Abstract
The use of live attenuated vaccines in patients with immunosuppressive agents is contraindicated in package inserts and guidelines in Japan and other countries. However, patients receiving immunosuppressants have a high risk of infectious disease becoming severe, and the necessity to prevent infectious disease is high. To date, 2,091 vaccinations have been reported in 25 reports of live attenuated vaccines in people receiving immunosuppressants. Twenty-three patients (1.1%) became infected with the virus strain used in the vaccine, which was varicella virus in 21 patients. No reports have described life-threatening complications. A prospective study at the National Center for Child Health and Development conducted under certain immunological conditions (CD4 cell count ≥ 500/mm3, stimulation index of lymphocyte blast transformation by phytohemagglutinin (PHA) ≥ 101.6, serum immunoglobulin G ≥ 300 mg/dL) confirmed the serological effectiveness and safety. The evidence suggests that live attenuated vaccines can be used even in combination with immunosuppressants. Further evidence must be gathered and immunological criteria investigated to determine the conditions for safe use. Depending on the results of these investigations, the wording in package inserts and guidelines may need to be revised.
Similar content being viewed by others
Avoid common mistakes on your manuscript.
Introduction
In package inserts and various guidelines in both Japan and other countries, the use of live attenuated vaccines in patients with immunosuppressive agents is clearly contraindicated. However, as patients receiving immunosuppressants are at elevated risk of severe infectious disease, they need to prevent infectious disease more than healthy individuals. In current society, many clinicians struggle with the dilemma of the necessity of prevention of infection and being unable to vaccinate immunosuppressed individuals against measles and varicella. Discontinuing lifelong immunosuppressants is difficult in many patients after solid organ transplants or other conditions, and under current conditions these patients can never be vaccinated with live attenuated vaccines. This article presents an overview of the current state of evidence regarding live attenuated vaccination of patients receiving immunosuppressants, vaccination reports to date, problems faced in performing vaccinations, and the future outlook.
Infectious diseases for which live attenuated vaccines are needed for prevention
Infectious diseases for which live attenuated vaccines are needed for prevention include measles, rubella, varicella, mumps, rotavirus, yellow fever, and tuberculosis. The vaccination rate for the measles-rubella (MR) vaccine is very good in Japan, with more than 95% of the general population having completed the vaccination by 2 years old. Reports of measles patients have decreased with the rise in the vaccination rate in Japan, which was certified by the World Health Organization in 2015 as a country that has eliminated measles. However, reports of measles have not completely ceased, as imported cases are still encountered along with occasional epidemics. Major epidemics of rubella are also occasionally seen, and in epidemic years many reports describe patients with congenital rubella syndrome. In Japan, varicella became a target disease for routine vaccination in November 2014. Since then, the vaccination rate has risen each year, and currently more than about 95% of children have received at least one dose by age 2. Accordingly, the number of infections has decreased in recent years. Even so, epidemics of varicella are still sometimes seen. The mumps vaccine remains a voluntary vaccination and infections are frequently seen. Particularly when the disease is contracted in adults, problems such as orchitis in men are described.
Although the number of patients infected with measles, rubella, varicella, and mumps are tending to decrease compared to the past, epidemics sometimes occur even today. Patients receiving immunosuppressants who cannot be administered live attenuated vaccines are thus exposed to the risk of these infectious diseases.
Current status of live attenuated vaccines in people receiving immunosuppressants or steroids
The current status of live attenuated vaccines in people receiving immunosuppressants or steroids is summarized in Table 1. The package inserts and several guidelines in Japan and the United States show that live attenuated vaccines are generally contraindicated in patients with immunosuppressive agents, although varicella vaccine is relatively accepted if the immunosuppression is mild, as it was originally developed for immunocompromised individuals. The American Academy of Pediatrics’ Red Book 2021–2024, Infectious Diseases Society of America 2013 [1], Advisory Committee on Immunization Practices, and others also state that the use of live attenuated vaccines is contraindicated in patients receiving immunosuppressants.
