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.

Characterization of "Off-Target" Immune Modulation Induced by Live Attenuated Yellow Fever Vaccine.

BACKGROUND: Live attenuated vaccines alter immune functions and are associated with beneficial outcomes. We previously demonstrated that live attenuated yellow fever virus (YFV) vaccine (LA-YF-Vax) dampens T-cell receptor (TCR) signaling in vitro via an RNA-based mechanism. We examined study participants before and after LA-YF-Vax to assess TCR-mediated functions in vivo. METHODS: Serum samples and peripheral blood mononuclear cells (PBMCs) were obtained before and after LA-YF-Vax (with or without additional vaccines) or quadrivalent influenza vaccine. TCR-mediated activation was determined by interleukin 2 release or phosphorylation of the lymphocyte-specific Src kinase. TCR-regulating phosphatase (protein tyrosine phosphatase receptor type E [PTPRE]) expression was also measured. RESULTS: Compared with prevaccination findings, LA-YF-Vax recipient PBMCs demonstrated transient reduction in interleukin 2 release after TCR stimulation and PTPRE levels, unlike in control participants who received quadrivalent influenza vaccine. YFV was detected in 8 of 14 participants after LA-YF-Vax. After incubation of healthy donor PBMCs in serum-derived extracellular vesicles prepared from LA-YF-Vax recipients, TCR signaling and PTPRE levels were reduced after vaccination, even in participants without detectable YFV RNA. CONCLUSIONS: LA-YF-Vax reduces TCR functions and PTPRE levels after vaccination. Extracellular vesicles from serum recapitulated this effect in healthy cells. This likely contributes to the reduced immunogenicity for heterologous vaccines after LA-YF-Vax administration. Identification of specific immune mechanisms related to vaccines should contribute to understanding of the "off-target," beneficial effects of live vaccines.

Enhanced production of yellow fever virus through tailored culture media optimization.

In the present study, an initial screening was conducted using 12 types of cell culture media, and four media with the best performance were selected for further study. The optimization of four media blend for YFV production was evaluated using an Augmented simplex centroid mixture design. Among all the different models that were investigated, the quadratic model was found to be the most appropriate model for exploring mixture design. It was found that M10 exhibited the greatest impact on YFV production, followed by M9, M4, and M1. The utilization of M1 and M4 media individually yielded higher compared to their blends with other media. The YFV titers were reduced when M1 media was combined with other media. The utilization of M9 and M10 media in combination resulted a higher viral yield compared to their respective concentrations. The optimal ratio for achieving a higher titer of YFV from primary CEFs was found to be approximately 38:62, with M9 and M10 being the most favorable media blend. The use of a media mixture led to a significant increase of virus titer up to 2.6 × 108 PFU/ml or 2 log titer yield, which is equivalent to 1.92 × 105 doses, without any changes to growth conditions or other process factors. This study concluded that the utilization of a mixture design could be efficiently employed to choose the optimal combination of media blends for enhanced viral production from cell culture.

Yellow Fever Vaccine-Associated Viscerotropic Disease among Siblings, São Paulo State, Brazil.

We describe 5 cases of yellow fever vaccine-associated viscerotropic disease (YEL-AVD) in 2 familial clusters during the 2017-2018 yellow fever (YF) vaccination campaign in São Paulo state, Brazil. The first case was that of a 40-year-old white man who died of icterohemorrhagic syndrome, which was confirmed to be YEL-AVD by using real-time reverse transcription PCR to detect 17DD YF vaccine in the liver. Ten years previously, his brother died of a clinically similar disease without a confirmed diagnosis 9 days after YF vaccination. The second cluster included 3 of 9 siblings in whom hepatitis developed in the first week after receiving fractionated doses of YF vaccine. Two of them died of hemorrhagic diathesis and renal and respiratory failure, and 17DD-YF vaccine was detected in serum samples from all patients and in the liver in 1 case. Genetic factors might play a substantial role in the incidence of YEL-AVD.

