The pre-transplant screening visit is an opportunity to evaluate a candidate's risk for infection, including checking select vaccine serologies, and provide counseling about safe living after transplantation (10, 14, 17). The immunization history from the infant in Case 1 reveals that he has only received one set of routine vaccines 2 months ago, thus checking vaccine titers is not necessary, and he should receive routine vaccines now. If he is still waiting for a heart transplant in 4 weeks, the third set of primary childhood vaccines can be administered as part of the accelerated schedule (Table 1). In general, after review of records and serologic responses to certain vaccines, a vaccine roadmap should be developed and implemented as noted in Table 1 with additional considerations for asplenia or other conditions (Table 2).

For vaccinated children, serology can be checked for Hepatitis B (HBV), Hepatitis A (HAV), varicella (VZV), and measles/mumps/rubella (MMR) (14). To have maximal benefit, inactivated vaccines should be given at least 2 weeks prior to transplant. It is recommended to have at least 4 weeks before transplant for safety of administering live vaccines (14). Given that the infant in Case 1 is only 4 months of age and requires a VAD, he likely has passive antibody that would render live virus vaccines, such as MMR and varicella, useless; likewise, he is also listed status 1A for heart transplant with the potential for transplant to occur within 4 weeks, and thus live vaccines should not be given.

Family members and close contacts of the SOT candidate should ensure they are up-to-date on their immunizations as well, including seasonal influenza and COVID-19 vaccines. The latter two vaccines are of critical importance in infants too young to be vaccinated themselves, such as in Case 1. Live vaccines are not contraindicated in close contacts with the exception of the smallpox and oral polio vaccines; the latter is not available in the United States. Contact precautions and hand hygiene should be used if the rotavirus vaccine or live-attenuated influenza vaccines are given. Likewise, if a rash develops after varicella vaccine, direct contact with the rash should be avoided until complete crusting occurs (18). Household pets should also have annual check-ups to ensure they are healthy and fully immunized (14). Vaccine specific recommendations are outlined below.

Hepatitis B (HBV) infection is highly prevalent worldwide and universal vaccination is recommended for all infants, children, and adolescents to prevent progressive liver damage (14, 19). Immunity against HBV should be confirmed prior to transplant (anti-HBs >10 IU/ml) as antibody titers can wane, particularly in immunocompromised individuals or those receiving chronic dialysis (14, 20). Assessing HBV immunity became part of the Organ Procurement and Transplantation Network (OPTN) policy in 2021. Future analysis will help assess vaccine efficacy, particularly in cases of HBV core antibody positive donors. In a retrospective study of pediatric SOT candidates, approximately half had indeterminate, non-reactive, or unavailable HBV surface antibody titers, even amongst those who had completed the primary vaccine series (20). Documentation of immunity is of particular importance in SOT recipients as donor-derived infection has been reported and adequate titers has been shown to prevent de novo HBV infection post-transplant (21). In non-immune individuals (anti-HBs <10 IU/ml), revaccination can be done with the complete series, using high-dose (40 µg) vaccine, or with giving one dose and re-checking anti-HBs (14). An adjuvanted two-dose HBV vaccine (HepB-CpG) with increased immunogenicity compared to existing vaccine formulations is available for individuals older than 18 years of age (22).

All pediatric SOT candidates and recipients should receive diphtheria, tetanus and pertussis containing vaccines using an acellular pertussis component (DTaP or TdaP) (14). Infants and children should receive 5 doses DTaP vaccines with minimal intervals specified in Table 1. Combination vaccines are available and can be used to reduce the number of overall injections. A single booster dose of Tdap should be administered to adolescents and Tdap should be given every 10 years throughout life for ongoing tetanus prophylaxis (19).

Haemophilus influenza type B (Hib) infections have declined dramatically since the introduction of the Hib vaccine (19). Immunocompromised individuals particularly those with asplenia or impaired splenic function are at particular risk for invasive infection (23). After completion of the series vaccine titers are not routinely checked.

Inactivated polio vaccine (IPV) should be administered to all SOT recipients and can be safely administered post-transplant, with minimal intervals specified in Table 1 (19). Oral polio vaccine stopped being used in the United States since 2000 given risk for vaccine-associated paralytic poliomyelitis in vaccine recipients or close contacts. Being up to date on IPV is underscored with the resurgence of polio in the United States and other countries in unvaccinated people (24). After completion of the series vaccine titers are not routinely checked.

