Immunizations in hematopoietic cell transplant candidates and recipients

INTRODUCTION — Prevention of infection is of paramount importance to the ever-increasing population of patients who have impaired immunity, such as those who have undergone hematopoietic cell transplantation (HCT). Infection in these patients often results in excessive morbidity and mortality, and antimicrobial therapy is typically less effective than in the immunocompetent host [1]. Although immunization appears to be an obvious way to prevent infection, many patients with impaired immunity are unable to mount a protective immune response to active vaccination. Furthermore, immunization with live virus vaccines may result in unchecked proliferation of attenuated strains.

The rationale for immunizing patients who have undergone HCT will be reviewed here. Issues related to immunizations in patients who have had or are waiting for a solid organ transplant, who have undergone chemotherapy for treatment of hematologic malignancies or solid tumors, or who have other immunocompromising conditions, including human immunodeficiency virus (HIV) infection, and in healthy adults and health care workers are discussed separately. (See "Immunizations in solid organ transplant candidates and recipients" and "Immunizations in adults with cancer" and "Immunizations in persons with HIV" and "Standard immunizations for nonpregnant adults" and "Immunizations for health care providers".)

Other issues related to infections in HCT recipients are reviewed separately. (See "Evaluation for infection before hematopoietic cell transplantation" and "Overview of infections following hematopoietic cell transplantation" and "Prevention of infections in hematopoietic cell transplant recipients" and "Prevention of viral infections in hematopoietic cell transplant recipients" and "Prophylaxis of invasive fungal infections in adult hematopoietic cell transplant recipients" and "Prophylaxis of infection during chemotherapy-induced neutropenia in high-risk adults".)

RISK OF INFECTION — The risk of acquiring infection and the inability to prevent infection by immunization are directly related to the patient's "net state of immunosuppression" or severity of disease. The greater the degree of immunosuppression, the less likely the patient is to respond to immunization. Although certain vaccines provide some benefit to the immunocompromised patient, an adequate response cannot be assumed.

Successful protection of the immunocompromised adult may require the use of vaccines and/or passive immunization (ie, immune globulin) as well as adjunctive measures, such as antiviral drug prophylaxis during influenza A outbreaks. (See "Seasonal influenza in adults: Role of antiviral prophylaxis for prevention" and "Seasonal influenza in children: Prevention with antiviral drugs".)

The degree of immunosuppression after HCT varies with the type of transplant.

●After allogeneic HCT, the immune system of the recipient is replaced by the immune system of the donor. The factors contributing to the patient's "net state of immunosuppression" are the conditioning regimen for HCT, the presence of graft-versus-host disease, and the immunosuppressive agents administered after transplantation.

●Since there is no immunologic disparity between graft and host after autologous HCT, the factors contributing to the "net state of immunosuppression" are the high-dose chemotherapy and radiotherapy administered before transplantation as well as the underlying disease. The risk of infection for autologous HCT recipients may also relate to the cumulative effects of pretransplant immunosuppression, including such medications as rituximab and fludarabine, administered as therapy for the underlying malignancy before HCT.

Both autologous and allogeneic HCT recipients are at risk of developing infectious complications during the period of immune reconstitution. Both types of HCT recipients initially have profound humoral and cell-mediated immunodeficiency but gradually recover to the point of being capable of functional B and T cell responses [2]. Although controversial, CD4 count recovery provides a reasonable guide to immune system recovery [3-5].

The challenge is to maintain protective immunity through this period of profound immunosuppression when the recipient is unable to respond to immunization. Strategies focus on transferring, maintaining, and eventually eliciting protective immunity.

Surveys performed in Europe and the United States have shown that immunization practices after HCT vary widely [6,7]. In an attempt to standardize prophylactic strategies in HCT recipients, international guidelines were published in 2009 that include recommendations for immunizations [2].

GUIDELINES — In 2009, guidelines for preventing infectious complications after HCT were published, which represent the collaboration of several organizations from Europe and North America, including the European Blood and Marrow Transplant Group, the American Society of Blood and Marrow Transplantation, the Canadian Blood and Marrow Transplant Group, the Infectious Diseases Society of America (IDSA), and the United States Centers for Disease Control and Prevention (CDC) [2].

Although the 2009 guidelines make recommendations regarding the optimal time to initiate each of the vaccine series following HCT, no recommendations were made regarding dosing intervals when more than one dose is required, given the lack of data regarding this issue [2]. However, European guidelines from 2005 made recommendations regarding dosing intervals; we have followed these recommendations where relevant [8]. In 2013, the IDSA published guidelines for vaccination of immunocompromised hosts, including HCT recipients (table 1) [9]. Our recommendations are generally in keeping with these various guidelines.

These recommendations are based largely upon small studies of transplant recipients or information extrapolated from healthy individuals when no information is available in HCT recipients. It is well recognized that vaccine responses vary by type of HCT (eg, allogeneic, autologous, umbilical cord blood, reduced intensity), but there are insufficient data to make separate recommendations for each type.

APPROACH TO IMMUNIZATION

Pretransplant — Prior to HCT, HCT candidates who are not already immunocompromised should receive the vaccines that are indicated for immunocompetent individuals based upon age, vaccination history, and exposure history [9]. HCT candidates should receive live virus vaccines ≥4 weeks prior to the initiation of the conditioning regimen and inactivated vaccines ≥2 weeks prior to the initiation of the conditioning regimen.

Nonimmune HCT candidates ≥12 months of age should receive the varicella vaccine (a live virus vaccine) if they are not immunocompromised and if the interval until initiating the conditioning regimen is ≥4 weeks [9]. If there is sufficient time prior to HCT, two doses of the varicella vaccine should be given; for individuals 1 to 12 years of age, the doses should be separated by at least three months and, for individuals ≥13 years of age, the doses should be separated by at least four weeks.

Vaccination of patients with cancer and routine vaccination of healthy individuals are discussed in detail separately. (See "Immunizations in adults with cancer" and "Standard immunizations for nonpregnant adults" and "Standard immunizations for children and adolescents: Overview", section on 'Routine schedule'.)

Donor vaccination is discussed below. (See 'Donor vaccination' below.)

Post-transplant — HCT recipients should be immunized against a number of pathogens such as pneumococcus, Haemophilus influenzae, tetanus, and others once they are likely to mount an immune response. Most live virus vaccines are avoided altogether during the first 24 months following HCT. However, certain ones (eg, measles, mumps, and rubella vaccine) are indicated 24 months following HCT in patients who do not have active graft-versus-host disease and who are not receiving immunosuppressive agents [2,9]. The approach to immunization is summarized in the following table (table 1). Specific recommendations for each vaccine are presented below.