Duration of Protection After Vaccination Against Yellow Fever: A Systematic Review and Meta-Analysis.

The duration of protection after a single dose of yellow fever vaccine is a matter of debate. To summarize the current knowledge, we performed a systematic literature review and meta-analysis. Studies on the duration of protection after 1 and ≥2 vaccine doses were reviewed. Data were stratified by time since vaccination. In our meta-analysis, we used random-effects models. We identified 36 studies from 20 countries, comprising more than 17 000 participants aged 6 months to 85 years. Among healthy adults and children, pooled seroprotection rates after single vaccination dose were close to 100% by 3 months and remained high in adults for 5 to 10 years. In children vaccinated before age 2 years, the seroprotection rate was 52% within 5 years after primary vaccination. For immunodeficient persons, data indicate relevant waning. The extent of waning of seroprotection after yellow fever vaccination depends on age and immune status at primary vaccination.

Fatal Yellow Fever in a Kidney Transplant Patient.

A kidney-transplanted patient, unvaccinated against yellow fever (YF), developed high fever, progressed rapidly to hepatic insufficiency and coma, and died 8 days later. Real-time polymarase chain reaction for YF virus collected on the seventh day of symptoms was positive. Autopsy showed disseminated infection and midzonal hepatitis with apoptotic hepatocytes and minimal inflammatory reaction.

Viscerotropic disease and acute uveitis following yellow fever vaccination: a case report.

BACKGROUND: Yellow fever vaccine exists for over 80 years and is considered to be relatively safe. However, in rare cases it can produce serious neurotropic and viscerotropic complications. We report a case of a patient who presented both viscerotropic and neurological manifestations after yellow fever vaccination. CASE PRESENTATION: We describe the case of a 37 years old man who developed after the yellow fever vaccination a yellow fever vaccine-associated viscerotropic disease followed by acute uveitis. Prolonged detection of yellow fever RNA in blood and urine was consistent with yellow fever vaccine-associated adverse event. The final outcome was good, although with persistent fatigue over a few months. CONCLUSIONS: Even if the yellow fever vaccine is relatively safe, physicians should be aware of its possible serious adverse effects.

Travel-associated neurological disease terminated in a postmortem diagnosed atypical HSV-1 encephalitis after high-dose steroid therapy - a case report.

BACKGROUND: Human encephalitis can originate from a variety of different aetiologies, of which infection is the most common one. The diagnostic work-up is specifically challenging in patients with travel history since a broader spectrum of unfamiliar additional infectious agents, e. g. tropical disease pathogens, needs to be considered. Here we present a case of encephalitis of unclear aetiology in a female traveller returning from Africa, who in addition developed an atypical herpes simplex virus (HSV) encephalitis in close temporal relation with high-dose steroid treatment. CASE PRESENTATION: A previously healthy 48-year-old female presented with confusion syndrome and impaired vigilance which had developed during a six-day trip to The Gambia. The condition rapidly worsened to a comatose state. Extensive search for infectious agents including a variety of tropical disease pathogens was unsuccessful. As encephalitic signs persisted despite of calculated antimicrobial and antiviral therapy, high-dose corticosteroids were applied intravenously based on the working diagnosis of an autoimmune encephalitis. The treatment did, however, not improve the patient's condition. Four days later, bihemispheric signal amplification in the insular and frontobasal cortex was observed on magnetic resonance imaging (MRI). The intracranial pressure rapidly increased and could not be controlled by conservative treatment. The patient died due to tonsillar herniation 21 days after onset of symptoms. Histological examination of postmortem brain tissue demonstrated a generalized lymphocytic meningoencephalitis. Immunohistochemical reactions against HSV-1/2 indicated an atypical manifestation of herpesviral encephalitis in brain tissue. Moreover, HSV-1 DNA was detected by a next-generation sequencing (NGS) metagenomics approach. Retrospective analysis of cerebrospinal fluid (CSF) and serum samples revealed HSV-1 DNA only in specimens one day ante mortem. CONCLUSIONS: This case shows that standard high-dose steroid therapy can contribute to or possibly even trigger fulminant cerebral HSV reactivation in a critically ill patient. Thus, even if extensive laboratory diagnostics including wide-ranging search for infectious pathogens has been performed before and remained without results, continuous re-evaluation of potential differential diagnoses especially regarding opportunistic infections or reactivation of latent infections is of utmost importance, particularly if new symptoms occur.

