Live vaccinations in dermatology for immunosuppressed patients: a narrative review.

Given the higher susceptibility to infectious disease in patients receiving immunosuppressive therapies for inflammatory dermatologic conditions, immunization is important in this population. While live vaccines protect against life-threatening diseases, they can be harmful in immunosuppressed patients given the risk of replication of the attenuated pathogen and adverse reactions. The utilization of live vaccines in immunosuppressed patients depends on multiple factors such as the vaccine and therapy regimen. To provide an overview of evidence-based recommendations for the use of live vaccines in patients receiving immunosuppressive therapies for dermatological conditions. A literature search of the PubMed database was performed using keywords live vaccine, live-attenuated vaccine, dermatology, immunosuppressed, and immunocompromised, and specific immunosuppressive therapies: corticosteroids, glucocorticoids, methotrexate, azathioprine, cyclosporine, mycophenolate mofetil, biologics. Relevant articles written in English were included. Using these keywords, 125 articles were reviewed, of which 28 were ultimately selected. Recommendations for live vaccines can be determined on a case-by-case basis. Measles, mumps, rubella, varicella (MMRV) vaccines may be safely administered to patients on low-dose immunosuppressive agents while the yellow fever vaccine is typically contraindicated. It may be safe to administer live MMRV boosters to children on immunosuppressive therapies and the live herpes zoster vaccine to patients on biologics. Given poor adherence to immunization guidelines in immunosuppressed patients, dermatologists have a critical role in educating patients and general practitioners regarding live vaccines. By reviewing a patient's vaccination history and following immunization guidelines prior to initiating immunosuppressive therapies, physicians can mitigate morbidity and mortality from vaccine-preventable diseases.

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.

Comparing immunogenicity and protective efficacy of the yellow fever 17D vaccine in mice.

The live-attenuated yellow fever 17D (YF17D) vaccine is one of the most efficacious human vaccines and also employed as a vector for novel vaccines. However, in the lack of appropriate immunocompetent small animal models, mechanistic insight in YF17D-induced protective immunity remains limited. To better understand YF17D vaccination and to identify a suitable mouse model, we evaluated the immunogenicity and protective efficacy of YF17D in five complementary mouse models, i.e. wild-type (WT) BALB/c, C57BL/6, IFN-α/ß receptor (IFNAR-/-) deficient mice, and in WT mice in which type I IFN signalling was temporally ablated by an IFNAR blocking (MAR-1) antibody. Alike in IFNAR-/- mice, YF17D induced in either WT mice strong humoral immune responses dominated by IgG2a/c isotype (Th1 type) antibodies, yet only when IFNAR was blocked. Vigorous cellular immunity characterized by CD4+ T-cells producing IFN-γ and TNF-α were mounted in MAR-1 treated C57BL/6 and in IFNAR-/- mice. Surprisingly, vaccine-induced protection was largely mouse model dependent. Full protection against lethal intracranial challenge and a massive reduction of virus loads was conferred already by a minimal dose of 2 PFU YF17D in BALB/c and IFNAR-/- mice, but not in C57BL/6 mice. Correlation analysis of infection outcome with pre-challenge immunological markers indicates that YFV-specific IgG might suffice for protection, even in the absence of detectable levels of neutralizing antibodies. Finally, we propose that, in addition to IFNAR-/- mice, C57BL/6 mice with temporally blocked IFN-α/ß receptors represent a promising immunocompetent mouse model for the study of YF17D-induced immunity and evaluation of YF17D-derived vaccines.

Yellow fever vaccine protects mice against Zika virus infection.