INACTIVATED VACCINES

Tetanus, diphtheria, and pertussis — The 2013 Infectious Diseases of America (IDSA) guidelines for vaccination of the immunocompromised host makes the following recommendations for vaccination of HCT recipients against tetanus, diphtheria, and pertussis; we agree with these recommendations (table 1) [9]:

●Three doses of tetanus- and diphtheria-containing vaccine should be administered six months following HCT.

•For children <7 years of age, three doses of DTaP should be administered.

•For patients ≥7 years of age, administration of three doses of DTaP may be given. Alternatively, a dose of Tdap should be administered, followed by either two doses of DT or two doses of Td.

DT contains full doses of both diphtheria toxoid and tetanus toxoid, whereas Td contains a full dose of tetanus toxoid and a reduced dose of diphtheria toxoid. In the United States, DT and DTaP are not approved by the US Food and Drug Administration for individuals >6 years due to adverse effects [9]. However, a study in adult HCT recipients suggests that such individuals have a lower risk of adverse effects with DT administration compared with immunocompetent adults [10]. It is not known whether the immune response to Td is equivalent to the response to DT. There are also data suggesting that the response to Tdap is poor in autologous HCT recipients [11], suggesting that it should be used as a booster rather than as part of the primary series. For this reason, the IDSA states that a three-dose series of DTaP should be considered for initial vaccination following HCT regardless of patient age [9].

The 2005 European recommendations suggest that doses should be spaced one to three months apart [8]. After the post-transplant series, tetanus and diphtheria booster vaccines can be administered according to routine recommendations for adults and children.

If Td is administered in an individual expected to be at increased risk for diphtheria infection, it is reasonable to check diphtheria titers following vaccination [2]. (See 'Serologic testing' below.)

Tetanus and diphtheria are rare in the developed world. However, tetanus remains common in the developing world and sporadic cases continue to occur in developed countries. Large epidemics of diphtheria have occurred in states of the former Soviet Union, and the disease remains endemic in parts of the developing world. The incidence of pertussis has been increasing in the United States and worldwide due largely to waning immunity among adolescents and adults (figure 1). HCT recipients are particularly vulnerable to pertussis infection because of pulmonary damage due to chemotherapy and/or total body irradiation. In one study, only 13.5 percent of HCT recipients had protective titers against pertussis after transplantation and only 2 of the 28 patients developed a twofold or greater response to vaccination with Tdap [10]. (See "Tetanus" and "Epidemiology and pathophysiology of diphtheria" and "Pertussis infection: Epidemiology, microbiology, and pathogenesis".)

A significant proportion of HCT recipients lack immunity to tetanus, diphtheria, and pertussis after transplantation [10-14]. Titers of both tetanus and diphtheria antibodies vary by age at transplantation, underlying diagnosis, dose intensity, duration of treatment before transplantation, and the transplantation conditioning regimen. Approximately 50 percent of allogeneic HCT recipients and 19 percent of autologous HCT recipients who had protective levels of tetanus antibody before transplantation become seronegative within one year of transplantation [12,13]. Only 36 percent of HCT recipients retain immunity to diphtheria [15].

Vaccination against tetanus, diphtheria, and pertussis is discussed in greater detail separately. (See "Diphtheria, tetanus, and pertussis immunization in children 6 weeks through 6 years of age" and "Diphtheria, tetanus, and pertussis immunization in children 7 through 18 years of age" and "Pertussis infection in adolescents and adults: Treatment and prevention", section on 'Vaccination' and "Tetanus-diphtheria toxoid vaccination in adults".)

Poliovirus — The inactivated poliovirus vaccination is recommended for all HCT recipients. The vaccine is given as a three-dose series and should be initiated 6 to 12 months following transplantation (table 1) [2,9]. The doses can be administered one to three months apart [8]. The live oral poliovirus vaccine should not be given to HCT recipients, their household contacts, or their health care providers. (See "Poliovirus vaccination".)

Approximately 33 percent of allogeneic HCT recipients lose protective antibody to all three poliovirus vaccine types two to three years after transplantation [16], whereas 20 percent of autologous transplant recipients become seronegative to at least one poliovirus vaccine type within the first transplant year [17]. In different studies, the inactivated poliovirus vaccine was moderately to highly immunogenic among HCT recipients [16,18].

Encapsulated bacteria — After the first six months following transplantation, HCT recipients are at increased risk for invasive disease from encapsulated bacteria such as Streptococcus pneumoniae and Haemophilus influenzae type b (Hib) [19-27]. The risk is higher for allogeneic than autologous transplant recipients [25], and it is highest among allogeneic transplant recipients with graft-versus-host disease (GVHD) [21-23]. Invasive pneumococcal infection occurs in 3.8 per 1000 autologous HCT recipients, 8.23 per 1000 allogeneic HCT recipients, and in 20.8 per 1000 with chronic GVHD [28]. The incidence of Hib infections is less well established in HCT recipients, although fatal infections due to this pathogen are rare. (See "Overview of infections following hematopoietic cell transplantation".)

The increased susceptibility to these organisms is caused by low serum anticapsular antibody concentrations following transplantation [23,26]. In one study, for example, less than 30 percent of HCT recipients had protective antibodies against Hib one year after transplantation [27]. Immunization with all unconjugated polysaccharide vaccines (pneumococcus, Hib, and meningococcus) does not increase anticapsular polysaccharide antibody concentrations because HCT recipients respond poorly to T cell-independent polysaccharide antigens [26,29].

Fortunately, the polysaccharide-conjugate vaccines against H. influenzae and S. pneumoniae are promising alternatives to the unconjugated vaccines in HCT recipients [30].

Pneumococcus — For HCT recipients, we suggest giving three doses of a pneumococcal conjugate vaccine at one-month intervals starting three to six months following transplantation (table 1) [2,9]. The 20-valent pneumococcal conjugate vaccine (PCV20) is preferred because it covers the most serotypes, but the 15-valent pneumococcal conjugate vaccine (PCV15) or 13-valent pneumococcal conjugate vaccine (PCV13) are reasonable alternatives if PCV20 is not available. At 12 months following HCT in patients without chronic GVHD, we administer a single dose of the polysaccharide pneumococcal vaccine (PPSV23) to those who have received the 10-valent pneumococcal conjugate vaccine (PCV10), PCV13, or PCV15 in an attempt to broaden the immune response [9]. For those who are able to receive PCV20, PPSV23 is no longer recommended. For patients with GVHD, we administer a fourth dose of a pneumococcal conjugate vaccine at 12 months following HCT instead of PPSV23 since such patients respond particularly poorly to polysaccharide antigens.