Invasive pneumococcal disease (IPD) causes significant morbidity and mortality in children and can lead to bacteremia, pneumonia, endocarditis or meningitis (25). SOT recipients are at significantly higher risk for IPD, particularly those with asplenia or infants heart transplant recipients (3). Two types of pneumococcal vaccines are available, protein-conjugated vaccines and the 23-valent polysaccharide vaccine used in certain high-risk individuals. In June 2022, the CDC recommended the use of 15-valent pneumococcal conjugate vaccine (PCV15) in children; PCV20 was subsequently approved in June 2023 (25). PCV15 contains two additional serotypes (22F, 33F) and PCV20 also contains (8, 10A, 11A, 12F and 15B). In a Phase III trial (NCT03921424) of PCV15 in children infected with Human Immunodeficiency Virus (HIV), PCV15 was more immunogenic for 8 shared serotypes compared to PCV13, although specific data in SOT recipients is lacking (25). Current recommendations are for the use of either PCV15 or PCV20 for all infants and children as the primary series (Table 3). For SOT recipients who have not received any dose of PCV13, PCV15, or PCV20, a single dose of PCV15 or PCV20 is recommended ≥8 weeks after the most recent dose of pneumococcal vaccine (26). In children who receive PCV20, additional administration of PPSV23 is not needed.

Meningococcal disease caused by Neisseria meningitidis can cause bacteremia, meningitis or invasive infection particularly in high-risk individuals (27). Three quadrivalent conjugate vaccines against serogroups A, C, W, and Y (MenACWY) and two serogroup B meningococcal vaccines (MenB) are available. Vaccination with MenACWY is recommended for adolescents 11 or 12 years of age and infants older than 2 months at increased risk, such as those with complement deficiency, receipt of complement inhibitor, anatomic or functional asplenia, travel to a high risk area, or those with HIV (27). Vaccine should ideally be given at least 2 weeks prior to splenectomy or receipt of complement inhibitor. In the United States, MenB vaccine is recommended starting at 10 years of age in individuals at high-risk for meningococcal infection with a booster dose for those who remain at increased risk. Canadian and European Guidelines start as early as 2 months of age. For asplenic individuals, booster doses of MenACWY should be given every 5 years and MenB every 2–3 years (27). Transplant recipients receiving terminal complement inhibitors to treat antibody-mediated rejection are at particular risk for meningococcal disease and should be vaccinated prior to treatment.

Hepatitis A virus (HAV) is a communicable disease transmitted fecal-orally (28). Periodic outbreaks occur typically from contaminated foods. Immunocompromised individuals and those with underlying liver disease are at risk for severe infection and fulminant hepatitis. HAV vaccine should be administered to all SOT candidates and recipients, particularly liver transplant candidates (14, 28). Serologic response to HAV should be checked to ensure seroconversion (14).

Human papillomavirus (HPV) is a common sexually transmitted infection which can lead to the development of cervical, anogenital, and oropharyngeal cancers. SOT recipients have higher rates of HPV cancers compared to the general population (29). Vaccination against HPV has been routinely recommended since 2006 for females and 2011 for males (19). Two or three-doses of HPV vaccine are recommended starting as early as 9 years of age. While the vaccine is safe to be given post-transplant, immunogenicity may be reduced, particularly in lung transplant recipients likely related to degree of immunosuppression (30). Because of this, efforts should be made to optimize HPV vaccine pre-transplant.

Influenza causes severe infection in immunocompromised individuals and annual vaccination is strongly recommended for SOT candidate and recipients 9 months and older and their close contacts (31). Live attenuated influenza vaccine should not be given to SOT recipients given the theoretical concern for viral replication. Although current recommendations are the same as those for the general public, SOT recipients likely have decreased immune response to the influenza vaccine and may benefit from alternative strategies, such as high-dose influenza vaccine or an additional booster dose (14, 32, 33). The optimal timing of influenza vaccine administration post-transplant remains a topic of interest. Current recommendations are for the influenza vaccine to be given 3 months post-transplant, although it is often given as early as 1 month post-transplant when there is community spread.