Reasons for contraindicating live attenuated vaccines in patients receiving immunosuppressants
In patients with a highly suppressed immune status (particularly cellular immunodeficiency), development of fatal viral infections from the vaccine strain in the live attenuated vaccine is a known possibility. This includes miliary tuberculosis after BCG vaccination, life-threatening measles infection after measles vaccination, disseminated varicella after varicella vaccination, meningoencephalitis after mumps vaccination, paralysis after live polio vaccination, and intractable diarrhea after rotavirus vaccination. Live attenuated vaccines therefore cannot be used in patients with cellular immunodeficiency.
For reference, live attenuated vaccines are contraindicated for individuals with cellular and humoral immunodeficiency, such as severe combined immunodeficiency, Wiskott–Aldrich syndrome, and hyper-immunoglobulin (Ig)M syndromes, and humoral immunodeficiency such as X-linked agammaglobulinemia, but live attenuated vaccines except for BCG can be used for individuals with diseases that cause abnormalities in phagocytes (neutrophils, monocytes, macrophages), such as chronic granulomatous disease and congenital neutropenia. These vaccines can also be used in patients with disorders such as ataxia-telangiectasia, selective IgA deficiency, and complement deficiency. We should therefore be aware that it is not the case that live attenuated vaccines cannot be used in all immunodeficiencies, but they definitively cannot be used in patients with cellular immunodeficiencies and humoral immunodeficiencies.
Secondary infections from the vaccine strains have also been reported with varicella vaccines, mumps vaccines, rotavirus vaccines, live polio vaccines, and others. The incidences of varicella rash (or herpes zoster) from the vaccine strain after varicella vaccination and parotid swelling after mumps vaccination are very low, but cases have been reported even in previously healthy individuals, and multiple case reports have described secondary infections in siblings and others. However, since the viruses involved are attenuated, the disease does not become severe unless the individual is in an immunocompromised state. The rotavirus vaccine and live polio vaccine are known to be excreted in feces for a short time after inoculation in infants, and so should not be used if there is an immunocompromised person in the family. Inactivated polio vaccines have now been introduced in Japan and live vaccines are no longer used.
Given the above, live attenuated vaccines are indisputably contraindicated for individuals in a highly immunosuppressed state, particularly those with cellular immunodeficiency. Accordingly, package inserts for immunosuppressants contraindicate concurrent use with live attenuated vaccines. However, not all patients who are receiving immunosuppressants develop cellular immunodeficiency. Rather, the parameters of cellular immunity on blood tests are often mostly normal.
Risk of severe infection in patients receiving immunosuppressants
A large number of reports have described death from varicella in patients undergoing immunosuppressive therapy or immunocompromised patients (Table 2) [2,3,4,5,6,7,8,9,10,11,12,13,14]. Varicella is known to cause internal organ damage in an immunosuppressed state, and is sometimes complicated by multiple-organ failure. Our Center has also experienced a patient with multiple-organ failure from varicella who could not be saved. Depending on the report, the mortality rate is within a wide range of 0–80%. However, looking at the total for reports presented in this document, 23 deaths were identified among a total of 326 patients (mortality rate, 7.1%). This is very high compared with the 0.002–0.004% reported among healthy individuals. For measles, we were unable to find any case series with large numbers of patients receiving immunosuppressants, but the mortality rate from measles among immunocompromised patients is very high, at 20.0–83.3% [15,16,17,18,19], and all cases showed complicating pneumonia or encephalitis (mortality rate in healthy individuals, 0.1–0.3%). For mumps, reports have included death from meningoencephalitis in a patient with combined immunodeficiency after bone marrow transplantation [20]. Our responsibility is to protect children for whom there is no option but to receive immunosuppressants over the long term from these viral infections.
For patients with pre-existing conditions, the fact that contracting an infection can cause recurrence or exacerbation of the primary disease is also problematic. Infections triggering a recurrence of nephrotic syndrome, exacerbation of rheumatic diseases such as systemic lupus erythematosus, acute rejection following kidney transplants, or other problems, are not rare. Incidentally, two mechanisms are thought to be involved in these “recurrences” or “exacerbations” of primary disease triggered by infection: from immunological stimulation within the body from the infection, and from temporarily decreased doses or discontinuation of immunosuppressants following the development of an infection.
