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Epidemic vector-borne viral infections pose a serious threat to public health worldwide. There is currently no specific preventive treatment for most of them. One of the promising solutions for combating viral fevers is development of vector vaccines, including MVA-based vaccines, which have virtually no adverse side effects. The safety of the MVA strain and absent reactogenicity of recombinant MVA vaccines have been supported by many clinical trials.The article focuses on test results for similar preventive products against viral fevers: Crimean-Congo hemorrhagic fever, Rift Valley fever, yellow fever, Chikungunya and Zika fevers.Their immunogenicity was evaluated on immunocompetent and immunocompromised white mice; their protective efficacy was assessed on immunocompromised white mice deficient in IFN-α/β receptors, that are used for experimental modeling of the infection. Nearly all the new recombinant vaccines expressing immunodominant antigens demonstrated 100% protective efficacy. It has been found that although the vaccine expressing Zika virus structural proteins induced antibodies against specific viral glycoproteins, it can be associated with high risks when used for prevention of Zika fever in individuals who had dengue fever in the past, due to the phenomenon known as antibody-dependent enhancement of infection, which can occur in diseases caused by antigenically related flaviruses. For this reason, the vaccine expressing non-structural protein 1 (NS1) was developed for vaccination against Zika fever.The yellow fever vaccine developed on the MVA platform had immunogenicity similar to that of the commercial 17D vaccine, outperforming the latter in safety.

In the late 1930s, the 17D vaccine against yellow fever was produced in record time. 17D was and is an excellent vaccine. Its rapid diffusion led, however, to several problems, the most important among them being the 1942 massive contamination of the vaccine distributed to the US Army by the hepatitis B virus. The US part of this story is relatively well-known, but its Brazilian part much less so. In 1940, scientists who were producing the 17D vaccine in Rio de Janeiro found that it was contaminated by an “icterus virus” that originated in normal human serum. They solved this problem through the exclusion of human serum from vaccine production, but failed to persuade their US colleagues to do the same. The Rio experts, aware of the potential pitfalls of a new technology, carefully supervised the consequences of their vaccination campaigns. They were thus able to rapidly spot problems and eliminate them. By contrast, US scientists, persuaded of their technical superiority and distrustful of warnings that originated from a “less developed” country, neglected to implement basic public health rules. A major disaster followed. (Am J Public Health. 2021;111(9): 1654–1660. https://doi.org/10.2105/AJPH.2021.306313 )

Introduction The COVID-19 pandemic is a globalized health concern caused by a beta-coronavirus named Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). Since December 2019, when this outbreak flared in Wuhan, China, COVID-19 cases have been continuously rising all over the world. Due to the emergence of SARS-CoV-2 mutants, subsequent waves are flowing in a faster manner as compared to the primary wave, which is more contagious and causing higher mortality. Recently, India has emerged as the new epicenter of the second wave by mutants of SARS-CoV-2. After almost eighteen months of this outbreak, some COVID-19 dedicated therapeutics and vaccines are available, and a few are under trial, but the situation is still uncontrolled. Area covered This perspective article covers the repurposing of childhood vaccines like Bacille Calmette–Guerin (BCG), Measles, Mumps, Rubella (MMR), and Oral Polio Vaccine (OPV), which are live attenuated vaccines and have been shown the protective effect through ‘trained immunity and ‘crossreactivity.' Expert opinion This perspective article has suggested that combinatorial use of these childhood vaccines might exert a better protective effect along with the available COVID-19 therapeutic and vaccines which could be considered as a preventive option against SARS-CoV-2 infection as well as its subsequent waves.