PCV15 and PCV20 are pneumococcal conjugate vaccines that are protective against additional pneumococcal serotypes compared with PCV13. Pneumococcal conjugate vaccines that contain a different number of serotypes (eg, PCV10) are used in some countries in Europe and elsewhere. Patients should be vaccinated against pneumococcus according to their national guidelines.

We suggest serologic testing for pneumococcal serotypes one month or later following the third or fourth dose of PCV [2]. We test for antibodies against the serotypes included in the Quest multi-analyte immunodetection (MAID) test even though precise cut points for protective antibody titers are not clear. The serotypes antibodies included in MAID do not match perfectly with invasive pneumococcal disease isolates in HCT recipients [31]. The Quest MAID test includes the majority of serotypes found in PCV13, PCV15, and PCV20 (table 2), with the exception of 6A and 9V. The most common serotypes causing invasive pneumococcal disease include 6C, 10A, 15A, 19A, 19F, and 23F, all of which are included in the Quest MAID serotype antibody test except for 15A [31-33]. However, it is unclear which of the available methods for serologic testing is optimal and there is no accepted definition of an adequate serologic response. The European 2005 guidelines suggest testing for pneumococcal immunity every two to three years in patients with chronic GVHD and revaccinate those lacking immunity [8]. (See "Assessing antibody function as part of an immunologic evaluation".)

Inducing immunity against pneumococcus is challenging in HCT recipients because the PPSV23 is poorly immunogenic in this population, whereas pneumococcal conjugate vaccines (eg, PCV13, PCV15, PCV20) are more immunogenic but cover fewer serotypes. As an example, in one open-label study, 251 allogeneic HCT recipients received three doses of PCV13 at one-month intervals starting three to six months post-transplant, a fourth dose six months later, and one dose of PPSV23 one month after that [34]. Geometric mean fold rises of IgG geometric mean concentrations increased significantly from baseline to one month after the third dose of PCV13 for all PCV13 serotypes but declined over the following six months. An increase in antibody titers was seen again one month after the fourth dose of PCV13. There was little change following PPSV23 administration. The fourth dose of PCV13 was associated with increased local and systemic reactogenicity, but the overall safety profile was considered acceptable. In another trial of 64 pairs of HCT donors and recipients who were randomized to receive either the 7-valent pneumococcal conjugate vaccine (PCV7) or PPSV23 (donors vaccinated before transplantation and recipients vaccinated six months post-transplantation), a response to at least one serotype was seen in more patients receiving PCV7 compared with PPSV23 (39 versus 0 percent at 6 months, 91 versus 56 percent at 12 months) [35]. However, the overall immunogenicity of both vaccines was found to be poor; patients receiving PPSV23 responded to a mean of only 1.8 serotypes, whereas those receiving PCV7 responded to a mean of only 3.1 serotypes. Data on PCV15 and PCV20 efficacy in HCT recipients are limited.

Further discussion of pneumococcal vaccines is found elsewhere. (See "Pneumococcal vaccination in adults".)

Haemophilus influenzae — The Haemophilus influenzae type b (Hib) conjugate vaccine prevents invasive disease in infants and is recommended for routine childhood immunizations [36]. The Hib conjugate vaccine is well tolerated and immunogenic in HCT recipients [30,37,38].

HCT recipients should receive three doses of Hib conjugate vaccine starting 6 to 12 months following transplantation; at least four weeks should separate doses (table 1) [2,8,9,39].

Meningococcus — The target groups for meningococcal vaccination of HCT recipients are similar to those in the general population; HCT recipients who are at increased risk of meningococcal disease (eg, asplenic individuals, college students living in dormitories) should be vaccinated. When indicated, the meningococcal conjugate vaccine should be administered as a two-dose series 6 to 12 months following transplantation (table 3) [9,40]. Meningococcal vaccination (including indications, schedules, and need for revaccination) is discussed in detail separately.(See "Meningococcal vaccination in children and adults", section on 'Immunization of persons at increased risk'.)

Although there have been few studies evaluating the immunogenicity of meningococcal vaccination in HCT recipients [41,42], it is plausible that the conjugate vaccine is more immunogenic than the polysaccharide vaccine in this population since polysaccharide vaccines are known to generally be less immunogenic in HCT recipients than conjugate vaccines.

Influenza — Influenza vaccination remains the primary method for preventing influenza. Lifelong annual administration of the inactivated formulation of the influenza vaccine is recommended for all HCT candidates and recipients ≥6 months of age; vaccination should be given beginning six months following transplantation or beginning four months following transplantation if there is a community influenza outbreak (table 1) [9]. For those who were vaccinated less than six months following transplantation, a second dose should be considered [2]. Individuals <9 years of age who have not previously been vaccinated against influenza should receive two doses of the influenza vaccine, approximately one month apart. The live attenuated (intranasal) formulation should not be given to HCT recipients. (See "Seasonal influenza vaccination in adults" and 'Live virus vaccines' below and "Seasonal influenza in children: Prevention with vaccines", section on 'Target groups'.)

Adjunctive strategies for protection of HCT recipients involve immunizing close contacts and hospital staff as well as chemoprophylaxis of HCT recipients in some cases. (See 'Household contacts' below and "Seasonal influenza vaccination in adults" and "Infection control measures for prevention of seasonal influenza" and "Seasonal influenza in adults: Role of antiviral prophylaxis for prevention" and "Seasonal influenza in children: Prevention with vaccines", section on 'Target groups' and "Prevention of viral infections in hematopoietic cell transplant recipients", section on 'Chemoprophylaxis' and "Seasonal influenza in children: Prevention with antiviral drugs".)

Influenza A and B infections can be life-threatening in HCT recipients [43-46]. In one series, 5 to 6 percent of HCT recipients admitted with a respiratory illness had influenza and, in more than half, upper respiratory tract infection progressed to pneumonia (invasive influenza or secondary bacterial or fungal disease), resulting in a 50 percent mortality rate [46]. (See "Seasonal influenza in adults: Clinical manifestations and diagnosis".)