Reasons why the use of live attenuated vaccines is permanently difficult in patients receiving immunosuppressants
Steroid-resistant nephrotic syndrome and frequently relapsing nephrotic syndrome, both of which require the continuation of immunosuppressants, account for about 40% of all nephrotic syndromes and often occur at relatively young ages. These pathologies are also frequently experienced by patients who have not been vaccinated with live vaccines such as the combined measles-rubella vaccine or varicella vaccine. In nephrotic syndrome patients, repeated recurrence is common when immunosuppressants such as cyclosporine, MMF, and mizoribine are tapered or discontinued. Even if an immunosuppressant can be discontinued in these patients, live attenuated vaccines can no longer be used due to recurrence. Among recipients of solid organ transplants, all those in whom vaccination is possible are vaccinated before the transplant with a live vaccine, and transplantation is then performed after confirming a rise in antibodies. However, some cases cannot be administered a live attenuated vaccine in time, such as in liver transplants for fulminant liver failure during infancy. After the transplant, immunosuppressant therapy is continued for life, so live attenuated vaccines can never be used in the lifetime of that patient. Meanwhile, by continuing immunosuppressive therapy, it is not uncommon for antibodies to subsequently disappear, exposing the patient to a risk of viral infection.
To protect patients in whom discontinuation of such immunosuppressants is difficult from infection, the use of live attenuated vaccines is considered preferable during the time when the disease condition is stable under immunosuppressants. In fact, even when a patient is receiving immunosuppressants, a fair number of clinicians administer live attenuated vaccines after fully explaining to the family and patient that such use is technically contraindicated.
Reports in the literature on the use of live attenuated vaccines in patients receiving immunosuppressants
We identified 25 reports, including clinical research, case series, and case studies, on the use of live vaccines in patients receiving immunosuppressants [21,22,23,24,25,26,27,28,29,30,31,32,33,34,35,36,37,38,39,40,41,42,43,44,45]. Many of the patients involved had undergone solid organ transplants, and a large proportion were children (Table 3). A total of 2,091 vaccinations were administered (measles, n = 123; rubella, n = 82; varicella, n = 858; mumps, n = 418; yellow fever, n = 21; MR, n = 344; MMR, n = 244; measles-mumps-rubella-varicella (MMRV), n = 1) (Table 4). Adverse events were the development of vaccine-strain viral infections in 23 patients (1.1%). This included varicella rash after varicella vaccination or MMRV vaccination in 21 of 859 patients (2.4%), and parotid swelling after mumps in 2 of 418 mumps vaccination (2 of 663 vaccinations of mumps, MMR, or MMRV, 0.3%). The risk of vaccine-strain viral infections may be higher than in healthy individuals, but since the vaccines are attenuated, the infections seem milder than those from wild strains, and no life-threatening complications have been seen. Notably, nearly all viral infections from the vaccine strain have involved varicella, and not a single case of measles or rubella has been reported.
Prospective study of live attenuated vaccines in nephrotic syndrome patients receiving immunosuppressants
Here we describe the “Prospective study of live attenuated vaccines for patients with nephrotic syndrome receiving immunosuppressive agents” conducted from May 2011 to March 2018 at the National Center for Child Health and Development [36]. In this study, live attenuated vaccines were administered to patients with antibody titers of < 4.0 enzyme immunoassay (EIA)-IgG against measles, rubella, varicella, mumps or other diseases, pre-vaccination peripheral blood CD4+ T cells ≥ 500/mm3, stimulation index of lymphocyte blast transformation by phytohemagglutinin (PHA) ≥ 101.6, and serum IgG ≥ 300 mg/dL (Table 5). We never administer vaccinations in patients who are under B-cell depletion after rituximab treatment, as influenza and COVID-19 vaccination are reported ineffective during this period in patients with lymphoma and rheumatic diseases [46,47,48]. Antibody titers (mean ± standard deviation (SD)) at 2 months after single doses were measles 36.7 ± 72.6, rubella 29.8 ± 23.3, varicella 8.9 ± 11.9, and mumps 3.5 ± 3.5. Seroconversion rates were 95.7% for measles (22/23 vaccinations), 100.0% for rubella (19/19 vaccinations), 61.9% for varicella (26/42 vaccinations), and 40.0% for mumps (8/20 vaccinations). Patients with positive conversion were followed. After 1 year, antibodies were relatively well maintained for measles (15/18 patients, 83.3%), rubella (16/17 patients, 94.1%), and varicella (23/30 patients, 76.7%), although antibodies for mumps tended to decrease (2/10 patients, 20.0%). Patients with antibodies (EIA-IgG) ≥ 10.0 at 2 months were confirmed to have maintained long-term immunity. Among vaccinated patients who displayed positive conversion of antibodies, not a single breakthrough infection was seen. Adverse events included recurrence of nephrotic syndrome in 2 patients and several events including fever and rash for which the relationship to the vaccine was unclear, but no serious adverse events. Not a single case of vaccine-strain viral infection was identified. If certain immunological conditions are met, live attenuated vaccines have been confirmed to be safe and effective even in patients with nephrotic syndrome receiving immunosuppressants.
