Perceptions of yellow fever emergency mass vaccinations among vulnerable groups in Uganda: A qualitative study.

BACKGROUND: Yellow fever (YF), a mosquito-borne viral hemorrhagic fever, is endemic in Uganda and causes frequent outbreaks. A total of 1.6 million people were vaccinated during emergency mass immunization campaigns in 2011 and 2016. This study explored local perceptions of YF emergency mass immunization among vulnerable groups to inform future vaccination campaigns. METHODOLOGY: In this qualitative study, we conducted 43 semi-structured interviews, 4 focus group discussions, and 10 expert interviews with 76 participants. Data were collected in six affected districts with emergency mass vaccination. We included vulnerable groups (people ≥ 65 years and pregnant women) who are typically excluded from YF vaccination except during mass immunization. Data analysis was conducted using grounded theory. Inductive coding was utilized, progressing through open, axial, and selective coding. PRINCIPAL FINDINGS: Participants relied on community sources for information about the YF mass vaccination. Information was disseminated door-to-door, in community spaces, during religious gatherings, and on the radio. However, most respondents had no knowledge of the vaccine, and it was unclear to them whether a booster dose was required. In addition, the simultaneous presidential election during the mass vaccination campaign led to suspicion and resistance to vaccination. The lack of reliable and trustworthy information and the politicization of vaccination campaigns reinforced mistrust of YF vaccines. CONCLUSIONS/SIGNIFICANCE: People in remote areas affected by YF outbreaks rely on community sources of information. We therefore recommend improving health education, communication, and engagement through respected and trusted community members. Vaccination campaigns can never be seen as detached from political systems and power relations.

Advancing molecular modeling and reverse vaccinology in broad-spectrum yellow fever virus vaccine development.

Yellow fever outbreaks are prevalent, particularly in endemic regions. Given the lack of an established treatment for this disease, significant attention has been directed toward managing this arbovirus. In response, we developed a multiepitope vaccine designed to elicit an immune response, utilizing advanced immunoinformatic and molecular modeling techniques. To achieve this, we predicted B- and T-cell epitopes using the sequences from all structural (E, prM, and C) and nonstructural proteins of 196 YFV strains. Through comprehensive analysis, we identified 10 cytotoxic T-lymphocyte (CTL) and 5T-helper (Th) epitopes that exhibited overlap with B-lymphocyte epitopes. These epitopes were further evaluated for their affinity to a wide range of human leukocyte antigen system alleles and were rigorously tested for antigenicity, immunogenicity, allergenicity, toxicity, and conservation. These epitopes were linked to an adjuvant ( ß -defensin) and to each other using ligands, resulting in a vaccine sequence with appropriate physicochemical properties. The 3D structure of this sequence was created, improved, and quality checked; then it was anchored to the Toll-like receptor. Molecular Dynamics and Quantum Mechanics/Molecular Mechanics simulations were employed to enhance the accuracy of docking calculations, with the QM portion of the simulations carried out utilizing the density functional theory formalism. Moreover, the inoculation model was able to provide an optimal codon sequence that was inserted into the pET-28a( +) vector for in silico cloning and could even stimulate highly relevant humoral and cellular immunological responses. Overall, these results suggest that the designed multi-epitope vaccine can serve as prophylaxis against the yellow fever virus.

YF17D-based vaccines - standing on the shoulders of a giant.

Live-attenuated yellow fever vaccine (YF17D) was developed in the 1930s as the first ever empirically derived human vaccine. Ninety years later, it is still a benchmark for vaccines made today. YF17D triggers a particularly broad and polyfunctional response engaging multiple arms of innate, humoral and cellular immunity. This unique immunogenicity translates into an extraordinary vaccine efficacy and outstanding longevity of protection, possibly by single-dose immunization. More recently, progress in molecular virology and synthetic biology allowed engineering of YF17D as a powerful vector and promising platform for the development of novel recombinant live vaccines, including two licensed vaccines against Japanese encephalitis and dengue, even in paediatric use. Likewise, numerous chimeric and transgenic preclinical candidates have been described. These include prophylactic vaccines against emerging viral infections (e.g. Lassa, Zika and SARS-CoV-2) and parasitic diseases (e.g. malaria), as well as therapeutic applications targeting persistent infections (e.g. HIV and chronic hepatitis), and cancer. Efforts to overcome historical safety concerns and manufacturing challenges are ongoing and pave the way for wider use of YF17D-based vaccines. In this review, we summarize recent insights regarding YF17D as vaccine platform, and how YF17D-based vaccines may complement as well as differentiate from other emerging modalities in response to unmet medical needs and for pandemic preparedness.