In the present study, a range of serum biomarkers were quantified in suspected cases of adverse events following YF immunization (YEL-AEFI) to propose a reliable laboratorial algorithm to discriminate confirmed YEL-AEFI (“A1” class) from cases with other illnesses (“C” class). Our findings demonstrated that increased levels of CXCL8, CCL2, CXCL10, IL-1β, IL-6 and TNF-α were observed in YEL-AEFI (“A1” and “C” classes) as compared to primary vaccines without YEL-AEFI [PV(day 3–28)] and reference range (RR) controls. Notably, increased levels of CCL3, CCL4, CCL2, CCL5, IL-1β, IL-15, IL-1Ra and G-CSF were found in “A1” as compared to “C” class. Venn diagrams analysis allowed the pre-selection of biomarkers for further analysis of performance indices. Data demonstrated that CCL3, CCL5, IL-15 and IL-1Ra presented high global accuracy (AUC = 1.00) to discriminate “A1” from “C”. Decision tree was proposed with a reliable algorithm to discriminate YEL-AEFI cases according to cause-specific definitions with outstanding overall accuracy (91%). CCL3, CCL5, IL-15 and IL-1Ra appears as root attributes to identify “A1” followed by VEGF as branch nodes to discriminate Wild Type YFV infection (“C(WT-YFV)”) from cases with other illnesses (“C*”). Together, these results demonstrated the applicability of serum biomarker measurements as putative parameters towards the establishment of accurate laboratorial tools for complementary differential diagnosis of YEL-AEFI cases.

Examination of the vaccine strategies and technical platforms used for the COVID-19 pandemic in the context of those used for previous emerging and reemerging infectious diseases and pandemics may offer some mutually beneficial lessons. The unprecedented scale and rapidity of dissemination of recent emerging infectious diseases pose new challenges for vaccine developers, regulators, health authorities and political constituencies. Vaccine manufacturing and distribution are complex and challenging. While speed is essential, clinical development to emergency use authorization and licensure, pharmacovigilance of vaccine safety and surveillance of virus variants are also critical. Access to vaccines and vaccination needs to be prioritized in low- and middle-income countries. The combination of these factors will weigh heavily on the ultimate success of efforts to bring the current and any future emerging infectious disease pandemics to a close.

By preventing infectious diseases, vaccines contribute substantially to public health. Besides, they offer great opportunities to investigate human immune responses. This is particularly true for live-attenuated virus vaccines which cause resolving acute infections and induce robust immunity. The fact that one can precisely schedule the time-point of vaccination enables complete characterization of the immune response over time, short-term and over many years. The live-attenuated Yellow Fever virus vaccine strain YF-17D was developed in the 1930’s and gave rise to the 17D-204 and 17DD vaccine sub-strains, administered to over 600 million individuals worldwide. YF vaccination causes a systemic viral infection, which induces neutralizing antibodies that last for a lifetime. It also induces a strong T cell response resembling the ones of acute infections, in contrast to most other vaccines. In spite of its use since 1937, learning how YF vaccination stimulates such strong and persistent immune responses has gained substantial knowledge only in the last decades. Here we summarize the current state of knowledge on the immune response to YF vaccination, and discuss its contribution as a human model to address complex questions on optimal immune responses.

Highlights • This is the first study on the co-administration of typhoid conjugate vaccine (TCV) in West Africa. • Co-administration of TCV with routine vaccines in a typhoid-endemic country was successful. • TCV was safely co-administered at nine months with yellow fever and measles-rubella vaccines. • Single-dose TCV was immunogenic in 9-month-old children. • There was no safety signal related to TCV vaccination or co-administration., 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.

Experimental study of specific activity and harmlessness of simultaneous application of five vaccines (abdominal, Zonne dysentery, viral hepatitis A, meningococcal and live yellow fever vaccine) in complex immunoprophylaxis of dangerous infectious diseases was carried out. It has been found that the simultaneous administration of these vaccines is safe and has high immunogenicity and protective efficacy for each infection not inferior to, and in some cases superior to, vaccines administered separately. In particular, the immunogenicity of vaccines against typhoid fever and viral hepatitis A administered jointly was four times higher than with their separate administration, which may indicate the presence of a certain adjuvant effect on the part of other vaccines, as well as the absence of antagonism in their joint use. It was revealed that complex vaccinations do not negatively affect the functional state of cells involved in the initial stage of immunogenesis. The absence of a negative effect of complex vaccinations on the components of nonspecific resistance of the body was almost completely confirmed in the conditions of infection of immunized animals with influenza virus, that is, in modeling heterologous infection. In addition, immunization with a complex of vaccines does not lead to allergic animals, which is confirmed by the absence of any manifestations of allergic reactions or anaphylactic activity.