VIO: ontology classification and study of vaccine responses given various experimental and analytical conditions.

BACKGROUND: Different human responses to the same vaccine were frequently observed. For example, independent studies identified overlapping but different transcriptomic gene expression profiles in Yellow Fever vaccine 17D (YF-17D) immunized human subjects. Different experimental and analysis conditions were likely contributed to the observed differences. To investigate this issue, we developed a Vaccine Investigation Ontology (VIO), and applied VIO to classify the different variables and relations among these variables systematically. We then evaluated whether the ontological VIO modeling and VIO-based statistical analysis would contribute to the enhanced vaccine investigation studies and a better understanding of vaccine response mechanisms. RESULTS: Our VIO modeling identified many variables related to data processing and analysis such as normalization method, cut-off criteria, software settings including software version. The datasets from two previous studies on human responses to YF-17D vaccine, reported by Gaucher et al. (2008) and Querec et al. (2009), were re-analyzed. We first applied the same LIMMA statistical method to re-analyze the Gaucher data set and identified a big difference in terms of significantly differentiated gene lists compared to the original study. The different results were likely due to the LIMMA version and software package differences. Our second study re-analyzed both Gaucher and Querec data sets but with the same data processing and analysis pipeline. Significant differences in differential gene lists were also identified. In both studies, we found that Gene Ontology (GO) enrichment results had more overlapping than the gene lists and enriched pathway lists. The visualization of the identified GO hierarchical structures among the enriched GO terms and their associated ancestor terms using GOfox allowed us to find more associations among enriched but often different GO terms, demonstrating the usage of GO hierarchical relations enhance data analysis. CONCLUSIONS: The ontology-based analysis framework supports standardized representation, integration, and analysis of heterogeneous data of host responses to vaccines. Our study also showed that differences in specific variables might explain different results drawn from similar studies.

Dependence of CD8 T Cell Response upon Antigen Load During Primary Infection : Analysis of Data from Yellow Fever Vaccination.

A major question in immunology is what role antigen load plays in determining the size of the CD8 immune response. Is the amount of antigen important during recruitment, proliferation, and/or memory formation? Animal studies have shown that antigen is only strictly required early during activation of T cells, but the importance of antigen at later timepoints is unclear. Using data from 24 volunteers infected with the yellow fever vaccine virus (YFV), we analyzed the dependence of T cell proliferation upon viral load. We found that volunteers with high viral load initially have greater T cell responses, but by 28 days post-vaccination those with lower viral load are able to 'catch-up.' Using differential equation modeling we show that this pattern is consistent with viral load only affecting recruitment (i.e., programmed proliferation) as opposed to affecting recruitment and proliferation (i.e., antigen-dependent proliferation). A quantitative understanding of the dependence of T cell dynamics on antigen load will be of use to modelers studying not only vaccination, but also cancer immunology and autoimmune disorders.

Determinants of Compliance of Travelers with Vaccination and Malaria Prophylaxis at a Travel Clinic.