Vaccine-elicited antibody titers are lower early after HCT (during the first six months) and in patients with GVHD [47,48]. Nonetheless, some protection can be elicited. As an example, in a cohort study of 136 allogeneic HCT recipients, trivalent influenza vaccination was associated with a lower prevalence of influenza infection, slower progression to lower respiratory tract disease, and lower risk of hospitalization [49]. Compared with standard-dose trivalent inactivated vaccine, the high-dose vaccine elicited higher protective antibody titers in HCT recipients and was well tolerated except for injection-site reactions, which were mostly mild and resolved [50].

Timing of vaccine administration predicts the response. In one study, the response rate to influenza vaccine after HCT was zero if given in the first six months after transplant, 25 percent between months 6 and 24, and more than 60 percent after month 24 [51]. More recent data showed that influenza immunization at least six months after HCT was 80 percent effective in preventing influenza [52] and that influenza-specific T cell responses that might modify the course of infection could be elicited in patients vaccinated three to six months after HCT [53].

Hepatitis B — Hepatitis B is a well-recognized cause of morbidity and mortality in transplant recipients. However, the risk of acquiring hepatitis B after transplantation remains low unless the recipient has well-known risk factors, such as receiving hemodialysis.

We recommend a three-dose series of hepatitis B vaccine 6 to 12 months following HCT (table 1); we prefer to wait until 12 months when possible to optimize immunity from the vaccine [9]. Serologic testing to assess the response to hepatitis B vaccination is recommended ≥1 month following the third dose [2]. A second three-dose series is recommended in nonresponders (ie, those with anti-HBs concentrations <10 milli-international units [mIU]/mL). Among those receiving a second series, a high dose of the vaccine (40 mcg) should be given to adolescents and adults, whereas either the standard dose or the high dose can be given to children [2]. In those with an obvious reason for a poor response, such as chronic GVHD, it is preferable to wait until the underlying issue has improved.

For HCT recipients who are positive for hepatitis B core antibody (HBcAb), hepatitis B vaccination is particularly important because vaccination may reduce the risk of hepatitis B reactivation [2]. (See "Hepatitis B virus immunization in adults".)

Autologous HCT recipients immunized close to transplantation and allogeneic recipients immunized after transplantation with recombinant hepatitis B vaccine had variable and suboptimal responses [54,55]. In a study of 292 allogeneic transplant recipients not receiving immunosuppression and considered immune competent, 64 percent seroconverted following immunization with recombinant hepatitis B vaccine [56]. In a multivariate analysis, factors significantly associated with a poor immunologic response included age >18 years and previous chronic GVHD.

Hepatitis A — There are no data on the use of the hepatitis A vaccine in HCT recipients. Hepatitis A vaccination should be given according to the recommendations for the general population [2]. Patients with chronic liver disease (eg, GVHD, concurrent infection with other hepatitis viruses) may benefit from hepatitis A vaccine [57]. (See "Hepatitis A virus infection: Treatment and prevention".)

Indications for the use of hepatitis A immunoglobulin are discussed below. (See 'Hepatitis A immunoglobulin' below.)

Human papillomavirus — Vaccination against human papillomavirus can be considered in HCT recipients who have an indication based upon recommendations for the general population (table 1). Limited data suggest the quadrivalent vaccine is immunogenic following transplant [58]. (See "Human papillomavirus vaccination".)

COVID-19 vaccine — We agree with recommendations from United States Centers for Disease Control and Prevention Advisory Committee on Immunization Practices (ACIP) that all HCT candidates and recipients should receive coronavirus disease 2019 (COVID-19) vaccination [59]. For such patients, we suggest a messenger ribonucleic acid (mRNA) vaccine when available; if an mRNA vaccine is used, it is administered as a three-dose primary series for patients with moderate to severe immunocompromising conditions rather than the two-dose series used for the general population. Details on vaccination in HCT recipients is discussed below. Further discussion of COVID-19 vaccination prior to HCT is discussed elsewhere. (See "COVID-19: Considerations in patients with cancer", section on 'COVID-19 vaccination'.)  

●Individuals who were vaccinated prior to transplant − For patients who received a COVID-19 vaccine series prior to transplant, we agree with the ACIP recommendations to revaccinate with a full primary series at least three months after transplantation [59,60]. For mRNA vaccines, dosing intervals should follow the recommended schedule for each specific vaccine, with a third dose administered at least 28 days after the second dose. Although data on COVID-19 revaccination are lacking, loss of immunity to a variety of other infections after HCT suggests similar loss of immunity to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is likely.

●Unvaccinated transplant recipients − These patients should undergo COVID-19 vaccination at least three months after transplantation. If an mRNA vaccine is given, it is administered as a three-dose series in the following patients [59,60]:

•Patients who underwent HCT ≤2 years ago

•Patients who underwent allogeneic HCT and are actively taking immunosuppressive agents  

•Patients with a history of GVHD

•Patients who have another moderately or severely immunocompromising condition (table 4)

●Boosters for individuals vaccinated after transplant − Patients who have already received a primary series post-transplant should receive a booster. Details on booster dosing are discussed elsewhere. (See "COVID-19: Vaccines", section on 'Dose and interval (for immunocompetent individuals)'.)

We favor administration of an mRNA COVID-19 vaccine in HCT recipients, when available, because there is more evidence on the efficacy and safety of the vaccines in this population, including potential dosing adjustments to try to improve immunogenicity [61].

HCT recipients have a suboptimal immunogenic response after receiving the typical two-dose primary series of mRNA vaccines [62,63]. Administration of a third dose of an mRNA vaccine increases the likelihood of patients achieving a protective antibody response to COVID-19 [64,65]. In an open-label study of 88 allogeneic HCT recipients who received two doses of the BNT162b2 mRNA vaccine, 59 percent of individuals had anti-SARS-CoV-2 immunoglobulin (Ig)G titers indicative of vaccine protection [62]. Receipt of systemic immunosuppressive agents within the past three months and an absolute lymphocyte count <1000 cells/microL were associated with suboptimal antibody response. There were no cases of symptomatic COVID-19 detected at 84 days of follow-up. In another study of 42 patients who received an allogeneic HCT at least three months previously, did not achieve a protective antibody response after the second dose of BNT162b2 mRNA vaccine, and proceeded to receive a third dose, 48 percent developed a protective immunogenic response [64].