Background An effective yellow fever (YF) vaccine has been available since 1937. Nevertheless, questions regarding its use remain poorly understood, such as the ideal dose to confer immunity against the disease, the need for a booster dose, the optimal immunisation schedule for immunocompetent, immunosuppressed, and pediatric populations, among other issues. This work aims to demonstrate that computational tools can be used to simulate different scenarios regarding YF vaccination and the immune response of individuals to this vaccine, thus assisting the response of some of these open questions. Results This work presents the computational results obtained by a mathematical model of the human immune response to vaccination against YF. Five scenarios were simulated: primovaccination in adults and children, booster dose in adult individuals, vaccination of individuals with autoimmune diseases under immunomodulatory therapy, and the immune response to different vaccine doses. Where data were available, the model was able to quantitatively replicate the levels of antibodies obtained experimentally. In addition, for those scenarios where data were not available, it was possible to qualitatively reproduce the immune response behaviours described in the literature. Conclusions Our simulations show that the minimum dose to confer immunity against YF is half of the reference dose. The results also suggest that immunological immaturity in children limits the induction and persistence of long-lived plasma cells are related to the antibody decay observed experimentally. Finally, the decay observed in the antibody level after ten years suggests that a booster dose is necessary to keep immunity against YF.

Background - Yellow fever (YF) is a viral hemorrhagic fever that is transmitted by arthropods. It can occur with little symptomatic manifestations to the most fulminant forms. The most effective way to avoid YF is through vaccination. There is a lack of information about the immune response of the vaccine in childhood. Methods - We described children and adolescents with YF who had been previously immunized in Minas Gerais State from July 2017 to June 2018. Results - 527 cases of YF were observed representing an incidence of 7.6/100,000 inhabitants. Only 26 patients (4.9%) were ≤ 20 years and 501 (95.1%) were 20 years. Only 9 vaccinated patients were ≤ 20 years and 15 were 20 years. 34.6% (9/26) of YF patients ≤ 20 years were previously vaccinated and 3% (15/501) of those 20 years (p 0.001). The median age at vaccination was 1 year between those ≤ 20 years and 31 years between those 20 years (p = 0.002). Among 9 vaccinated children and adolescents ≤ 20 years, age ranged from 7 to 18 years, the most described symptoms were fever (88%), headache (77%), myalgia (77%), and abdominal pain (66%). All patients recovered from the disease and none died. Conclusion - Prior YF vaccination may be associated with mild forms of the disease in children and adolescents. YF vaccination in the first years of life may be associated with poor vaccine response and high infection rates in this group as it fail to seroconvert a significant proportion of infants.

Yellow Fever (YF) is an acute febrile illness caused by yellow fever virus (YFV), a mosquito-borne flavivirus transmitted to humans and non-human primates. In Brazil, YF is a public health threat and may cause recurrent epidemics, even with the availability of a vaccine. We evaluated the sero-status for YFV in 581 individuals living in a risk area for YF in Brazil. The area presents history of cases and is located in the southeast region of country where outbreaks of YF have been reported since 2016. Through, a PRNT assay, we found 25.8% of individuals lacking YF-neutralizing antibodies. Furthermore, neutralizing antibodies were not detected in 10 individuals with proven vaccination. Our findings reinforce the importance of surveillance systems and the need of an urgent intensification of immunization programs in regions with YFV circulation. Monitoring susceptible individuals that could act as potential disseminators for YFV in risk areas should also be considered.