Prospective study of live attenuated vaccines in patients receiving immunosuppressants for conditions other than nephrotic syndrome
During the same period as the above study, we conducted another prospective study of live attenuated vaccines among patients receiving immunosuppressants for conditions other than nephrotic syndrome [42]. Two months after a single dose, the antibody titer (mean ± SD) was 34.3 ± 39.1 for measles, 55.0 ± 67.6 for rubella, 7.0 ± 6.8 for varicella, and 7.1 ± 7.1 for mumps. Seroconversion rates were 80.0% for measles (8/10 vaccinations), 100.0% for rubella (15/15 vaccinations), 59.1% for varicella (13/22 vaccinations), and 69.2% for mumps (9/13 vaccinations). These results were comparable to those of the study of patients with nephrotic syndrome receiving immunosuppressive agents [36]. In the present study, one person developed varicella from the vaccine strain after varicella vaccination, and was hospitalized for additional treatment. However, this patient was treated before the current immune criteria (Table 4) had been set, and presented with: CD4+ T cells, 511/mm3; stimulation index of lymphocyte blast transformation by PHA, 91.1; and serum IgG, 208 mg/dL. These findings would not meet the current criteria.
National survey on live attenuated vaccines in patients using immunosuppressive or biological agents
To enable the future use in society of live attenuated vaccines in patients receiving immunosuppressants, we conducted a national survey with the aim of revising the wording “contraindicated” on package inserts [44]. The primary survey was an institutional survey in which questionnaires were mailed to 480 institutions, receiving and analyzing responses from 415 institutions (86.5%). Of these, 13.8% of institutions administered live attenuated vaccines to patients receiving immunosuppressants, and 2.2% administered live attenuated vaccines to patients using biological agents. About two-thirds of institutions wanted to administer live attenuated vaccines even to patients receiving immunosuppressants. A secondary survey of patients was sent to 66 institutions, and information on 781 vaccinated patients was collected from 59 institutions (89.4%). Viral infections from the vaccine strain were seen in 2 patients (0.3%, both varicella), but no life-threatening adverse events were observed.
Current issues and future outlook for live attenuated vaccines in people receiving immunosuppressants
The prospective studies at our institution and past reports suggest the possibility that, under certain conditions, administration of live attenuated vaccines is safe and effective even in patients receiving immunosuppressants. However, patients receiving immunosuppressants include some with cellular immunodeficiency, who would thus face mortal danger from the high risk of vaccine-strain viral infections; in these patients, vaccination remains strictly contraindicated. Therefore, the immunological criteria enabling safe administration of vaccines among patients receiving immunosuppressants need to be investigated further.
Social adjustments also need to be made with the ultimate purpose of revising the descriptions in package inserts and guidelines for both immunosuppressants and live attenuated vaccines. Sharing information with related academic societies and experts and building a consensus, as well as maintaining close cooperation with the relevant regulatory authorities, will likely be necessary.