Zika virus (ZIKV) emerged as an important infectious disease agent in Brazil in 2016. Infection usually leads to mild symptoms, but severe congenital neurological disorders and Guillain-Barré syndrome have been reported following ZIKV exposure. Creating an effective vaccine against ZIKV is a public health priority. We describe the protective effect of an already licensed attenuated yellow fever vaccine (YFV, 17DD) in type-I interferon receptor knockout mice (A129) and immunocompetent BALB/c and SV-129 (A129 background) mice infected with ZIKV. YFV vaccination provided protection against ZIKV, with decreased mortality in A129 mice, a reduction in the cerebral viral load in all mice, and weight loss prevention in BALB/c mice. The A129 mice that were challenged two and three weeks after the first dose of the vaccine were fully protected, whereas partial protection was observed five weeks after vaccination. In all cases, the YFV vaccine provoked a substantial decrease in the cerebral viral load. YFV immunization also prevented hippocampal synapse loss and microgliosis in ZIKV-infected mice. Our vaccine model is T cell-dependent, with AG129 mice being unable to tolerate immunization (vaccination is lethal in this mouse model), indicating the importance of IFN-γ in immunogenicity. To confirm the role of T cells, we immunized nude mice that we demonstrated to be very susceptible to infection. Immunization with YFV and challenge 7 days after booster did not protect nude mice in terms of weight loss and showed partial protection in the survival curve. When we evaluated the humoral response, the vaccine elicited significant antibody titers against ZIKV; however, it showed no neutralizing activity in vitro and in vivo. The data indicate that a cell-mediated response promotes protection against cerebral infection, which is crucial to vaccine protection, and it appears to not necessarily require a humoral response. This protective effect can also be attributed to innate factors, but more studies are needed to strengthen this hypothesis. Our findings open the way to using an available and inexpensive vaccine for large-scale immunization in the event of a ZIKV outbreak.

Immunogenicity and safety of primary fractional-dose yellow fever vaccine in autoimmune rheumatic diseases.

BACKGROUND: Brazil faced a yellow fever(YF) outbreak in 2016-2018 and vaccination was considered for autoimmune rheumatic disease patients(ARD) with low immunosuppression due to YF high mortality. OBJECTIVE: This study aimed to evaluate, prospectively for the first time, the short-term immunogenicity of the fractional YF vaccine(YFV) immunization in ARD patients with low immunossupression. METHODS AND RESULTS: A total of 318 participants(159 ARD and 159 age- and sex-matched healthy controls) were vaccinated with the fractional-dose(one fifth) of 17DD-YFV. All subjects were evaluated at entry(D0), D5, D10, and D30 post-vaccination for clinical/laboratory and disease activity parameters for ARD patients. Post-vaccination seroconversion rate(83.7%vs.96.6%, p = 0.0006) and geometric mean titers(GMT) of neutralizing antibodies[1143.7 (95%CI 1012.3-1292.2) vs.731 (95%CI 593.6-900.2), p<0.001] were significantly lower in ARD compared to controls. A lower positivity rate of viremia was also identified for ARD patients compared to controls at D5 (53%vs.70%, p = 0.005) and the levels persisted in D10 for patients and reduced for controls(51%vs.19%, p = 0.0001). The viremia was the only variable associated with seroconvertion. No serious adverse events were reported. ARD disease activity parameters remained stable at D30(p>0.05). CONCLUSION: Fractional-dose 17DD-YF vaccine in ARD patients resulted in a high rate of seroconversion rate(>80%) but lower than controls, with a longer but less intense viremia. This vaccine was immunogenic, safe and did not induce flares in ARD under low immunosuppression and may be indicated in YF outbreak situations and for patients who live or travel to endemic areas. TRIAL REGISTRATION: This clinical trial was registered with Clinicaltrials.gov (#NCT03430388).

[Recrudescence of yellow fever in Chad: case report of the last confirmed case in the health district of Lai-Chad]. / Recrudescence de la fièvre jaune au Tchad: à propos du dernier cas confirmé dans le district sanitaire de Lai-Tchad.

Yellow fever (YF) is a viral haemorrhagic fever caused by yellow fever virus transmitted by Aedes mosquitoes. Since 2013, in Chad, four cases of yellow fever have been detected and confirmed as part of the national fever surveillance program. We here report the last clinical case confirmed in the health district of Lai. The patient was a 57-year-old man with no significant medical and surgical history and unknown immunisation status. He consulted on April 21st, 2020 for fever, moderate to low abundance jaundice and epistaxis (nosebleed) and painful hepatomegaly. Paraclinical examinations, such as RT-PCR, objectified yellow fever virus in post-mortem tissue sample. Thus, confirmed yellow fever cases in this district, the low level of vaccination coverage, the circulation of the virus and the presence of vector in the country should warn of a real threat of reemergence of yellow fever in Chad.