Insufficient vaccine doses and the lack of therapeutic agents for yellow fever put global health at risk, should this virus emerge from sub-Saharan Africa and South America.In phase 1a of this clinical trial, we assessed the safety, side-effect profile, and pharmacokinetics of TY014, a fully human IgG1 anti-yellow fever virus monoclonal antibody. In a double-blind, phase 1b clinical trial, we assessed the efficacy of TY014, as compared with placebo, in abrogating viremia related to the administration of live yellow fever vaccine (YF17D-204; Stamaril). The primary safety outcomes were adverse events reported 1 hour after the infusion and throughout the trial. The primary efficacy outcome was the dose of TY014 at which 100% of the participants tested negative for viremia within 48 hours after infusion.A total of 27 healthy participants were enrolled in phase 1a, and 10 participants in phase 1b. During phase 1a, TY014 dose escalation to a maximum of 20 mg per kilogram of body weight occurred in 22 participants. During phases 1a and 1b, adverse events within 1 hour after infusion occurred in 1 of 27 participants who received TY014 and in none of the 10 participants who received placebo. At least one adverse event occurred during the trial in 22 participants who received TY014 and in 8 who received placebo. The mean half-life of TY014 was approximately 12.8 days. At 48 hours after the infusion, none of the 5 participants who received the starting dose of TY014 of 2 mg per kilogram had detectable YF17D-204 viremia; these participants remained aviremic throughout the trial. Viremia was observed at 48 hours after the infusion in 2 of 5 participants who received placebo and at 72 hours in 2 more placebo recipients. Symptoms associated with yellow fever vaccine were less frequent in the TY014 group than in the placebo group.This phase 1 trial of TY014 did not identify worrisome safety signals and suggested potential clinical benefit, which requires further assessment in a phase 2 trial. (Funded by Tysana; ClinicalTrials.gov number, NCT03776786.).

Background To optimize vaccine implementation visits for young children, it could be efficient to administer the first RTS,S/AS01 malaria vaccine dose during the Expanded Programme on Immunization (EPI) visit at 6 months of age together with Vitamin A supplementation and the third RTS,S/AS01 dose on the same day as yellow fever (YF), measles and rubella vaccines at 9 months of age. We evaluated the safety and immunogenicity of RTS,S/AS01 when co-administered with YF and combined measles-rubella (MR) vaccines. Methods In this phase 3b, open-label, controlled study (NCT02699099), 709 Ghanaian children were randomized (1:1:1) to receive RTS,S/AS01 at 6, 7.5 and 9 months of age, and YF and MR vaccines at 9 or 10.5 months of age (RTS,S coad and RTS,S alone groups, respectively). The third group received YF and MR vaccines at 9 months of age and will receive RTS,S/AS01 at 10.5, 11.5 and 12.5 months of age (Control group). All children received Vitamin A at 6 months of age. Non-inferiority of immune responses to the vaccine antigens was evaluated 1 month following co-administration versus RTS,S/AS01 or EPI vaccines (YF and MR vaccines) alone using pre-defined non-inferiority criteria. Safety was assessed until Study month 4.5. Results Non-inferiority of antibody responses to the anti-circumsporozoite and anti-hepatitis B virus surface antigens when RTS,S/AS01 was co-administered with YF and MR vaccines versus RTS,S/AS01 alone was demonstrated. Non-inferiority of antibody responses to the measles, rubella, and YF antigens when RTS,S/AS01 was co-administered with YF and MR vaccines versus YF and MR vaccines alone was demonstrated. The safety profile of all vaccines was clinically acceptable in all groups. Conclusions RTS,S/AS01 can be co-administered with Vitamin A at 6 months and with YF and MR vaccines at 9 months of age during EPI visits, without immune response impairment to any vaccine antigen or negative safety effect.