Conclusion
When vaccinating individuals with pre-existing conditions, the primary physician should always weigh the advantages and disadvantages when making vaccination decisions for individual patients. Factors for vaccination include a high risk to the patient in the event of contracting the disease the vaccine protects against (e.g., varicella in patients receiving immunosuppressants), a high risk of disease exacerbation with contraction of an infectious disease (e.g., recurrence of nephrosis after contracting influenza), and a high prophylactic effect from the vaccine. Factors against vaccination include the high frequency or risk of adverse reactions to the vaccine (which needs to be considered in individual patients), the high risk of vaccine-strain infection (e.g., live attenuated vaccines in patients with cellular immunodeficiency), the high risk of exacerbating pre-existing conditions with the vaccine, and the low prophylactic effect from the vaccine. These issues should not be decided uniformly, but instead need close consideration of the clinical course of the individual patient to date, their susceptibility to infection, the likelihood of adverse events after vaccination, and other factors.
Another important factor is the ratio of vaccinations in the general population. We should encourage healthy people to receive routine vaccinations thoroughly to protect immunocompromised patients from infectious diseases. In many countries, the system of routine vaccination is well developed and the vaccination rate is high, but there are many countries where the vaccination rate is low. Promotion and enlightenment of vaccination in healthy people might be crucial.
Finally, the relationships between the immune status of the patient and infection risk as well as the safety of live attenuated vaccines are shown in Fig. 1. The greater the decrease in immunity, the higher the risk of serious infection, which also makes administration of live attenuated vaccines difficult. For patients receiving immunosuppressants, immunological assessment of whether a live attenuated vaccine can be administered safely is important. For patients who can be vaccinated, administration of the vaccine during a period when the underlying disease is stable is preferable.
Relationship between degree of immunodeficiency, risk of infection and safety of live vaccines
Data availability
The data of this study are available from the corresponding author, Koichi Kamei, upon reasonable request.
References
Rubin LG, Levin MJ, Ljungman P, Davies EG, Avery R, Tomblyn M, Bousvaros A, Dhanireddy S, Sung L, Keyserling H, Kang I, Infectious Diseases Society of America (2014) 2013 IDSA clinical practice guideline for vaccination of the immunocompromised host. Clin Infect Dis 58:e44–e100. https://doi.org/10.1093/cid/cit684
Lynfield R, Herrin JT, Rubin RH (1992) Varicella in pediatric renal transplant recipients. Pediatrics 90:216–220
Broyer M, Tete MJ, Guest G, Gagnadoux MF, Rouzioux C (1997) Varicella and zoster in children after kidney transplantation: long-term results of vaccination. Pediatrics 99:35–39. https://doi.org/10.1542/peds.99.1.35
Feldhoff CM, Balfour HH Jr, Simmons RL, Najarian JS, Mauer SM (1981) Varicella in children with renal transplants. J Pediatr 98:25–31. https://doi.org/10.1016/s0022-3476(81)80527-6
Kashtan CE, Cook M, Chavers BM, Mauer SM, Nevins TE (1997) Outcome of varicella in 66 pediatric renal transplant recipients. J Pediatr 131:874–877. https://doi.org/10.1016/s0022-3476(97)70036-2
Furth SL, Sullivan EK, Neu AM, Tejani A, Fivush BA (1997) Varicella in the first year after renal transplantation: a report of the North American Pediatric Renal Transplant Cooperative Study (NAPRTCS). Pediatr Transplant 1:37–42