BACKGROUND: Pre-travel medical consultation is essential to reduce health impairment during travel. Yellow fever vaccination (YFV) is mandatory to enter some endemic countries. In this study, we evaluated the factors that affect compliance with appropriate prevention of infectious diseases in travelers who visited clinic for YFV. METHODS: For this retrospective study, chart reviews for 658 patients who visited a travel clinic for YFV before travel were conducted. The period of this study was from January 2016 to September 2018. The associations between appropriate vaccination and factors such as travel duration, destination, time of visiting clinic before departure, and purpose of travel were analyzed. RESULTS: Among 658 patients who got YFV during the study period, 344 patients (52.3%) received additional vaccination or malaria prophylaxis following a physician's recommendation. Travelers who visited the clinic more than 21 days before departure were more compliant than those who visited 14 days or fewer before departure (odds ratio [OR], 1.90; 95% confidence interval [CI], 1.23-2.93; P = 0.004). Travelers visiting Africa were more compliant than were those traveling to South and Central America (OR, 1.97; 95% CI, 1.34-2.90; P = 0.001). Travelers in age groups of 40-49 years and over 70 years were less compliant than the 18-29 years old population (OR, 0.51; 95% CI, 0.28-0.93; P = 0.027 and OR, 0.19; 95% CI, 0.04-0.84; P = 0.03, respectively). Also, those who traveled for tour or to visit friends or relatives were more compliant than those who departed for business (OR, 0.77; 95% CI, 1.03-3.56; P = 0.04). CONCLUSION: For appropriate vaccination, pre-travel consultation at least 3 weeks before departure is crucial. Travelers should be aware of required vaccination and malaria prophylaxis before visiting South and Central America and Asia. Plans to enhance compliance of the elderly and business travelers should be contrived.

Yellow fever vaccine and risk of developing serious adverse events: a systematic review.

OBJECTIVE: To evaluate contraindications and precautions for the yellow fever vaccine (YFV) in risk populations. METHODS: A literature review was conducted by searching PubMed for "yellow fever vaccine" and "adverse events" (AEs); 207 studies were found, and 43 of them met the inclusion criteria and were included in a systematic review. RESULTS: The results for first dose of YFV in elderly patients were conflicting-some showed AEs while some showed benefits. Therefore, precaution and case-by-case decisionmaking for YFV in this population are advised. The same precautions are warranted for YFV in infants 6-8 months, with the vaccine contraindicated in those < 6 months old and safe after 9 months of age. YFV seems safe in the first trimester of pregnancy, and probably throughout gestation, as it was not associated with increased malformations. During breastfeeding, YFV continues to be controversial. The vaccine seems safe in people being treated with immunomodulatory or immunosuppressive therapy, people with immunosuppressive diseases, and solid organ and hematopoietic stem cell transplant patients; in stem cell transplants, however, a booster dose should only be applied once immunity is recovered. HlV-infected patients with a CD4+ count > 200 cells/mm3 do not have increased risk of AEs from YFV. Egg allergy vaccination protocols seem to provide a safe way to immunize these patients. CONCLUSIONS: YFV safety has been confirmed based on data from many vaccination campaigns and multiple studies. AEs seem more frequent after a first-time dose, mainly in risk groups, but this review evaluated YFV in several of the same risk groups and the vaccine was found to be safe in most of them.

Is the absence or intermittent YF vaccination the major contributor to its persistent outbreaks in eastern Africa?