COVID-19 mRNA vaccines appear to be safe in HCT recipients >3 months post-transplant. However, cytopenias and cases of GVHD can occur. In a single-center prospective study of 66 allogeneic HCT recipients (with median time post-transplant of 32 months) who received the two-dose series of BNT162b2 mRNA vaccine, 5 percent developed GVHD within a week of each vaccine dose; all cases were controlled with immunosuppressants [66].

There is a rare risk for myopericarditis in adolescent and young adult patients that usually occurs after receiving the second dose of an mRNA vaccine. It is unknown whether patients receiving cardiotoxic chemotherapeutics (eg, anthracyclines) or additional mRNA vaccine doses are at greater risk for cardiotoxicity [67]. (See "COVID-19: Vaccines", section on 'Myocarditis'.)

Detail on COVID-19 vaccines and vaccine recommendations and timing for HCT candidates is discussed separately. (See "COVID-19: Vaccines" and "COVID-19: Considerations in patients with cancer", section on 'COVID-19 vaccination'.)

ZOSTER VACCINE — We suggest vaccination against herpes zoster (shingles) in HCT recipients ≥18 years of age with recombinant (nonlive) zoster vaccine (RZV) if they have not already received it [68]. Timing of administration depends on whether the patient received an autologous or an allogeneic HCT. The live attenuated zoster vaccine is not recommended. Further information on the differences between the two zoster vaccines and administration pretransplant in patients with hematologic malignancies is discussed separately. (See "Vaccination for the prevention of shingles (herpes zoster)" and "Immunizations in adults with cancer".)

●Autologous HCT recipients – In autologous HCT recipients, we administer the first dose 50 to 70 days following transplant and the second dose one to two months later.  

Our recommendations are based on the results of a large international multicenter observer-blinded phase III trial in which 1846 adult autologous HCT recipients were randomly assigned to receive two doses of RZV or placebo 50 to 70 days following HCT and one to two months later [69]. After a median of 21 months of follow-up, the vaccinated group had a lower incidence of herpes zoster compared with the placebo group (incidence 30 and 94 per 1000 person-years, respectively; incidence rate ratio [IRR] 0.32, 95% CI 0.22-0.44; 68.2 percent vaccine efficacy). Vaccination was also associated with a reduction in postherpetic neuralgia (IRR 0.11, 95% CI 0.00-0.78), other herpes zoster-associated complications (IRR 0.22, 95% CI 0.04-0.81), herpes zoster-associated hospitalization (hazard ratio [HR] 0.15, 95% CI 0.03-0.68), and duration of severe worst herpes zoster-associated pain (HR 0.62, 95% CI 0.42-0.89). Injection site reactions were reported in 86 percent of vaccine recipients and 10 percent of placebo recipients. Unsolicited and serious adverse effects, potentially immune-mediated diseases, and underlying disease relapses were similar between groups. Because of concerns of immunogenicity from the novel adjuvant contained in RZV, development of immune-mediated diseases was monitored in the trial. During the year following the second dose, 13 vaccine recipients and 8 placebo recipients reported at least one potentially immune-mediated disease; this difference was not statistically significant. The most frequently reported events in vaccine recipients were psoriasis and interstitial lung disease (in two vaccine recipients for each event).

In a large international multicenter phase III trial, a different type of inactivated zoster vaccine (an investigational gamma-irradiated vaccine) administered in four doses (one before autologous HCT and three post-HCT) was safe, immunogenic, and effective at reducing the incidence of herpes zoster and its complications when compared with placebo [70]. This vaccine is not expected to be available.

●Allogeneic HCT recipients – In allogeneic HCT recipients, we avoid adjuvanted vaccines, such as the recombinant zoster vaccine, until the patient meets the following criteria:

•At least 24 months has passed since HCT

•At least eight months off immunosuppressive therapy

•No recent graft-versus-host disease (GVHD) flares  

We administer RZV to those who meet the criteria, with the second dose administered at least two months after the first dose.

Data on the efficacy and safety of RZV in allogeneic HCT recipients are scarce. In one single-center prospective cohort study of allogeneic HCT recipients on antiviral prophylaxis (30 percent with acute GVHD at time of vaccination) who received the first dose of RZV between 9 to 24 months post-HCT and the second dose at least two months later, there was no difference in GVHD incidence post-vaccination compared with the incidence rate in unvaccinated HCT recipients [71]. Of the 34 patients who discontinued antiviral prophylaxis during the study follow-up, four developed HZ with one fatal case. Although the data are promising, further studies are needed prior to recommending RZV vaccination earlier post-HCT.

Postmarketing safety data will be important to assess whether there are long-term safety issues. Also, the duration of protection more than two years after HCT will require further assessment.

LIVE VIRUS VACCINES — Live virus vaccines are generally avoided in HCT recipients, particularly during the early post-transplant period, although certain vaccines (measles, mumps, and rubella [MMR]; varicella) are indicated under some circumstances. Live virus vaccines should be avoided in HCT recipients with active graft-versus-host disease (GVHD) and/or ongoing immunosuppression [9].

A list of live vaccines is provided in the following table (table 5).

Measles, mumps, and rubella — Although measles, mumps, and rubella are vaccine-preventable diseases, outbreaks of measles and mumps continue to occur due to incomplete vaccination of the population. Measles can cause severe disease in immunocompromised patients as evidenced by an epidemic in HCT recipients that occurred in Brazil [72]. In addition, protection against rubella is important for female patients who may become pregnant. (See "Measles: Clinical manifestations, diagnosis, treatment, and prevention" and "Mumps" and "Rubella".)

Optimizing immunity to measles, mumps, and rubella in HCT populations include checking serology in select patients and immunizing those who are seronegative at a safe interval after transplant:

●Check serology in select patients − Titers for measles, mumps, and rubella should be checked after HCT in:

•Pediatric patients

•Adults who received the MMR vaccine while immunosuppressed or six to eight weeks prior to the initiation of immunosuppression

•Women who may become pregnant

For those who were vaccinated prior to transplant, antibody titers to measles, mumps, and rubella decrease over time in HCT recipients [73-75]. In one report, for example, 24, 49, and 58 percent of allogeneic HCT recipients had lost antibody to measles, mumps, and rubella, respectively, one to two years after transplantation [73]. Women who had natural infection are much less likely to become seronegative after transplant than those who were previously immunized with MMR.