Cynomolgus macaques as a translational model of human immune responses to yellow fever 17D vaccination.

The non-human primate (NHP) model (specifically rhesus and cynomolgus macaques) has facilitated our understanding of the pathogenic mechanisms of yellow fever (YF) disease and allowed the evaluation of the safety and efficacy of YF-17D vaccines. However, the accuracy of this model in mimicking vaccine-induced immunity in humans remains to be fully determined. We used a systems biology approach to compare hematological, biochemical, transcriptomic, and innate and antibody-mediated immune responses in cynomolgus macaques and human participants following YF-17D vaccination. Immune response progression in cynomolgus macaques followed a similar course as in adult humans but with a slightly earlier onset. Yellow fever virus neutralizing antibody responses occurred earlier in cynomolgus macaques [by Day 7[(D7)], but titers > 10 were reached in both species by D14 post-vaccination and were not significantly different by D28 [plaque reduction neutralization assay (PRNT)50 titers 3.6 Log vs 3.5 Log in cynomolgus macaques and human participants, respectively; P = 0.821]. Changes in neutrophils, NK cells, monocytes, and T- and B-cell frequencies were higher in cynomolgus macaques and persisted for 4 weeks versus less than 2 weeks in humans. Low levels of systemic inflammatory cytokines (IL-1RA, IL-8, MIP-1α, IP-10, MCP-1, or VEGF) were detected in either or both species but with no or only slight changes versus baseline. Similar changes in gene expression profiles were elicited in both species. These included enriched and up-regulated type I IFN-associated viral sensing, antiviral innate response, and dendritic cell activation pathways D3-D7 post-vaccination in both species. Hematological and blood biochemical parameters remained relatively unchanged versus baseline in both species. Low-level YF-17D viremia (RNAemia) was transiently detected in some cynomolgus macaques [28% (5/18)] but generally absent in humans [except one participant (5%; 1/20)].IMPORTANCECynomolgus macaques were confirmed as a valid surrogate model for replicating YF-17D vaccine-induced responses in humans and suggest a key role for type I IFN.

Yellow fever neutralizing antibody seroprevalence proportion and titers in previously vaccinated adults with chronic kidney disease.

Studies on yellow fever vaccine (YF) in chronic kidney disease (CKD) patients are scarce. This cross-sectional study aimed to evaluate YF neutralizing antibody seroprevalence and titers in previously vaccinated adults with CKD, on dialysis (D-CKD) or not (ND-CKD), compared to healthy persons. The micro Plaque Reduction Neutralization-Horseradish Peroxidase (µPRN-HP) test was used. Antibody titers were expressed as the reciprocal of the highest dilution that neutralized the challenge virus by 50 % (µPRN50). Seropositivity cut-off was set at ≥ 1:100. We included 153 participants: 46 ND-CKD, 50 D-CKD and 57 healthy adults. Median ages were 58.3, 55 and 52.2 years, respectively. Median time since YF vaccination was 22.3, 18.5 and 48.3 months respectively. There were no statistically significant differences in YF seroprevalence and neutralizing antibodies titers among groups: 100 % of ND-CKD; 96 % of D-CKD and 100 % of healthy participants were seropositive. Geometric mean titers (GMT) were 818.5, 683.0 and 665.5, respectively (p = 0.289).

Humoral immunogenicity of primary yellow fever vaccination in infants and children: a systematic review, meta-analysis and meta-regression.

BACKGROUND: Vaccination plays a critical role in mitigating the burden associated with yellow fever (YF). However, there is a lack of comprehensive evidence on the humoral response to primary vaccination in the paediatric population, with several questions debated, including the response when the vaccine is administered at early ages, the effect of co-administration with other vaccines, the duration of immunity and the use of fractional doses, among others. This study summarizes the existing evidence regarding the humoral response to primary YF vaccination in infants and children. METHODS: Studies on the humoral response to primary YF vaccination in children aged 12 years or younger were reviewed. The humoral vaccine response rate (VRR), i.e. the proportion of children who tested positive for vaccine-induced YF-specific neutralizing antibodies, was pooled through random-effects meta-analysis and categorized based on the time elapsed since vaccination. Subgroup, meta-regression and sensitivity analyses were performed. RESULTS: A total of 33 articles met the inclusion criteria, with all but one conducted in countries where YF is endemic. A total of 14 028 infants and children entered this systematic review. Within three months following vaccination, the pooled VRR was 91.9% (95% CI 89.8-93.9). A lower VRR was observed with the 17DD vaccine at the meta-regression analysis. No significant differences in immunogenicity outcomes were observed based on age, administration route, co-administration with other vaccines, or fractional dosing. Results also indicate a decline in VRR over time. CONCLUSIONS: Primary YF vaccination effectively provides humoral immunity in paediatric population. However, humoral response declines over time, and this decline is observable after the first 18 months following vaccination. A differential response according to the vaccine substrain was also observed. This research has valuable implications for stimulating further research on the primary YF vaccination in infants and children, as well as for informing future policies.