Safety and immunogenicity of Vi-typhoid conjugate vaccine co-administration with routine 9-month vaccination in Burkina Faso: A randomized controlled phase 2 trial.

OBJECTIVES: In 2017, the World Health Organisation (WHO) pre-qualified a single-dose typhoid conjugate vaccine (TCV) and identified TCV co-administration studies as a research priority. Accordingly, we tested co-administration of Typbar TCV® (Bharat Biotech International) with measles-rubella (MR) and yellow fever (YF) vaccines. METHODS: We conducted a randomized, double-blind, and controlled, phase 2 trial in Ouagadougou, Burkina Faso. Healthy children aged 9-11 months were randomized 1:1 to receive TCV (Group 1) or control vaccine (inactivated polio vaccine (IPV), Group 2). Vaccines were administered intramuscularly with routine MR and YF vaccines. Safety was assessed by (1) local and systemic reactions on days 0, 3, and 7; (2) unsolicited adverse events within 28 days; and (3) serious adverse events (SAEs) within six months after immunization. RESULTS: We enrolled, randomized, and vaccinated 100 eligible children (49 Group 1 and 51 Group 2). Safety outcomes occurred with similar frequency in both groups: local/solicited reactions (Group 1: 1/49, Group 2: 3/50), systemic/solicited reactions (Group 1: 4/49, Group 2: 9/50), unsolicited adverse events (Group 1: 26/49, Group 2: 33/51), and SAEs (Group 1: 2/49, Group 2: 3/51). TCV conferred robust immunogenicity without interference with MR or YF vaccines. CONCLUSION: TCV can be safely co-administered with MR and YF vaccines to children at the 9-month vaccination visit.

Serum biomarker profile orchestrating the seroconversion status of patients with autoimmune diseases upon planned primary 17DD Yellow fever vaccination.

The present study aimed to investigate whether the serum biomarkers of immune response orchestrate the seroconversion status in patients with autoimmune diseases (AID) upon planned primary 17DD-YF vaccination. For this purpose a total of 161 individuals were enrolled in a prospective study, including patients with Rheumatoid Arthritis (RA = 38), Spondyloarthritis (SpA = 51), Systemic Lupus Erythematosus (SLE = 21) and Sjögren's Syndrome (SS = 30) along with a group of healthy controls (HC = 21). Analysis of plaque reduction neutralization test (PRNT) titers and seropositivity rates along with the 17DD-YF viremia and serum biomarkers were carried out at distinct time points (D0/D3-4/D5-6/D7/D14-28). The results demonstrated an overall lower PRNT titer and seropositivity rate (170 vs. 448; 77 vs. 95%) in AID as compared to HC, especially in SpA and SLE subgroups. No significant differences were observed in the viremia levels amongst groups. In general, a more prominent serum biomarker response was observed in AID as compared to HC, throughout the timeline kinetics. Remarkably, AID/PRNT(-) exhibited higher levels of several biomarkers at baseline as compared to AID/PRNT+. Moreover, while AID/PRNT(+) exhibited earlier increase in serum biomarkers at D3-4/D5-6, the AID/PRNT(-) displayed higher response at later time points (D7/D14-D28). Of note, a synchronic increase of IFN-γ at the peak of viremia (D5-6) was observed in HC and AID/PRNT(+) groups, whereas a later asynchronous IFN-γ response was reported for AID/PRNT(-) at D7. The biomarker profile tends to deflate at post-vaccination timeline, highlighting a putative immunomodulatory effect of live attenuated 17DD-YF vaccine in AID/PRNT(+), but not in AID/PRNT(-). Altogether these data suggested that inflammatory status prior vaccination, low IFN-γ at viremia peak and the occurrence of asynchronous biomarker storm after 17DD-YF vaccination may orchestrate the lack of neutralizing antibody response γ.

Immunogenicity and duration of protection after yellow fever vaccine in people living with human immunodeficiency virus: a systematic review.