McGregor RS, Zitelli BJ, Urbach AH, Malatack JJ, Gartner JC Jr (1989) Varicella in pediatric orthotopic liver transplant recipients. Pediatrics 83:256–261
Pacini-Edelstein SJ, Mehra M, Ament ME, Vargas JH, Martin MG, McDiarmid SV (2003) Varicella in pediatric liver transplant patients: a retrospective analysis of treatment and outcome. J Pediatr Gastroenterol Nutr 37:183–186. https://doi.org/10.1097/00005176-200308000-00018
Dodd DA, Burger J, Edwards KM, Dummer JS (2001) Varicella in a pediatric heart transplant population on nonsteroid maintenance immunosuppression. Pediatrics 108:E80. https://doi.org/10.1542/peds.108.5.e80
Morgan ER, Smalley LA (1983) Varicella in immunocompromised children. Incidence of abdominal pain and organ involvement. Am J Dis Child 137:883–885. https://doi.org/10.1001/archpedi.1983.02140350057014
Feldman S, Hughes WT, Daniel CB (1975) Varicella in children with cancer: Seventy-seven cases. Pediatrics 56:388–397
Bradley JR, Wreghitt TG, Evans DB (1987) Varicella in adult renal transplant recipients. Nephrol Dial Transplant 1:242–245
Errasti P, Alvarez ML, Gomez G, Lavilla FJ, Garcia N, Ballester B, García I, Purroy A (1999) Varicella in four adult renal transplant recipients. Transplant Proc 31:2341–2342. https://doi.org/10.1016/s0041-1345(99)00369-3
Heininger U, Seward JF (2006) Varicella. Lancet 368:1365–1376. https://doi.org/10.1016/S0140-6736(06)69561-5
Kaplan LJ, Daum RS, Smaron M, McCarthy CA (1992) Severe measles in immunocompromised patients. JAMA 267:1237–1241
Hughes I, Jenney ME, Newton RW, Morris DJ, Klapper PE (1993) Measles encephalitis during immunosuppressive treatment for acute lymphoblastic leukaemia. Arch Dis Child 68:775–778. https://doi.org/10.1136/adc.68.6.775
Kernahan J, McQuillin J, Craft AW (1987) Measles in children who have malignant disease. Br Med J (Clin Res Ed) 295:15–18. https://doi.org/10.1136/bmj.295.6589.15
Gray MM, Hann IM, Glass S, Eden OB, Jones PM, Stevens RF (1987) Mortality and morbidity caused by measles in children with malignant disease attending four major treatment centres: a retrospective review. Br Med J (Clin Res Ed) 295:19–22. https://doi.org/10.1136/bmj.295.6589.19
Nakano T, Shimono Y, Sugiyama K, Nishihara H, Higashigawa M, Komada Y, Ito M, Sakurai M, Yoshida A, Kitamura K, Ihara T, Kamiya H, Hamazaki M, Sata T (1996) Clinical features of measles in immunocompromised children. Acta Paediatr Jpn 38:212–217. https://doi.org/10.1111/j.1442-200x.1996.tb03472.x
Bakshi N, Lawson J, Hanson R, Ames C, Vinters HV (1996) Fatal mumps meningoencephalitis in a child with severe combined immunodeficiency after bone marrow transplantation. J Child Neurol 11:159–162. https://doi.org/10.1177/088307389601100218
Rand EB, McCarthy CA, Whitington PF (1993) Measles vaccination after orthotopic liver transplantation. J Pediatr 123:87–89. https://doi.org/10.1016/s0022-3476(05)81545-8
Zamora I, Simon JM, Da Silva ME, Piqueras AI (1994) Attenuated varicella virus vaccine in children with renal transplants. Pediatr Nephrol 8:190–192. https://doi.org/10.1007/BF00865476
Kano H, Mizuta K, Sakakihara Y, Kato H, Miki Y, Shibuya N, Saito M, Narita M, Kawarasaki H, Igarashi T, Hashizume K, Iwata T (2002) Efficacy and safety of immunization for pre- and post- liver transplant children. Transplantation 74:543–550. https://doi.org/10.1097/00007890-200208270-00020
Levitsky J, Te HS, Faust TW, Cohen SM (2002) Varicella infection following varicella vaccination in a liver transplant recipient. Am J Transplant 2:880–882. https://doi.org/10.1034/j.1600-6143.2002.20912.x
Chaves TdoS, Lopes MH, de Souza VA, de Souza Dos Santos S, Pereira LM, Reis AD, David-Neto E (2005) Seroprevalence of antibodies against varicella-zoster virus and response to the varicella vaccine in pediatric renal transplant patients. Pediatr Transplant 9:192–196. https://doi.org/10.1111/j.1399-3046.2005.00279.x