Yellow fever (YF) is an acute viral hemorrhagic disease caused by the YF virus (arbovirus) which continues to cause severe morbidity and mortality in Africa. A case of YF was confirmed in Nigeria on the 12th of September 2017, 21 years after the last confirmed case. The patient belongs to a nomadic population with a history of low YF vaccination uptake, in the Ifelodun Local Government Area (LGA) of Kwara State, Nigeria. An active case search in Ifelodun and its five contiguous LGAs led to the listing of 55 additional suspect cases of YF within the period of the outbreak investigation between September 18 to October 6, 2017. The median age of cases was 15 years, and 54.4% were males. Of these, blood samples were collected from 30 cases; nine tested positive in laboratories in Nigeria and six were confirmed positive for YF by the WHO reference laboratory in the region; Institut Pasteur, Dakar. A rapid YF vaccination coverage assessment was carried out, resulting in a coverage of 46% in the LGAs, with 25% of cases able to produce their vaccination cards. All stages of the yellow fever vector, Aedes mosquito were identified in the area, with high larval indices (House and Breteau) observed. In response to the outbreak, YF surveillance was intensified across all States in Nigeria, as well as reactive vaccination and social mobilisation campaigns carried out in the affected LGAs in Kwara State. A state-wide YF preventive campaign was also initiated.

Responses to vaccination and to diseases vary widely across individuals, which may be partly due to baseline immune variations. Identifying such baseline predictors of immune responses and their biological basis is of broad interest, given their potential importance for cancer immunotherapy, disease outcomes, vaccination and infection responses. Here we uncover baseline blood transcriptional signatures predictive of antibody responses to both influenza and yellow fever vaccinations in healthy subjects. These same signatures evaluated at clinical quiescence are correlated with disease activity in patients with systemic lupus erythematosus with plasmablast-associated flares. CITE-seq profiling of 82 surface proteins and transcriptomes of 53,201 single cells from healthy high and low influenza vaccination responders revealed that our signatures reflect the extent of activation in a plasmacytoid dendritic cell–type I IFN–T/B lymphocyte network. Our findings raise the prospect that modulating such immune baseline states may improve vaccine responsiveness and mitigate undesirable autoimmune disease activity. Simultaneous single-cell protein and transcriptome analysis identifies a baseline immune circuit associated with antibody responses to vaccination in healthy individuals and the severity of disease flares in patients with a subtype of systemic lupus erythematosus.

To summarize the lot release of live attenuated yellow fever vaccine in China during 2011-2018 and evaluate the total quality as well as problem in quality control of the vaccine. By reviewing the data and laboratory test，34 batches of live attenuated yellow fever vaccine were determined for virus titer according to the standard for license, of which 52 batches were determined for ovalbumin residue by ELISA, and 14 batches for moisture. The determination results were subjected to statistical and quality trend analyses, and compared with those by the manufacturers，based on which the general status of vaccine quality was reviewed. All the determination results of virus titer, ovalbumin residue and moisture met the requirements in Chinese Pharmacopoeia, and there is no difference in those by the manufacturers and those by the National Institutes for Food and Drug Control . The quality of live attenuated yellow fever vaccine was stable, which met the requirements in Chinese Pharmacopoeia. The implementation of lot release, batch inspection and trend analysis may effectively regulate and supervise the vaccine production．