Despite the availability of a safe and efficacious yellow fever vaccine since 1937, yellow fever remains a public health threat as a re-emerging disease in Africa and South America. We reviewed the trend of reported yellow fever outbreaks in eastern African countries, identified the risk epidemiological factors associated with the outbreaks and assessed the current situation of Yellow Fever vaccination in Africa. Surveillance and case finding for yellow fever in Africa are insufficient primarily due to lack of appropriate diagnostic capabilities, poor health infrastructure resulting in under-recognition, underreporting and underestimation of the disease. Despite these challenges, Ethiopia reported 302,614 cases (30,505 deaths) in 1943-2015, Kenya had 207 cases (38 deaths) in 1992-2016, Sudan experienced 31,750 suspected cases (1855 deaths) from 1940 to 2012 and Uganda had 452 cases (65 deaths) in 1941-2016. Major risk factors associated with past yellow fever outbreaks include climate, human practices and virus genetics. Comparisons between isolates from different outbreaks after 45 years have revealed the genetic stability of the structural proteins of YFV which are the primary targets of the host immune cells. This probably explains why yellow fever 17D vaccine is considered as outstandingly efficacious and safe after being used for 75 years. However, the 14 amino-acid changes among these isolates may have a greater impact on the changing disease epidemiology, virulence and transmission rate. Low population immunity against YF influences outbreak frequency especially in countries where the incorporation of YF vaccination is not combined with mass vaccination campaigns or vaccination is limited to international travellers. Understanding Yellow fever virus epidemiology as determined by its evolution underscores appropriate disease mitigation strategies and immunization policies. Mobilizing scarce resources to enhance population immunity through sufficient vaccination, promoting environmental sanitation/hygienic practices, driving behavioral change and community-based vector control are significant to preventing future epidemics.

Yellow fever vaccine-associated neurotropic disease (YEL-AND) - A case report.

Yellow fever (YF) is a mosquito-borne viral hemorrhagic fever, which is a serious and potentially fatal disease with no specific antiviral treatment that can be effectively prevented by an attenuated vaccine (YEL). Despite the long history of safe and efficacious YF vaccination, sporadic case reports of serious adverse events (SAEs) have been reported, including yellow fever vaccine-associated neurotropic disease (YEL-AND). YEL-AND usually appears within one month of YF vaccination, manifesting as meningoencephalitis, Guillain-Barré syndrome (GBS) or acute disseminated encephalomyelitis (ADEM). We report a case of YEL-AND with meningitis presentation in a 39-year-old Caucasian man without evidence of significant risk factors, which was confirmed by the presence of the YF virus and specific immunoglobulin G (IgG) antibodies in the cerebrospinal fluid (CSF). In conclusion, we should stress the importance of balancing the risk of SAEs associated with the vaccine and the benefits of YF vaccination for each patient individually.

Immunogenicity of Yellow Fever Vaccine Coadministered With MenAfriVac in Healthy Infants in Ghana and Mali.

BACKGROUND: Yellow fever (YF) is still a major public health problem in endemic regions of Africa and South America. In Africa, one of the main control strategies is routine vaccination within the Expanded Programme on Immunization (EPI). A new meningococcal A conjugate vaccine (PsA-TT) is about to be introduced in the EPI of countries in the African meningitis belt, and this study reports on the immunogenicity of the YF-17D vaccines in infants when administered concomitantly with measles vaccine and PsA-TT. METHODS: Two clinical studies were conducted in Ghana and in Mali among infants who received PsA-TT concomitantly with measles and YF vaccines at 9 months of age. YF neutralizing antibody titers were measured using a microneutralization assay. RESULTS: In both studies, the PsA-TT did not adversely affect the immune response to the concomitantly administered YF vaccine at the age of 9 months. The magnitude of the immune response was different between the 2 studies, with higher seroconversion and seroprotection rates found in Mali vs Ghana. CONCLUSIONS: Immunogenicity to YF vaccine is unaffected when coadministered with PsA-TT at 9 months of age. Further studies are warranted to better understand the determinants of the immune response to YF vaccine in infancy. CLINICAL TRIALS REGISTRATION: ISRCTN82484612 (PsA-TT-004); PACTR201110000328305 (PsA-TT-007).

Egg allergy and yellow fever vaccination.