Weinberg A, Horslen SP, Kaufman SS, Jesser R, Devoll-Zabrocki A, Fleckten BL, Kochanowicz S, Seipel KR, Levin MJ (2006) Safety and immunogenicity of varicella-zoster virus vaccine in pediatric liver and intestine transplant recipients. Am J Transplant 6:565–658. https://doi.org/10.1111/j.1600-6143.2005.01210.x
Khan S, Erlichman J, Rand EB (2006) Live virus immunization after orthotopic liver transplantation. Pediatr Transplant 10:78–82. https://doi.org/10.1111/j.1399-3046.2005.00403.x
Kraft JN, Shaw JC (2006) Varicella infection caused by Oka strain vaccine in a heart transplant recipient. Arch Dermatol 142:943–945. https://doi.org/10.1001/archderm.142.7.943
Lu Y, Bousvaros A (2010) Varicella vaccination in children with inflammatory bowel disease receiving immunosuppressive therapy. J Pediatr Gastroenterol Nutr 50:562–565. https://doi.org/10.1097/MPG.0b013e3181bab351
Posfay-Barbe KM, Pittet LF, Sottas C, Grillet S, Wildhaber BE, Rodriguez M, Kaiser L, Belli DC, McLin VA, Siegrist CA (2012) Varicella-zoster immunization in pediatric liver transplant recipients: safe and immunogenic. Am J Transplant 12:2974–2985. https://doi.org/10.1111/j.1600-6143.2012.04273.x
Azevedo LS, Lasmar EP, Contieri FL, Boin I, Percegona L, Saber LT, Selistre LS, Netto MV, Moreira MC, Carvalho RM, Bruno RM, Ferreira TC, David-Neto E (2012) Yellow fever vaccination in organ transplanted patients: is it safe? A multicenter study. Transpl Infect Dis 14:237–241. https://doi.org/10.1111/j.1399-3062.2011.00686.x
Slifka MK, Hammarlund E, Lewis MW, Poore EA, Hanifin JM, Marr KA, Hecox D, Amanna IJ (2013) Antiviral immune response after live yellow fever vaccination of a kidney transplant recipient treated with IVIG. Transplantation 95:e59–e61. https://doi.org/10.1097/TP.0b013e31828c6d9e
Kawano Y, Suzuki M, Kawada J, Kimura H, Kamei H, Ohnishi Y, Ono Y, Uchida H, Ogura Y, Ito Y (2015) Effectiveness and safety of immunization with live-attenuated and inactivated vaccines for pediatric liver transplantation recipients. Vaccine 33:1440–1445. https://doi.org/10.1016/j.vaccine.2015.01.075
Shinjoh M, Miyairi I, Hoshino K, Takahashi T, Nakayama T (2008) Effective and safe immunizations with live-attenuated vaccines for children after living donor liver transplantation. Vaccine 26:6859–6863
Shinjoh M, Hoshino K, Takahashi T, Nakayama T (2015) Updated data on effective and safe immunizations with live-attenuated vaccines for children after living donor liver transplantation. Vaccine 33:701–707. https://doi.org/10.1016/j.vaccine.2008.09.076
Kamei K, Miyairi I, Ishikura K, Ogura M, Shoji K, Funaki T, Ito R, Arai K, Abe J, Kawai T, Onodera M, Ito S (2018) Prospective Study of Live Attenuated Vaccines for Patients with Nephrotic Syndrome Receiving Immunosuppressive Agents. J Pediatr 196:217–222. https://doi.org/10.1016/j.jpeds
Verolet CM, Pittet LF, Wildhaber BE, McLin VA, Rodriguez M, Grillet S, Siegrist CA, Posfay-Barbe KM (2019) Long-term seroprotection of varicella-zoster immunization in pediatric liver transplant recipients. Transplantation 103:e355–e364. https://doi.org/10.1097/TP.0000000000002866
Pittet LF, Verolet CM, McLin VA, Wildhaber BE, Rodriguez M, Cherpillod P, Kaiser L, Siegrist CA, Posfay-Barbe KM (2019) Multimodal safety assessment of measles-mumps-rubella vaccination after pediatric liver transplantation. Am J Transplant 19:844–854. https://doi.org/10.1111/ajt.15101
Ortiz-Brizuela E, Leal-Vega F, Cuellar-Rodríguez J, Bobadilla-Del-Valle M, Ponce-de-León A (2019) Vaccine-derived varicella zoster infection in a kidney transplant recipient after zoster vaccine live administration. Vaccine 37:3576–3579. https://doi.org/10.1016/j.vaccine.2019.05.017