Immunological response to fractional-dose yellow fever vaccine administered during an outbreak in Kinshasa, Democratic Republic of the Congo: results 5 years after vaccination from a prospective cohort study.

BACKGROUND: In 2016, outbreaks of yellow fever in Angola and the Democratic Republic of the Congo led to a global vaccine shortage. A fractional dose of 17DD yellow fever vaccine (containing one-fifth [0·1 ml] of the standard dose) was used during a pre-emptive mass campaign in August, 2016, in Kinshasa, Democratic Republic of the Congo among children aged 2 years and older and non-pregnant adults (ie, those aged 18 years and older). 1 year following vaccination, 97% of participants were seropositive; however, the long-term durability of the immune response is unknown. We aimed to conduct a prospective cohort study and invited participants enrolled in the previous evaluation to return 5 years after vaccination to assess durability of the immune response. METHODS: Participants returned to one of six health facilities in Kinshasa in 2021, where study staff collected a brief medical history and blood specimen. We assessed neutralising antibody titres against yellow fever virus using a plaque reduction neutralisation test with a 50% cutoff (PRNT50). Participants with a PRNT50 titre of 10 or higher were considered seropositive. The primary outcome was the proportion of participants seropositive at 5 years. FINDINGS: Among the 764 participants enrolled, 566 (74%) completed the 5-year visit. 5 years after vaccination, 539 (95·2%, 95% CI 93·2-96·7) participants were seropositive, including 361 (94·3%, 91·5-96·2) of 383 who were seronegative and 178 (97·3%, 93·8-98·8) of 183 who were seropositive at baseline. Geometric mean titres (GMTs) differed significantly across age groups for those who were initially seronegative with the lowest GMT among those aged 2-5 years and highest among those aged 13 years and older. INTERPRETATION: A fractional dose of the 17DD yellow fever vaccine induced an immunologic response with detectable titres at 5 years among the majority of participants in the Democratic Republic of the Congo. These findings support the use of fractional-dose vaccination for outbreak prevention with the potential for sustained immunity. FUNDING: Gavi, the Vaccine Alliance through the CDC Foundation. TRANSLATION: For the French translation of the abstract see Supplementary Materials section.

Safety of the yellow fever vaccine in people living with HIV: a longitudinal study exploring post-vaccination viremia and hematological and liver kinetics.

BACKGROUND: Safety data on the yellow fever vaccine 17DD in People Living with HIV (PLWH) are limited. This study explored the occurrence of post-vaccination 17DD viremia and the kinetics of hematological and liver laboratorial parameters in PLWH and HIV-uninfected participants [HIV(-) controls]. METHODS: We conducted a secondary analysis of a longitudinal interventional trial (NCT03132311) study that enrolled PLWH and HIV(-) controls to receive a single 17DD dose and were followed at 5, 30 and 365 days after vaccination in Rio de Janeiro, Brazil. 17DD viremia (obtained throughreal-time PCR and plaque forming units' assays), hematological (neutrophils, lymphocytes and platelets counts) and liver enzymes (ALT and AST) results were assessed at baseline and Days 5 and 30 post-vaccination. Logistic regression models explored factors associated with the odds of having positive 17DD viremia. Linear regression models explored variables associated with hematological and liver enzymes results at Day 5. RESULTS: A total of 202 PLWH with CD4 ≥ 200 cells/µL and 68 HIV(-) controls were included in the analyses. 17DD viremia was found in 20.0 % of the participants and was twice more frequent in PLWH than in HIV(-) controls (22.8% vs. 11.8 %, p-value < 0.001). Neutrophils, lymphocytes and platelets counts dropped at Day 5 and returned to baseline values at Day 30. 17DD viremia was associated with lower nadir of lymphocytes and platelets at Day 5. ALT levels did not increase post-vaccination and were not associated with 17DD viremia. CONCLUSIONS: 17DD was safe and well-tolerated in PLWH with CD4 ≥ 200 cells/µL. Post-vaccination viremia was more frequent in PLWH than in controls. Transient and self-limited decreases in lymphocytes and neutrophils occurred early after vaccination. 17DD viremia was associated with lower lymphocytes and platelets nadir after vaccination. We did not observe elevations in ALT after 17DD vaccination.