BACKGROUND: We lack the rationale on which to base the development of a yellow fever (YF) vaccination schedule for people living with human immunodeficiency virus (PLWHIV). OBJECTIVES: To report on the current evidence regarding the seroconversion rate and the duration of humoral protection after YF vaccine, as well as the impact of revaccination in PLWHIV. DATA SOURCES: MEDLINE, Google Scholar, LILACS and Cochrane CENTRAL were searched. METHODS: We selected studies on PLWHIV of all ages (including perinatally HIV-infected patients) and all settings (YF endemic and non-endemic zones). Intervention investigated was vaccination against YF, at least once after the HIV diagnosis. The research questions were the seroconversion rate, duration of humoral immunity after YF vaccine and impact of revaccination in PLWHIV. Selected studies were assessed for quality using the Newcastle-Ottawa scale. RESULTS: Ten, six and six studies were selected for the systematic review of each question, respectively. Only one study addressed the first question in perinatally HIV-infected children. The quality of the studies was assessed as Poor (n = 16), Fair (n = 2) or Good (n = 4). A meta-analysis demonstrated that 97.6% (95% CI 91.6%-100%) of the included population seroconverted. Between 1 and 10 years after YF vaccine, reported persistence of neutralizing antibodies was 72% (95% CI 53.6%-91%), and it was 62% (95% CI 45.4%-78.6%) more than 10 years after YF vaccine. No conclusions could be drawn on impact of revaccination because of the small number of patients. CONCLUSIONS: The current evidence regarding seroconversion rate, duration of humoral protection after YF vaccine and impact of revaccination in PLWHIV is limited by the low number and quality of studies. Based on the presently available data, it is difficult to rationally develop yellow fever vaccination guidelines for PLWHIV.

Incidence, drivers and global health implications of the 2019/2020 yellow fever sporadic outbreaks in Sub-Saharan Africa.

The 2019 and 2020 sporadic outbreaks of yellow fever (YF) in Sub-Saharan African countries had raised a lot of global health concerns. This article aims to narratively review the vector biology, YF vaccination program, environmental factors and climatic changes, and to understand how they could facilitate the reemergence of YF. This study comprehensively reviewed articles that focused on the interplay and complexity of YF virus (YFV) vector diversity/competence, YF vaccine immunodynamics and climatic change impacts on YFV transmission as they influence the 2019/2020 sporadic outbreaks in Sub-Saharan Africa (SSA). Based on available reports, vectorial migration, climatic changes and YF immunization level could be reasons for the re-mergence of YF at the community and national levels. Essentially, the drivers of YFV infection due to spillover are moderately constant. However, changes in land use and landscape have been shown to influence sylvan-to-urban spillover. Furthermore, increased precipitation and warmer temperatures due to climate change are likely to broaden the range of mosquitoes' habitat. The 2019/2020 YF outbreaks in SSA is basically a result of inadequate vaccination campaigns, YF surveillance and vector control. Consequently, and most importantly, adequate immunization coverage must be implemented and properly achieved under the responsibility of the public health stakeholders.

Adverse events following yellow fever vaccination in immunocompromised persons.

This observational retrospective study conducted during an yellow fever (YF) outbreak in Sao Paulo, Brazil, in 2017-2018, describes adverse events (AE) following YF vaccination of immunocompromised persons. Risks and benefits of vaccination were individually evaluated by physicians. AE were assessed by phone call or electronic mail, 14 to 90 days after vaccination. Three hundred and eighty one immunocompromised persons received a full-dose of YF vaccine. Their age ranged from 1.4 to 89.3 years (median 50.8 years); 53% were women; 178 (46.7%) had chronic kidney disease, 78 (20.5%) had immune-mediated inflammatory diseases; 94 (24.7%) were using or had recently used immunosuppressive/ immunomodulatory drugs. All of them denied previous YF vaccination. We were able to contact 341 (89.5%) vaccinees: 233 (68.3%) of them received the YF vaccine from BioManguinhos and 108 (31.7%) received the vaccine from Sanofi-Pasteur; 130 (38.1%) vaccinees received other vaccines (up to 4) simultaneously with the the YF vaccine, mostly hepatitis B (59 vaccinees), pneumococcal polysaccharide 23-valent (46), influenza (43) and diphtheria-tetanus (dT, 41). One hundred and eleven vaccinees (32.6%) reported at least one AE: 79 (23.2%) presented systemic AE, 44 (12.9%) had local AE and 12 had both, local and systemic AE. The most common AE was pain at the injection site (41 persons, 12%), myalgia (34; 10%), fever (25; 7.3%) and headache (16; 4.7%). There was no statistically significant difference on the AE frequency according to the vaccine producer. There were four severe AE: one hospitalization and three deaths, considered not related to the YF vaccine.