de Sousa MV, Zollner RL, Stucchi RSB, Boin IFSF, de Ataide EC, Mazzali M (2019) Yellow fever disease in a renal transplant recipient: Case report and literature review. Transpl Infect Dis 21:e13151. https://doi.org/10.1111/tid.13151
Bobrowski AE, Muller WJ (2020) Varicella infection following vaccination in a pediatric kidney transplant recipient. Pediatr Transplant 24:e13667. https://doi.org/10.1111/petr.13667
Kamei K, Miyairi I, Ishikura K, Ogura M, Shoji K, Arai K, Ito R, Kawai T, Ito S (2020) Prospective study of live attenuated vaccines for patients receiving immunosuppressive agents. PLoS One 15:e0240217. https://doi.org/10.1371/journal.pone.0240217
Funaki T, Shoji K, Fukuda A, Sakamoto S, Kasahara M, Miyairi I (2021) Safety of LAVs administered after pediatric LT. Pediatr Transplant 25:e13937. https://doi.org/10.1111/petr.13937
Kamei K, Miyairi I, Shoji K, Arai K, Kawai T, Ogura M, Ishikura K, Sako M, Nakamura H (2021) Live attenuated vaccines under immunosuppressive agents or biological agents: survey and clinical data from Japan. Eur J Pediatr 180:1847–1854. https://doi.org/10.1007/s00431-021-03927-1
Newman AM, Posch LC, Gianchetti L, Rand EB, Mohammad S, Downes KJ, Muller WJ (2022) Live virus vaccination following pediatric liver transplantation: Outcomes from two academic children’s hospitals. Am J Transplant 22:1201–1212. https://doi.org/10.1111/ajt.16937
Yri OE, Torfoss D, Hungnes O, Tierens A, Waalen K, Nordøy T, Dudman S, Kilander A, Wader KF, Ostenstad B, Ekanger R, Meyer P, Kolstad A (2011) Rituximab blocks protective serologic response to influenza A (H1N1) 2009 vaccination in lymphoma patients during or within 6 months after treatment. Blood 118:6769–6771. https://doi.org/10.1182/blood-2011-08-372649
Avouac J, Miceli-Richard C, Combier A, Steelandt A, Fogel O, Mariaggi AA, Meritet JF, Rozenberg F, Molto A, Allanore Y (2022) Risk factors of impaired humoral response to COVID-19 vaccination in rituximab-treated patients. Rheumatology (Oxford) 61(SI2):SI163–SI168. https://doi.org/10.1093/rheumatology/keab815
Stefanski AL, Rincon-Arevalo H, Schrezenmeier E, Karberg K, Szelinski F, Ritter J, Jahrsdörfer B, Schrezenmeier H, Ludwig C, Sattler A, Kotsch K, Chen Y, Claußnitzer A, Haibel H, Proft F, Guerra G, Durek P, Heinrich F, Ferreira-Gomes M, Burmester GR, Radbruch A, Mashreghi MF, Lino AC, Dörner T (2022) B Cell Numbers Predict Humoral and Cellular Response Upon SARS-CoV-2 Vaccination Among Patients Treated With Rituximab. Arthritis Rheumatol 74:934–947. https://doi.org/10.1002/art.42060
Acknowledgements
We would like to thank Forte Science Communications for editing a draft of this manuscript.
Funding
There was no external funding for this manuscript.
Author information
Authors and Affiliations
Corresponding author
Ethics declarations
Competing interests
Koichi Kamei has obtained research funding from the Public Foundation of Vaccination Research Center, the Terumo Foundation for Life Sciences and Arts, and the Taiju Life Social Welfare Foundation; donations from Chugai Pharmaceutical Co. Ltd., Astellas Pharma Inc., Ono Pharmaceutical Co. Ltd., Teijin Pharma Ltd., Shionogi Co. Ltd., and Otsuka Pharmaceutical Co. Ltd.; and lecture fees from Tanabe Mitsubishi Pharma, Baxter Ltd., and Zenyaku Kogyo Co. Ltd.
Additional information
Publisher's note
Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
Rights and permissions
Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.
About this article
Cite this article
Kamei, K. Live attenuated vaccines in patients receiving immunosuppressive agents. Pediatr Nephrol 38, 3889–3900 (2023). https://doi.org/10.1007/s00467-023-05969-z
Received:
Revised:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s00467-023-05969-z