●Immunize seronegative patients − A two-dose series of the MMR vaccine should be administered to all measles and rubella seronegative pediatric and adult HCT recipients who meet all of the following criteria (table 1) [2,9]:

•24 months has passed since transplantation

•Recipient does not have active GVHD

•Recipient is not receiving any immunosuppression

•Last dose of intravenous immunoglobulin (IVIG) was administered more than 8 to 11 months ago

MMR appears to be safe and effective in both autologous and allogeneic HCT recipients [30,73,76]. In a study of 38 pediatric autologous or allogeneic HCT recipients, all patients developed protective antibodies to measles following vaccination [30]. Although MMR is safe for HCT recipients who are at least two years out from transplant and are not receiving immunosuppression, rare cases of vaccine-associated measles among HCT recipients have been reported [77].

Varicella — The varicella vaccine is a live attenuated vaccine that prevents chickenpox [2]. The live attenuated varicella vaccine can be used in HCT recipients with indications for varicella vaccination who meet the criteria listed below. In contrast, the live attenuated zoster vaccine is not recommended, due to its much higher viral titers compared with varicella vaccine.

In accordance with the Infectious Diseases Society of America (IDSA), we suggest that two doses of the live attenuated varicella vaccine be administered to varicella-seronegative HCT recipients who do not have active GVHD and are not receiving immunosuppression; the vaccine should be given ≥24 months following transplantation and 8 to 11 months after the last dose of IVIG (if applicable), whichever is later [9]. The recommended minimum interval between the first dose and the "catch-up" second dose of the live attenuated varicella vaccine is three months for children aged <12 years and four weeks for persons aged >13 years [78]. In contrast with the IDSA guidelines, the 2009 international guidelines consider the live attenuated varicella vaccine optional for such patients [2].

The safety and efficacy of live attenuated varicella vaccine, either before or after transplantation, are not well established. The live attenuated varicella vaccine was evaluated in 15 pediatric HCT recipients immunized 12 to 23 months after autologous or allogeneic transplant [79]. The vaccine was well tolerated and humoral immune responses were elicited in eight of nine patients, with persistence of responses in six patients after two years.

A case of disseminated fatal infection due to the vaccine strain of varicella was reported in an adult with recurrent diffuse large B cell lymphoma who was vaccinated with the live attenuated varicella vaccine four years following autologous HCT; the patient had not received chemotherapy for several years but had new diffuse large B cell lymphoma in abdominal lymph nodes [80]. Death from the vaccine strain of varicella is extremely rare.

CONTRAINDICATED VACCINES — Some vaccines are contraindicated in HCT due to safety concerns, particularly live virus vaccines and/or those that lack efficacy data. The following vaccines are contraindicated in HCT recipients: Bacillus Calmette-Guérin, oral poliovirus vaccine, intranasal influenza vaccine, cholera vaccine, oral typhoid vaccine, zoster vaccine, and rotavirus vaccine [2,9].

The live virus vaccines that are indicated following HCT (eg, measles, mumps, and rubella; varicella) must be given only to those who meet specific criteria for timing and/or immune function. (See 'Measles, mumps, and rubella' above and 'Varicella' above.)

PASSIVE IMMUNIZATION

Varicella — Varicella-seronegative HCT recipients who were transplanted within the previous 24 months, as well as those requiring immunosuppression or having chronic graft-versus-host disease, should be given varicella-zoster immune globulin (VariZIG) within 10 days of close or household contact with a person with either chickenpox or shingles [2,81]. In addition, seronegative patients undergoing conditioning for HCT who are exposed to an individual who has a varicella-like rash following varicella vaccination should receive VariZIG. Close contact for adults is defined as continuous household contact, hospital contact in the same two- to four-bed room, or prolonged face-to-face contact with an infectious staff member.

If VariZIG is not available, postexposure valacyclovir should be given [2]. HCT recipients who were seropositive prior to transplantation and who are highly immunosuppressed due to high-dose glucocorticoid therapy or a T cell-depleted allograft and who are exposed to an individual with chickenpox, shingles, or a post-vaccine varicella-like rash can also receive intravenous immunoglobulin (IVIG) or postexposure valacyclovir if VariZIG is not available.

Details regarding formulation and dosing of VariZIG and antivirals are discussed separately. (See "Post-exposure prophylaxis against varicella-zoster virus infection" and "Prevention of viral infections in hematopoietic cell transplant recipients", section on 'VZV postexposure prophylaxis'.)

Hepatitis A immunoglobulin — Hepatitis A-susceptible HCT recipients who anticipate possible exposure to hepatitis A (eg, during travel to endemic regions) or who have a known exposure should receive hepatitis A immunoglobulin (figure 2) [2]. (See "Hepatitis A virus infection: Treatment and prevention".)

IVIG following measles exposure — The 2013 United States Advisory Committee on Immunization Practices recommendations state that severely immunocompromised patients exposed to measles should receive intravenous immunoglobulin at a dose of 400 mg/kg regardless of vaccination or immunologic status [82]. Severely immunocompromised patients include those who have undergone HCT until at least 12 months after completion of immunosuppressive therapy, including therapy for graft-versus-host disease. (See "Measles, mumps, and rubella immunization in adults", section on 'Post-exposure prophylaxis'.)

Intravenous immunoglobulin for other indications — Although the rationale for considering passive antibody immunotherapy may be clear, the cost-effectiveness of using immune globulin preparations for the prevention of infections other than varicella, hepatitis A, and measles continues to be intensely debated and investigated. The possible use of intravenous immunoglobulin and cytomegalovirus-specific immune globulin are discussed elsewhere. (See "Prevention of infections in hematopoietic cell transplant recipients", section on 'Intravenous immune globulin'.)

Respiratory syncytial virus — Respiratory syncytial virus (RSV) is a serious cause of pneumonitis in HCT recipients that tends to occur in outbreaks; mortality rates are between 15 and 70 percent in cohorts with and without treatment [83-87]. Palivizumab is a humanized monoclonal antibody against the RSV F glycoprotein that is used by some HCT centers in HCT recipients <4 years of age as prophylaxis monthly during RSV season (November through April in the northern hemisphere) to prevent primary RSV pneumonitis [2], although this practice is not supported by clinical trials. (See "Respiratory syncytial virus infection: Prevention in infants and children".)

SEROLOGIC TESTING — Serologic testing is recommended prior to measles and varicella vaccination in HCT recipients, and vaccination against these viruses should only be performed in individuals who are seronegative [2]. Although the 2009 international guidelines do not address rubella specifically, we suggest that the same approach be used for rubella. Serologic testing following vaccination is recommended after pneumococcal and hepatitis B vaccination to document an adequate response.