Yellow Fever Vaccine Administration at Global TravEpiNet (GTEN) Clinics during a Period of Limited Vaccine Availability in the United States, 2017-2018.

In 2016, Sanofi Pasteur (S-P) experienced a manufacturing disruption of YF-Vax, the only U.S.-licensed yellow fever vaccine depleting the U.S. supply by mid-2017. Sanofi Pasteur received approval to import Stamaril, S-P's French-manufactured yellow fever vaccine, for use in 260 U.S. civilian clinics under an Expanded Access Program (EAP). The CDC also broadened its yellow fever vaccination indication in early 2018. Our objective was to assess usage at participating Global TravEpiNet (GTEN) clinics, a U.S. CDC-supported national consortium of clinical sites that administer vaccines, during this period of limited availability and changing recommendations. We analyzed 2012-2018 GTEN data for yellow fever vaccine usage, unavailability, and reasons for refusal. We also performed a brief voluntary survey of GTEN sites to better understand their experience during the shortage. YF-Vax unavailability at certain GTEN clinics was intermittent and recurrent, starting months before total depletion. Unavailability at GTEN clinics peaked weeks before the total depletion. Compared with historic norms, yellow fever vaccine usage following initial vaccine availability limitations did not change until vaccine recommendations were broadened. Refusal of recommended yellow fever vaccine also decreased during this period. Queried sites participating in the EAP felt their supply of vaccine was adequate. Our analysis suggests that in response to depletion of a travel vaccine, an EAP can make an unlicensed product available, patients will participate in such a program, and the program can respond to expanding recommendations for vaccine usage.

Immunogenicity and safety of fractional doses of yellow fever vaccines: a randomised, double-blind, non-inferiority trial.

BACKGROUND: Stocks of yellow fever vaccine are insufficient to cover exceptional demands for outbreak response. Fractional dosing has shown efficacy, but evidence is limited to the 17DD substrain vaccine. We assessed the immunogenicity and safety of one-fifth fractional dose compared with standard dose of four WHO-prequalified yellow fever vaccines produced from three substrains. METHODS: We did this randomised, double-blind, non-inferiority trial at research centres in Mbarara, Uganda, and Kilifi, Kenya. Eligible participants were aged 18-59 years, had no contraindications for vaccination, were not pregnant or lactating, had no history of yellow fever vaccination or infection, and did not require yellow fever vaccination for travel. Eligible participants were recruited from communities and randomly assigned to one of eight groups, corresponding to the four vaccines at standard or fractional dose. The vaccine was administered subcutaneously by nurses who were not masked to treatment, but participants and other study personnel were masked to vaccine allocation. The primary outcome was proportion of participants with seroconversion 28 days after vaccination. Seroconversion was defined as post-vaccination neutralising antibody titres at least 4 times pre-vaccination measurement measured by 50% plaque reduction neutralisation test (PRNT50). We defined non-inferiority as less than 10% decrease in seroconversion in fractional compared with standard dose groups 28 days after vaccination. The primary outcome was measured in the per-protocol population, and safety analyses included all vaccinated participants. This trial is registered with ClinicalTrials.gov, NCT02991495. FINDINGS: Between Nov 6, 2017, and Feb 21, 2018, 1029 participants were assessed for inclusion. 69 people were ineligible, and 960 participants were enrolled and randomly assigned to vaccine manufacturer and dose (120 to Bio-Manguinhos-Fiocruz standard dose, 120 to Bio-Manguinhos-Fiocruz fractional dose, 120 to Chumakov Institute of Poliomyelitis and Viral Encephalitides standard dose, 120 to Chumakov Institute of Poliomyelitis and Viral Encephalitides fractional dose, 120 to Institut Pasteur Dakar standard dose, 120 to Institut Pasteur Dakar fractional dose, 120 to Sanofi Pasteur standard dose, and 120 to Sanofi Pasteur fractional dose). 49 participants had detectable PRNT50 at baseline and 11 had missing PRNT50 results at baseline or 28 days. 900 were included in the per-protocol analysis. 959 participants were included in the safety analysis. The absolute difference in seroconversion between fractional and standard doses by vaccine was 1·71% (95% CI -2·60 to 5·28) for Bio-Manguinhos-Fiocruz, -0·90% (-4·24 to 3·13) for Chumakov Institute of Poliomyelitis and Viral Encephalitides, 1·82% (-2·75 to 5·39) for Institut Pasteur Dakar, and 0·0% (-3·32 to 3·29) for Sanofi Pasteur. Fractional doses from all four vaccines met the non-inferiority criterion. The most common treatment-related adverse events were headache (22·2%), fatigue (13·7%), myalgia (13·3%) and self-reported fever (9·0%). There were no study-vaccine related serious adverse events. INTERPRETATION: Fractional doses of all WHO-prequalified yellow fever vaccines were non-inferior to the standard dose in inducing seroconversion 28 days after vaccination, with no major safety concerns. These results support the use of fractional dosage in the general adult population for outbreak response in situations of vaccine shortage. FUNDING: The study was funded by Médecins Sans Frontières Foundation, Wellcome Trust (grant no. 092654), and the UK Department for International Development. Vaccines were donated in kind.