Long-term immunity following yellow fever vaccination: a systematic review and meta-analysis.

BACKGROUND: Long-term immunity following yellow fever vaccination remains controversial. We aimed to summarise the literature regarding the long-term protection (≥10 years) conveyed by a single dose of yellow fever vaccination. METHODS: In this systematic review and meta-analysis, we searched 11 databases from database inception to Aug 24, 2023. We included cohort and cross-sectional studies reporting immunogenicity outcomes for children or adults who received a single dose of yellow fever vaccination 10 or more years ago. Case series and single case reports were excluded. Participants who received more than one dose of yellow fever vaccination before measurement of the outcome were excluded. Identified records were reviewed by two independent reviewers. The primary outcome of the meta-analysis was the pooled seroprotection rate. Risk of bias was assessed with the Risk Of Bias In Non-randomized Studies of Interventions tool, and the Joanna Briggs Institute tool for analytical cross-sectional studies. Studies of moderate or good quality that reported seroprotection were included for random-effects meta-analysis and stratified by endemicity and specific risk groups. The study was registered with PROSPERO, CRD42023384087. FINDINGS: Of the 7363 articles identified by our search, 39 were eligible for inclusion for systematic review. These studies comprised 2895 individuals vaccinated 10-60 years ago. 20 studies were included in the meta-analysis. Pooled seroprotection rates were 94% (95% CI 86-99) among healthy adults in a non-endemic setting (mostly travellers) and 76% (65-85) in an endemic setting (all Brazilian studies). The pooled seroprotection rate was 47% (35-60) in children (aged 9-23 months at time of vaccination) and 61% (38-82) in people living with HIV. Reported criteria for seroprotection were highly heterogeneous. INTERPRETATION: The gathered evidence suggests that a single dose of yellow fever vaccination provides lifelong protection in travellers. However, in people living with HIV and children (younger than 2 years), booster doses might still be required because lower proportions of vaccinees were seroprotected 10 or more years post-vaccination. Lower observed seroprotection rates among residents of endemic areas were partly explained by the use of a higher cutoff for seroprotection that was applied in Brazil. Studies from sub-Saharan Africa were scarce and of low quality; thus no conclusions could be drawn for this region. FUNDING: None.

Phylogenetic analysis reveals a new introduction of Yellow Fever virus in São Paulo State, Brazil, 2023.

Yellow Fever (YF) is a viral arbovirosis of Public Health importance. In Brazil, surveillance is focused mainly on detecting epizootic events of Platyrrhini. Herein, we compared the detection and phylogenetic analysis of YF virus in two neotropical primates (NTP), a Callithrix detected in the previous epidemic period (2016-2020), and a Callicebus nigrifons, showing a new introduction of YF in 2023. This paper illustrates the importance of joint actions of laboratory and field teams to ensure quick response to Public Health emergencies, such as the intensification of vaccination of susceptible human populations.

Incidence of anaphylaxis to YF-VAX® yellow fever vaccination: a retrospective evaluation of vaccine adverse event reports 1999-2018.

BACKGROUND: The incidence of anaphylaxis after receipt of yellow fever (YF) vaccine is highly variable based upon previously published reports. Anaphylaxis after receiving the YF vaccine has been reported to range from 0 up to 22 per 1 000 000 doses. Our clinical experience suggested increased incidence, which prompted our investigation. We sought to evaluate the current incidence rate of anaphylaxis after receipt of the 17D-204 strain YF-VAX® brand reported in the US. METHODS: We performed a retrospective review of the Vaccine Adverse Event Reporting System (VAERS) reports of anaphylaxis after receiving the YF-VAX vaccine occurring between 1 October 1999 and 30 September 2018. We utilized the Brighton Collaboration Case Definition and inclusion determination was made by a board-certified allergist. We also obtained the total number of YF-VAX doses distributed across the US during this same time-period and then calculated an updated incidence rate of YF-VAX vaccine-associated anaphylaxis. RESULTS: We identified 132 potential cases of possible or probable anaphylaxis. Of these, 111 met inclusion criteria: level 1 (n = 51), level 2 (n = 59) and level 3 (n = 1). The manufacturer reported a total distribution of 7 624 160 doses of YF-VAX from 1 October 1999 to 30 September 2018. The calculated incidence rate of YF-VAX vaccine-associated anaphylaxis is estimated at 14.6 events per 1 000 000 doses. CONCLUSIONS: We conclude the estimated rate of anaphylaxis per VAERS reports is 14.6 events per 1 000 000 doses after YF-VAX vaccination. This is consistent with some previous reports and substantially higher than rates of anaphylaxis after other vaccines.