OBJECTIVE: Evaluate biomarkers capable of safely guiding Yellow fever vaccine (YFV) vaccination among individuals suspicious of hen's egg allergy, and identify factors associated with a higher risk for adverse events after immunization (AEAI). METHODS: Patients underwent skin prick test (SPT) for standardized allergens: whole egg, egg white, egg yolk; YFV (1:10 dilution; Biomanguinhos-Fiocruz), and intradermal test (IDT; YFV 0.02 mL, 1:100 dilution) and positive and negative controls. Serum levels of specific IgE (sIgE) for a whole egg, egg white, egg yolk, egg albumin, ovomucoid, lysozyme, and conalbumin (ImmunoCap®; ThermoFisher®) were obtained. Patients sensitized to YFV were submitted to YFV desensitization, and those negatives received YFV (0.5mL) and remained under surveillance for at least one hour. RESULTS: 103 patients were enrolled, 95% under 12 years old. 71% (81/103) of patients had reactions: 80% immediate, 11% mixed, and 9% delayed. There was an association between positive skin test results with YFV and the severity of the reaction (OR:7.64; 95%CI:1.61-36.32; p = 0,011). Only the presence of sIgE to ovomucoid was associated with clinical symptoms (p = 0,025). Thirty patients underwent the YFV desensitization protocol. CONCLUSION: There is a relationship between the positivity of the egg's components and the severity of the clinical reaction. Furthermore, the relationship between the positivity of the tests with the YFV and egg's components may show a tendency to look at ovomucoid and conalbumin, but it is not a certainty. Therefore, further studies are needed to confirm these associations, and for now, the authors still recommend using the vaccine for testing when necessary.

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).

Impact of HIV-Related Immune Impairment of Yellow Fever Vaccine Immunogenicity in People Living with HIV-ANRS 12403.

The yellow fever (YF) vaccine is one of the safest and most effective vaccines currently available. Still, its administration in people living with HIV (PLWH) is limited due to safety concerns and a lack of consensus regarding decreased immunogenicity and long-lasting protection for this population. The mechanisms associated with impaired YF vaccine immunogenicity in PLWH are not fully understood, but the general immune deregulation during HIV infection may play an important role. To assess if HIV infection impacts YF vaccine immunogenicity and if markers of immune deregulation could predict lower immunogenicity, we evaluated the association of YF neutralization antibody (NAb) titers with the pre-vaccination frequency of activated and exhausted T cells, levels of pro-inflammatory cytokines, and frequency of T cells, B cells, and monocyte subsets in PLWH and HIV-negative controls. We observed impaired YF vaccine immunogenicity in PLWH with lower titers of YF-NAbs 30 days after vaccination, mainly in individuals with CD4 count <350 cells/mm3. At the baseline, those individuals were characterized by having a higher frequency of activated and exhausted T cells and tissue-like memory B cells. Elevated levels of those markers were also observed in individuals with CD4 count between 500 and 350 cells/mm3. We observed a negative correlation between the pre-vaccination level of CD8+ T cell exhaustion and CD4+ T cell activation with YF-NAb titers at D365 and the pre-vaccination level of IP-10 with YF-NAb titers at D30 and D365. Our results emphasize the impact of immune activation, exhaustion, and inflammation in YF vaccine immunogenicity in PLWH.

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.

Persistence of yellow fever vaccine-induced antibodies after solid organ transplantation.

Immunization using live attenuated vaccines represents a contra-indication after solid organ transplantation (SOT): consequently, transplant candidates planning to travel in countries where yellow fever is endemic should be vaccinated prior to transplantation. The persistence of yellow fever vaccine-induced antibodies after transplantation has not been studied yet. We measured yellow-fever neutralizing antibodies in 53 SOT recipients vaccinated prior to transplantation (including 29 kidney recipients and 18 liver recipients). All but one (98%) had protective titers of antibodies after a median duration of 3 years (min.: 0.8, max.: 21) after transplantation. The median antibody level was 40 U/L (interquartile range: 40-80). For the 46 patients with a known or estimated date of vaccination, yellow-fever antibodies were still detectable after a median time of 13 years (range: 2-32 years) post-immunization. Our data suggest there is long-term persistence of antibodies to yellow fever in SOT recipients who have been vaccinated prior to transplantation.