The search for yellow fever virus vaccine in breast milk of inadvertently vaccinated women in Brazil.

Eleven lactating women were inadvertently vaccinated with 17DD yellow fever vaccine in a small city of Sao Paulo State, Brazil. Their infants were being exclusively breast-fed and the breastfeeding was interrupted for 10 days. Serum and breastmilk were collected from the vaccinated mothers and tested for the presence of genomic RNA of the vaccine strain 8, 10 and 15 days after vaccination. Viral RNA was not detected in any of the serum and human milk samples tested and the infants remained asymptomatic. Our result strengthens the effectineness of stopping breastfeeding for 10 days after the inadvertent yellow fever vaccination of lactating women.

Eliminating yellow fever epidemics in Africa: Vaccine demand forecast and impact modelling.

BACKGROUND: To counter the increasing global risk of Yellow fever (YF), the World Health Organisation initiated the Eliminate Yellow fever Epidemics (EYE) strategy. Estimating YF burden, as well as vaccine impact, while accounting for the features of urban YF transmission such as indirect benefits of vaccination, is key to informing this strategy. METHODS AND FINDINGS: We developed two model variants to estimate YF burden in sub-Saharan Africa, assuming all infections stem from either the sylvatic or the urban cycle of the disease. Both relied on an ecological niche model fitted to the local presence of any YF reported event in 34 African countries. We calibrated under-reporting using independent estimates of transmission intensity provided by 12 serological surveys performed in 11 countries. We calculated local numbers of YF infections, deaths and disability-adjusted life years (DALYs) lost based on estimated transmission intensity while accounting for time-varying vaccination coverage. We estimated vaccine demand and impact of future preventive mass vaccination campaigns (PMVCs) according to various vaccination scenarios. Vaccination activities conducted in Africa between 2005 and 2017 were estimated to prevent from 3.3 (95% CI 1.2-7.7) to 6.1 (95% CI 2.4-13.2) millions of deaths over the lifetime of vaccinees, representing extreme scenarios of none or maximal herd effects, respectively. By prioritizing provinces based on the risk of urban YF transmission in future PMVCs, an average of 37.7 million annual doses for PMVCs over eight years would avert an estimated 9,900,000 (95% CI 7,000,000-13,400,000) infections and 480,000 (180,000-1,140,000) deaths over the lifetime of vaccinees, corresponding to 1.7 (0.7-4.1) deaths averted per 1,000 vaccine doses. CONCLUSIONS: By estimating YF burden and vaccine impact over a range of spatial and temporal scales, while accounting for the specificity of urban transmission, our model can be used to inform the current EYE strategy.

Yellow Fever Vaccine Safety Perception of Pregnant Women in Emergency Response Mass Vaccination in Uganda.