Yellow fever vaccine-associated neurologic and viscerotropic disease: a 10-year case series of the French National Reference Center for Arboviruses with clinical and immunological insights.

BACKGROUND: Immunization against the Yellow fever virus (YFV) with the 17D live-attenuated vaccine is the most effective way to prevent the disease. However, unexpected severe adverse events can occur. They consist in a neurological impairment - neurological disease (YEL-AND), a YF-like illness - viscerotropic disease (YEL-AVD) or anaphylaxis. In this article, we describe the epidemiology, clinical and biological features of YEL-AND and YEL-AVD cases reported to the French National Reference Center for Arboviruses (NRCA) in the past 10 years. METHODS: We conducted a national, retrospective study using the database of the NRCA from June 2012 to June 2022. All patients whose biological samples were sent to the NRCA for detection of YFV by serology and/or RT-qPCR for a suspected vaccine-associated adverse event were included. We collected data by reading medical records and conducted complementary neuro-immunological analysis, followed by a search for autoimmunity against type-1-interferon when samples were available at the NRCA. RESULTS: There were 10 cases of YEL-AND and 2 cases of YEL-AVD reported to the NRCA in the past 10 years, which represented an overall incidence of 0.6 for 100 000 doses. A total of 6/12 cases were previously healthy patients (50%, mean age 31 years), and 4/12 cases had cardiovascular co-morbidities (42%, mean age 56 years). The majority of YEL-AND had a favourable outcome at 6 months of follow up. One YEL-AVD patient passed. In secondary analyses, we evidenced a significant blood cerebrospinal fluid (CSF) barrier dysfunction, without intrathecal synthesis of immunoglobulin and without argument for a neuron damage. We further detected a significant rate of anti-type-1alpha interferon antibodies in 3/10 tested patients (2 YEL-AND and 1 YEL-AVD). CONCLUSION: YEL-AND and YEL-AVD are rare events that can underlie defect in the innate immunity of apparently healthy or mild co-morbid subjects. Outcome was generally favourable in the YEL-AND cases of our series, but still life-threatening or even fatal in the YEL-AVD cases.

Differential gene expression of cytokines, receptors, and miRNAs in individuals living with HIV-1 and vaccinated against yellow fever.

Between 2016 and 2018, Brazil faced a yellow fever (YF) outbreak, which led to an expansion of vaccination coverage. The coexistence of the YF outbreak and the HIV-1 epidemic in Brazil raised concerns regarding the immune response and vaccine effectiveness in individuals living with HIV (PLWH). The aim of this study was to investigate the immune response to YF vaccination in PLWH and HIV-uninfected individuals as controls. Transcript levels of immunomodulatory molecules, including IL-6, IL-10, IL-21, TGF-ß, CD19, CD163, miR-21, miR-146, and miR-155, were measured using RTqPCR. TCD4+ cells were evaluated by cytometry, and neutralizing antibody (Nab) titers were detected by a micro plaque-reduction neutralization test. The findings of our study revealed several noteworthy observations. First, there was a notable reduction in the circulation of TCD4+ cells postvaccination. Among people living with HIV (PLWH), we observed an increase in the expression of IL-10 following vaccination, while IL-6 expression was diminished in PLWH with lower TCD4+ counts. Furthermore, we identified the downregulation of CD19 and TGF-ß, along with the upregulation of IL-21 and CD163. Notably, we observed positive correlations between the levels of IL-10/IL-21, IL-10/CD163, and IL-6/CD19. Additionally, there was a positive correlation between miRNAs 146 and 155. It is important to emphasize that all participants exhibited robust neutralizing antibody responses after receiving 17DD YF vaccination. In this context, the gene expression data presented can be useful for biomarker studies of protective antibodies induced by YF vaccination. This study sheds light on immune mechanisms in individuals living with HIV and YF vaccination.

High coverage and timeliness of vaccination of children under 6 years of age in Risaralda, Colombia.

