development and may be an option for post-transplant patients.

HPV-related anogenital disease occurs at a higher frequency after transplant and can be very difficult to treat. Human papillomavirus (HPV) vaccines are effective in preventing cervical cancer and anogenital lesions in the general population. Although the age indications vary, HPV vaccine should be considered for pre-transplant patients that meet the age indication (generally age 9-45 in girls/women and 9-26 year old boys/men). The quadrivalent vaccine has been studied in a small cohort of young adult post-transplant recipients; only 55% of lung transplant patients had an antibody response to vaccine compared to 95% of kidney transplant patients. Although this vaccine covers the most prevalent types of HPV, other HPV types may also cause disease. Therefore, a 9-valent vaccine is under development and may be an option for transplant candidates and recipients.

In addition to these specific vaccines, it is important to ensure that routine immunizations for transplant patients are up-to-date prior to transplant. These include live virus vaccines (MMR, Varicella) if needed and other inactivated vaccines (Hepatitis B, tetanus, acellular pertussis, meningococcal etc. if indicated). Vaccine formulations vary from country to country so it is important to consult national guidelines.

Timing of immunization is also an important concept to understand. In general, vaccines given pre-transplant are more effective. Although diminished, any immunity generated pre-transplant is usually retained post-transplant. Immunizations given after transplant usually will be less effective. The use of induction immunotherapy with polyclonal antibody significantly reduces immunogenicity of vaccines for a period of several months. Therefore, it is recommended to wait 3-6 months after transplant to resume immunization. Similarly, the response to vaccines will be reduced after therapy for a rejection episode and significantly reduced with anti-CD20 monoclonal antibody (rituximab) therapy.

Although some vaccines such as Hepatitis B and HPV are given as multiple doses over a period of 6 months, transplant should not be delayed in order to complete the 6 month course. In general, the series can be started prior to transplant and completed post-transplant. As an alternative, Hepatitis B specifically can be given using accelerated schedules.

How can we incorporate this into practice? Setting up a pre-transplant clinic visit that allows for general infectious disease screening and vaccination can optimize pre-transplant care. A checklist of vaccines the patient needs is a helpful tool as is an immunization card that patients can carry with them. Many patients prefer to keep this information on their mobile phones in immunization 'apps'.

Disclosure Statement: the author has received research grants from Roche, Merck, and Astellas; speaker honoraria from Merck, Astellas, and Pfizer; consultancy fees from Oxford Immunotec and Roche.

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