Periodic testing is also recommended in HCT recipients to assess for the maintenance of antibody responses [2]. Testing should be repeated approximately every four to five years to assess immunity to hepatitis B, measles, tetanus, diphtheria, and poliovirus. Testing for immunity to pneumococcus should also be considered every two years for the first four years after transplantation.

DONOR VACCINATION — The optimal timing of immunization following HCT requires a balance between the ability to induce adequate immune responses, which increases over time, and the importance of providing protection during the highest risk period. As an example, the median time for developing invasive pneumococcal and Haemophilus influenzae type b (Hib) disease was about nine months after transplantation in one study [88].

One possible approach to protection of HCT recipients from vaccine-preventable disease early after transplant before the HCT recipient can achieve an adequate immune response to immunizations involves vaccinating the donor prior to stem cell harvest. Although donor immunization can be done prior to stem cell harvesting when the donor is related to the recipient and agrees to being vaccinated in order to enhance the immune responses of the recipient, the 2009 international guidelines regarding immunization of HCT recipients do not make a recommendation regarding donor vaccination due to practical and ethical challenges [2]. The 2013 Infectious Diseases Society of America guidelines recommend against vaccinating the donor solely for the benefit of the recipient [9]. We agree with these recommendations.

The possible benefit to HCT recipients of vaccinating donors has been shown in studies with Pseudomonas aeruginosa polysaccharide conjugate vaccine, diphtheria and tetanus toxoid vaccines, and hepatitis B vaccine: adoptive transfer of specific antibodies was achieved from immunized HCT donors to both non-T cell- and T cell-depleted allogeneic HCT recipients [89-93]. In one report, for example, donors immunized with tetanus toxoid shortly before stem cell collection transferred a larger and more diverse tetanus toxoid-specific T cell repertoire to the recipient, indicating that donor immunization allows adoptive transfer of both B cells actively synthesizing antibody as well as antigen-specific T cells [92].

Donor immunizations with tetanus toxoid, diphtheria toxoid, Haemophilus influenzae B conjugate vaccine, and pneumococcal conjugate vaccine have been shown to improve immunity in HCT recipients [93-96]. As an example, donor immunization with Hib conjugate vaccine resulted in significantly higher antibody concentrations in recipients of non-T cell-depleted allogeneic transplants as early as three months post-transplant compared with recipients of unimmunized donors [93]. However, although this strategy may be effective, it is unlikely to be cost effective for the prevention of invasive Hib disease in HCT recipients.

The ability of donor immunization with pneumococcal conjugate vaccines to enhance early protective antibody response was observed in HCT recipients whose donors were randomly assigned to receive either a dose of the 7-valent pneumococcal conjugate vaccine (PCV7) or no vaccine before transplantation [95]. Following transplantation, all HCT recipients received PCV7 at 3, 6, and 12 months. After the first dose of vaccine, 76 percent of HCT recipients in the immunized donor group had protective antibody concentrations to all seven serotypes compared with 36 percent in the unimmunized donor group. This strategy may prove to be cost effective since pneumococcal infections are more common than Hib infections during the first transplant year.

There are case reports of attempts to clear chronically infected HCT recipients by immunizing the donor with hepatitis B vaccine and immunizing the recipient with hepatitis B vaccine in the early post-transplant period [54,97].

HOUSEHOLD CONTACTS — Household contacts should receive recommended routine vaccinations. Household contacts with an indication for live vaccines should ideally receive them before HCT candidate undergoes transplantation provided there are no contraindications. (See "Standard immunizations for nonpregnant adults" and "Standard immunizations for children and adolescents: Overview", section on 'Routine schedule'.)

Under some circumstances, a household member may have received a live attenuated vaccine. The following precautions should be followed for preventing possible transmission of the attenuated vaccine virus to the HCT recipient when this situation arises:

●Influenza vaccine – Annual influenza vaccination is recommended for all family members and close or household contacts ≥6 months of age. Only the inactivated influenza vaccines (IIV) should be used among contacts of HCT recipients within two months of transplant and in HCT recipients with graft-versus-host disease (GVHD), cord blood transplant recipients, and recipients of T cell-depleted transplants. Either IIV or the live attenuated influenza vaccine (LAIV) may be given to contacts of HCT recipients who underwent transplantation >2 months earlier and who are not highly immunosuppressed, such as those without GVHD, recipients of non-cord blood transplants, and recipients of non-T cell-depleted transplants; LAIV can be used in healthy nonpregnant individuals between 2 and 49 years of age [9,98]. (See "Seasonal influenza vaccination in adults" and "Seasonal influenza in children: Prevention with vaccines", section on 'Target groups'.)

●Poliovirus vaccine – All household contacts with an indication for poliovirus vaccination should receive the inactivated poliovirus vaccine rather than the oral formulation, which is a live attenuated vaccine [2]. The oral polio vaccine is no longer available in the United States. If a household member inadvertently receives the oral formulation, close contact between the household member and the HCT recipient should be avoided for four to six weeks. If avoidance of close contact is not possible, then the HCT recipient should practice stringent hand hygiene after contact with the feces of the vaccinee (eg, after changing a diaper) and avoid contact with saliva from the vaccinee, including not sharing food or eating utensils. Infants and children who have recently received the oral poliovirus vaccine should not visit the HCT unit for four to six weeks after receipt of the vaccine. (See "Poliovirus vaccination".)

●Rotavirus vaccine – Two formulations of rotavirus vaccine, RV1 and RV5, are available. Both are live attenuated vaccines and are used in infants. Rotavirus vaccine should be given to infants who are household contacts of HCT recipients according to age-based recommendations [9]. (See "Rotavirus vaccines for infants", section on 'Routine schedule'.)

Although no cases of transmission of the attenuated vaccine virus have been reported, HCT recipients should avoid handling diapers of vaccinees for four weeks following vaccination [2,9]. When this is not possible, HCT recipients should adhere to strict hand hygiene practices after contact with the vaccinee's feces. Some HCT units prohibit infants who have received the rotavirus vaccine within the previous two to four weeks from visiting the HCT unit. (See "Rotavirus vaccines for infants", section on 'Shedding and transmission of vaccine virus'.)

●Zoster vaccine – The herpes zoster vaccine is recommended for adults ≥50 years of age in the United States and should be given to household contacts in this age group [9].