This study determined the coverage and timeliness of immunization in children <6 y from Risaralda, Colombia. A retrospective cross-sectional study evaluated data from a vaccination coverage and timeliness verification survey conducted in 2019, including 2457 children <6 y from Risaralda, Colombia. Variables included demographics, a record of vaccinations included in the Colombian Vaccination Plan, and date of immunization. Vaccination was defined as timely until 29 d after the day established by the plan. Coverage was over 95% for all vaccinations, except the boosters of diphtheria/pertussis/tetanus (DTP) and oral polio at 18 months (91.0%), influenza (85.6%), and yellow fever (49.2%). Most surveyed children demonstrated very high timeliness of vaccination, with values close to, or over, 90%, although there were exceptions for pentavalent (DTP+Haemophilus influenzae type B+hepatitis B) and polio vaccines at 6 months (79.4%), influenza (85.6%), and yellow fever (49.2%). Before the COVID-19 pandemic, Colombian Vaccination Plan demonstrated high coverage and timeliness of vaccination of children <6 y of age; however, timeliness for the third dose of DTP-Hib-HBV and polio showed opportunities for improvement.

Immunogenicity and reactogenicity of yellow fever vaccine in people with HIV.

OBJECTIVE: To evaluate immunogenicity and reactogenicity of yellow fever (YF) vaccine in people with HIV (PWH) compared to HIV-uninfected controls. DESIGN: In this longitudinal interventional trial (NCT03132311), PWH with CD4 + cell count ≥200 cells/µl and controls, aged 18-59, without a previous history of YF vaccination received a single standard dose of YF vaccine (17DD) and were followed at Days 5, 30 and Year 1. METHODS: YF-neutralization titers were measured at Days 0, 30 and Year 1 and geometric mean titers (GMT) were calculated. Adverse events (AE) and YF virus detection were measured at Days 5 and 30. Linear regression evaluated factors associated with YF-neutralization titers. RESULTS: Two hundred and eighteen PWH and 82 controls were included. At baseline, all PWH were using antiretroviral therapy; 92.6% had undetectable HIV viral load (VL) and median CD4 + cell count was 630 cells/µl [interquartile range (IQR) 463-888]. YF vaccine was safe and there were no serious AEs. At Day 30, seroconversion was observed in 98.6% of PWH [95% confidence interval (CI): 95.6-99.6] and in 100% of controls (95% CI: 93.9-100); at Year 1, 94.0% of PWH (95% CI: 89.6-96.7) and 98.4% of controls (95% CI 90.3-99.9) were seropositive. PWH had lower GMTs than controls at Day 30 and Year 1. Baseline VL >1000 copies/ml, low CD4 + cell count and low CD4 + /CD8 + ratio were associated with lower YF-neutralization titers. CONCLUSIONS: YF vaccine is safe in PWH with CD4 + cell count ≥200 cells/µl. YF vaccine immunogenicity is impaired in PWH, particularly among those with high VL, low CD4 + cell count and low CD4 + /CD8 + ratio at vaccination and YF-neutralization titers decays over time.

Compliance with yellow fever and measles vaccines in the revaccination program post-hematopoietic cell transplantation.

INTRODUCTION: Measles, mumps, rubella, and even poliomyelitis outbreaks have recently perplexed infectious disease clinicians and epidemiologists globally due to the decline in vaccination coverage rates in children and adults. Measles and yellow fever (YF) have represented an increasing burden on the Brazilian public health system in recent decades. Both diseases are preventable by live-attenuated viral vaccines (LAVV), which have restricted use in hematopoietic cell transplant (HCT) recipients. METHODS: Autologous and allogeneic HCT recipients returning for regular appointments at the outpatient clinic were invited to participate in the study. Patients transplanted for at least 2 years and with a printed copy of the vaccination record were included. RESULTS: We assessed the vaccination records of 273 HCT recipients after the second year of HCT (193 allogeneic and 80 autologous) and observed lower compliance with the YF vaccine (58 patients, 21.2%) than with the measles vaccine (138 patients, 50.5%, p ≤ .0001). This is the largest published series of YF vaccination in HCT recipients so far. No severe adverse events occurred. Although expected, chronic graft-versus-host disease (GVHD) did not affect the compliance with measles (p = .08) or YF vaccination (p = .7). Indeed, more allogeneic recipients received measles vaccine in comparison with autologous patients (p < .0001), suggesting that chronic GVHD was not the main reason for not being vaccinated. Children and allogeneic HCT were more likely to receive measles vaccine. Time elapsed from HCT >5 years favored both measles and YF vaccination. CONCLUSION: A better understanding of the reasons for low compliance with LAVV is necessary to overcome this problem.