A number of COVID-19 vaccines are approved and the most up-to-date recommendations can be found on the CDC and AST websites (34, 35). Vaccination against SARS-CoV-2 is strongly recommended for everyone 6 months and older, and ideally should be completed prior to transplantation. However, it can be given as early as 1–3 months post-transplant depending on community circulation. Three doses of an mRNA vaccine is recommended as the primary series for SOT recipients given decreased humoral and cellular immune response with two doses, although some SOT recipients will fail to mount any detectable humoral response even after booster doses (36). Current recommendations include age-appropriate bivalent booster dose to be given at least 2 months after the last dose of vaccine, although the CDC website should be consulted for the most up to-date information given the evolving nature of the COVID-19 pandemic.

Varicella vaccine (VZV) is a live-attenuated vaccine routinely administered as a 2-dose series at 12–15 months and 4–6 years of age, although the second dose can be given as early as 4 weeks after the first. While efficacy is not assured, infants can receive a dose at 6 months with a second and third dose given if transplant has not occurred by 12 months of age (13, 14). Passive antibody from blood products may interfere with efficacy and timing of vaccination should be based on CDC recommended time intervals, unless serology is negative (12). Serology should be checked prior to transplant. Efforts should be made to administer both doses of VZV vaccine prior to transplant given concerns for safety of live vaccine administration post-transplant until immunosuppression can be lessened. If vaccine is given and an organ becomes available within 4 weeks, acyclovir can be administered to prevent vaccine virus infection. After SOT, VZV vaccine administration can be considered in select individuals (Table 4) (12).

The live-attenuated measles, mumps, rubella (MMR) vaccine is typically given as a two-dose series at 12–15 months and 4–6 years of age. Similar to VZV vaccine, the second dose can be given with only a 4-week interval and for infants a dose can be given as early as 6 months of age. This should strongly be considered in infants not anticipated to be transplanted within 4 weeks, as post-transplant administration is generally contraindicated or may be considerably delayed (12). Early administration may result in reduced immunogenicity from immature immune responses and interfering maternal antibodies, and thus the two-dose series should be re-initiated if transplant has not occurred by 12 months of age and is not anticipated to occur within 4 weeks. Vaccine should be delayed an appropriate interval if blood products or immunoglobulin has been given due to interference with immune response. MMR serology should be checked prior to transplant.

In general, inactivated vaccines are safe to administer 3–6 months post-transplant, although the optimal timing depends on the individual circumstances and net immunosuppression (14). If the individual in case 2 were not up-to-date on any of her primary vaccine series, it would be important to administer them in an expedited schedule at this time (Table 1). Live vaccines have not traditionally been recommended post-transplant, however can be considered in select individuals who meet clinical and immunologic criteria listed in Table 4. There is increasing evidence for the safety and immunogenicity of live vaccines given after SOT and expert guidelines have been developed for select kidney and liver transplant recipients (12). Live vaccines can considered in individuals who are clinically well, at least 1 year post-transplant without concern for rejection, on low-level immune suppression, and meet minimum immune criteria (12). If the individual in case 2 had normal immune parameters, Varicella and then MMR vaccines could be offered to the family. Results from a multicenter study containing 281 pediatric kidney and liver transplant recipients who received Varicella or MMR vaccines found live vaccines to be both safe and immunogenic (37).

While significant advances have been made in the field, uncertainty remains about optimal timing, durability of immune responses post-transplant and need for booster doses, and the safety and immunogenicity of new vaccines (38). In addition, the approach to live vaccines both pre and post-transplant is variable across institutions and warrants further study. In a small case series of 5 pediatric heart and liver recipients who received live vaccines 8–21 days prior to transplant, none developed vaccine-related adverse events or concern for viral illness (39). This suggests that a shorter interval may be safe, and transplant should not be delayed if live vaccines are inadvertently administered; although, it is important to note the sample size was small and four of the five individuals received post-exposure prophylaxis with IVIG and antiviral therapy.

There are a number of novel vaccine candidates in various stages of development, including candidates against respiratory syncytial virus (RSV) and cytomegalovirus. The first vaccine against RSV was recently approved by the US Food and Drug Administration for use in adults 60 years and older. RSV is a common cause of respiratory viral infections in infants and children and significant cause of severe infection in SOT recipients. There are a number of RSV vaccine candidates in late stages of clinical trials, and some already approved for pregnant women and the elderly with the hope for future trials in immunocompromised individuals.