Although no cases of transmission of the attenuated vaccine virus have been reported, HCT centers should prohibit visitors who develop a varicella- or zoster-like rash following vaccination from visiting. If a household member develops such a rash after vaccination against herpes zoster, he or she should avoid close contact with the HCT recipient and should keep the rash covered. Management of HCT recipients who have been exposed to an individual with a zoster-like rash is discussed above. (See 'Varicella' above and "Vaccination for the prevention of shingles (herpes zoster)".)

●Varicella vaccine – Transmission of the live attenuated varicella vaccine virus has been reported very rarely [78]. Household members who have not had varicella infection should receive the varicella vaccine to protect the HCT recipient from potential exposure to wild-type virus [2,9]. We suggest that household contacts be vaccinated before HCT has occurred when feasible. Individuals who develop a varicella-like rash within one month of vaccination should be prohibited from visiting the HCT unit and should avoid close contact with the HCT recipient in the home setting. (See "Vaccination for the prevention of chickenpox (primary varicella infection)", section on 'Contacts of immunocompromised hosts'.)

●Measles, mumps, and rubella vaccine – Household members should receive the measles, mumps, and rubella vaccine as indicated by age [2,9]. Individuals who develop a fever and/or rash following vaccination should be prohibited from visiting the HCT until signs and symptoms have resolved and should avoid close contact with the HCT recipient in the home setting. (See "Measles, mumps, and rubella immunization in adults" and "Standard immunizations for children and adolescents: Overview", section on 'Routine schedule'.)

●Travel vaccines – Household contacts may receive the yellow fever vaccine and the oral typhoid vaccine if indicated for travel. (See "Immunizations for travel".)

TRAVELERS — Certain vaccines (rabies, tick-borne encephalitis, inactivated Japanese encephalitis, yellow fever) can be considered for travelers to endemic areas [2]. However, there are few data regarding the safety and efficacy of these vaccines in HCT recipients and the decision of whether to administer them should be based upon the individual patient's risk of infection and the potential adverse effects. Of these vaccines, only the yellow fever vaccine is a live virus vaccine; it should only be used in HCT recipients who underwent transplantation >24 months earlier, do not have active graft-versus-host disease, and are not receiving immunosuppression.

Immunizations in immunocompromised travelers are discussed in detail separately; the use of the different vaccines in HCT recipients must be considered in relation to the issues described in this topic. (See "Travel advice for immunocompromised hosts".)

SOCIETY GUIDELINE LINKS — Links to society and government-sponsored guidelines from selected countries and regions around the world are provided separately. (See "Society guideline links: Immunizations in hematopoietic cell transplant recipients".)

SUMMARY AND RECOMMENDATIONS

●Role of vaccines − Prevention of infection is of paramount importance to the ever-increasing population of patients who have impaired immunity, such as those who have undergone hematopoietic cell transplantation (HCT). Although immunization appears to be an obvious way to prevent infection, many patients with impaired immunity are unable to mount a protective immune response to active vaccination. Furthermore, immunization with live virus vaccines may result in unchecked proliferation of attenuated strains. (See 'Introduction' above.)

●Timing of vaccination post-transplant − Following transplantation, HCT recipients typically lose immunity to pathogens against which they were previously immunized. Thus, HCT recipients should be immunized against a number of pathogens such as pneumococcus, Haemophilus influenzae, tetanus, and others once they are likely to mount an immune response (table 1). Live virus vaccines are avoided altogether during the first 24 months following HCT. (See 'Post-transplant' above.)

●Choice of vaccines − We recommend using inactivated vaccines rather than live vaccines in HCT recipients when an inactivated formulation exists, such as with the zoster and influenza vaccines (Grade 1C). (See 'Live virus vaccines' above.)

●COVID-19 vaccine − For previously unvaccinated HCT recipients, we recommend vaccination against COVID-19 (Grade 1B). In such individual, we administer vaccine at least three months after transplantation. For HCT recipients who were vaccinated prior to transplantation, we suggest revaccination with a full COVID-19 vaccine series (Grade 2C), at least three months after transplantation. (See 'COVID-19 vaccine' above.)

●Zoster vaccine − We suggest vaccination with RZV in autologous HCT recipients ≥18 years of age, with the first dose given 50 to 70 days following transplant and a second dose given one to two months later (Grade 2B). We suggest vaccination with RZV beginning 24 months following transplantation in allogeneic HCT recipients ≥18 years of age who do not have active graft-versus-host disease and have not received immunosuppression for at least the last eight months (Grade 2C). The live attenuated zoster vaccine is contraindicated in HCT recipients. (See 'Zoster vaccine' above.)

●Measles, mumps, and rubella vaccine

•We suggest that the MMR vaccine be administered to all measles-seronegative pediatric and adult HCT recipients (Grade 2C). It should be given beginning 24 months following transplantation in patients who do not have active graft-versus-host disease and are not receiving immunosuppression. (See 'Measles, mumps, and rubella' above.)

•In women who are seronegative for rubella and who may become pregnant, we suggest vaccination against rubella with the MMR vaccine (Grade 2C). (See 'Measles, mumps, and rubella' above.)

●Varicella vaccine − We suggest live attenuated varicella vaccine for HCT recipients who are seronegative for varicella, but it should only be given ≥24 months following transplantation in patients who do not have active graft-versus-host disease and who are not receiving immunosuppression and 8 to 11 months after the last dose of IVIG (if applicable), whichever is later (Grade 2C). (See 'Varicella' above.)

●Vaccinations for travelers − Certain vaccines (rabies, tick-borne encephalitis, Japanese encephalitis, yellow fever) can be considered for travelers to endemic areas. However, there are few data regarding the safety and efficacy of these vaccines in HCT recipients and the decision of whether to administer them should be based upon the individual patient's risk of infection and the potential adverse effects. (See 'Travelers' above.)

●Role of passive immunization − Passive immunization is indicated in nonimmune HCT recipients under certain circumstances, such as following exposure to an individual with varicella, measles, or hepatitis A infection. (See 'Passive immunization' above.)

●Serologic testing − Serologic testing should be performed prior to measles, rubella, and varicella vaccination in HCT recipients. Serologic testing following vaccination is recommended after certain other vaccines to document an adequate response and/or assess for the maintenance of antibody responses over time. (See 'Serologic testing' above.)

●Vaccination of household contacts − Household contacts should receive recommended routine vaccinations. (See 'Household contacts' above.)