Yellow fever vaccine, a live attenuated vaccine, is primarily administered to pregnant women during outbreaks. A qualitative study was conducted in pregnant women on the perception of yellow fever mass vaccination. In total, interviews with 20 women-13 semi-structured interviews and one focus group discussion with seven participants-were analyzed. This study showed that conflicting information about vaccine safety led to concern about miscarriage. Furthermore, it was believed that vaccination during gestation would concurrently immunize the fetus by transplacental antibody transfer. Consultation of health workers at the vaccination site led to diverse recommendations. When vaccinating pregnant women, clear health communication is crucial. Vaccine recommendations should be obeyed, and health workers should be trained to address emerging vaccine concerns. Pregnant women should be informed that a booster dose is recommended to achieve lifelong immunity. After pregnancy, a booster should be offered to women in endemic areas.

Factors associated with severity of adverse events following yellow fever vaccination during the biggest outbreak of the disease recorded in Brazil, 2016-2017. / Fatores associados à gravidade dos eventos adversos pós-vacinação contra a febre amarela durante o maior surto da doença registrado no Brasil, 2016-2017.

OBJECTIVE: to analyze characteristics, incidence and factors associated with serious adverse events (SAEs) following yellow fever vaccination during an outbreak of the disease in Brazil (2016-2017). METHODS: this was a case-control study using data from the National Immunization Program Information System (SI-PNI); SAE were considered to be cases, and non-serious adverse events (NSAE) were considered to be controls. RESULTS: we analyzed 135 SAE cases and 1,058 controls; of the 135 SAE, 79 (58.5%) were males and median age was 28 years [09-49]; incidence in January 2017 reached 1.3 case per 100,000 vaccine doses administered; there was statistical association with males (Odds Ratio [OR]=1.73 - 95%CI 1.20;2.48), primary vaccination (OR=1.65 - 95%CI 1.01;2.71), and being 60 years of age or older taking as reference those aged under 5 (OR=4.4; p-value <0.02). CONCLUSION: SAE owing to yellow fever vaccine showed a greater chance of occurring in men, the elderly and primary vaccination.

Longitudinal dynamics of the human B cell response to the yellow fever 17D vaccine.

A comprehensive understanding of the development and evolution of human B cell responses induced by pathogen exposure will facilitate the design of next-generation vaccines. Here, we utilized a high-throughput single B cell cloning technology to longitudinally track the human B cell response to the yellow fever virus 17D (YFV-17D) vaccine. The early memory B cell (MBC) response was mediated by both classical immunoglobulin M (IgM) (IgM+CD27+) and switched immunoglobulin (swIg+) MBC populations; however, classical IgM MBCs waned rapidly, whereas swIg+ and atypical IgM+ and IgD+ MBCs were stable over time. Affinity maturation continued for 6 to 9 mo following vaccination, providing evidence for the persistence of germinal center activity long after the period of active viral replication in peripheral blood. Finally, a substantial fraction of the neutralizing antibody response was mediated by public clones that recognize a fusion loop-proximal antigenic site within domain II of the viral envelope glycoprotein. Overall, our findings provide a framework for understanding the dynamics and complexity of human B cell responses elicited by infection and vaccination.

Yellow Fever Vaccination In EGG-Allergic Children.

Yellow fever vaccine contains ovalbumin, and guidelines for vaccination of egg allergic patients vary widely. We present our experience of administering yellow fever vaccine to 11 egg-allergic children, including 3 with anaphylaxis to egg, in 2 Australian tertiary pediatric hospitals. There was variation in the vaccination protocols used; however, all patients were successfully vaccinated and no serious adverse events were reported.

Minimal immune response to booster vaccination against Yellow Fever associated with pre-existing antibodies.

Ever since its development in the 1930's, the live-attenuated Yellow Fever virus vaccine YF-17D has been highly effective. Despite the increasing knowledge on the immune biology of the YF-17D vaccine, most studies have focused only on a few types of immune cells and pathways or mainly on the primary adaptive immune response to YF-17D vaccination. Here, we examined humoral, innate and adaptive cellular responses in a longitudinal YF-17D vaccination study in Switzerland, comparing both primary and booster vaccination. In contrast to the strong innate and adaptive immune response to the primary vaccination, we find that the response to boosting is much reduced. Our data show an inverse association of neutralizing antibodies at baseline with vaccine virus replication and with the immune response upon boosting. These results suggest that booster vaccination may not have major immunological effects when neutralizing antibodies are present. Importantly, our study population was healthy adults in a non-endemic country and ultimately booster vaccine requirement must be assessed based on additional epidemiological and public health considerations in endemic areas.