Background In 2013, the World Health Organization (WHO) revised their position on yellow fever vaccination, in which revaccination every 10 years was no longer required, and that a single-dose provided life-long protection. However, research data on the immunogenicity of YF vaccine in people aged 60 years and over are scarce. Indeed, immunosenescence may result in lower virus neutralizing antibody titers after primary vaccination and a more rapid waning immunity. Therefore, we tested the hypothesis that older travelers, vaccinated at 60 years or older are more likely to become seronegative in comparison to young adults 10 years after primary YF vaccination. Methods This is a 10-year follow-up study of an earlier prospective controlled cohort study. In the original trial, the neutralizing antibody response was measured in older travelers (aged 60–81 years, N = 28) and young adults (aged 18–28 years, N = 30) up to 28 days after a primary yellow fever vaccination. Ten years later, we collected serum samples of 22/28 (78%) elderly (71–85 years) and 14/30 (47%) controls (29–40 years), and determined their neutralizing antibody titers by plaque reduction neutralization test (PRNT80). Seropositivity was defined as plaque formation reduction of 80% at a serum dilution of 10 or more (PRNT80 ≥ 10). Results All participants (36/36) were still seropositive 10 years after primary vaccination. The geometric mean concentrations were not statistically different between the older and younger participants (6.7 IU/mL vs. 8.6 IU/mL, P = 0.5). Conclusions All older travelers were seropositive, 10 years after a primary YF vaccination at the age of ≥60 years. These data suggest that in older travelers a single vaccination is sufficient to convey long-lasting immunity for at least 10 years, and is in support the position of the WHO on a single-dose yellow fever vaccination.

The pretravel management of the international pediatric traveler is based on provision of preventive education, chemoprophylaxis against malaria and traveler's diarrhea, as well as travel vaccinations. Immunization requirements are determined based on the traveler's pretravel immunization status, age, medical history, and destination. Immunization needs also vary depending on the exposures during the trip. Potential exposure to water, insects, or animals as well as duration of travel will help tailor risk avoidance education and travel immunizations. This review provides clinicians an overview of vaccines recommended for children traveling internationally.

Yellow fever is an emerging infectious disease, with epidemics occurring in Africa and South America, and poses great concern due to high lethality rates of up to 60% in severe cases, despite the availability of an efficacious vaccine. In this paper, we sought to review the epidemiology, clinical manifestations, diagnosis, prevention strategies, and treatment in overall and in the transplant population. Yellow fever control relies mainly on adequate vaccine coverage, and as the yellow fever vaccine is composed of live, attenuated virus, it is contraindicated in the immunosuppressed individuals, including solid organ transplant and hematopoietic stem cell transplant recipients. Therefore, these patients should be preferably vaccinated in the pre-transplant period. There are few case series where vaccine is given to immunocompromised patients that showed a low incidence of adverse effects, although the number of patients in these reports is small. Donors who live in or with recent travel to yellow fever endemic or epidemic areas should be evaluated as to their suitability for donation. There is no specific therapy for infection and supportive treatment in intensive care units is required in severe cases. Recently, liver transplantation has been performed in several severe yellow fever cases, and although it was lifesaving in some, overall, there were high post-transplant mortality rates. Yellow fever is still responsible for devastating epidemics, and some particularities pertaining to the transplant population are discussed. Prevention strategies including vaccination in the pre-transplant period and recommendations for donors living or with recent travel to yellow fever high-risk areas are discussed, as well as recent attempts of treatment with liver transplantation in severe cases.

Background:Pneumococcal conjugate vaccines (PCV) effectively prevent pneumococcal disease but the global impact of pneumococcal vaccination is hampered by its cost. The evaluation of reduced dose schedules of PCV includes measurement of effects on immunogenicity and carriage acquisition compared to standard schedules. The relevance and feasibility of trials of reduced dose schedules is greatest in middle- and low-income countries, such as The Gambia, where the introduction of PCV resulted in good disease control but where transmission of vaccine-type pneumococci persists. We designed a large cluster-randomised field trial of an alternative reduced dose schedule of PCV compared to the standard schedule, the PVS trial. We will also conduct a sub-study to evaluate the individual-level effect of the two schedules on carriage acquisition, immunogenicity, and co-administration of PCV with yellow fever vaccine, the PVS-AcqImm trial.Methods:PVS-AcqImm is prospective, cluster-randomised trial of one dose of PCV scheduled at age 6 weeks with a booster dose at age 9 months (i.e. alternative ‘1+1’ schedule) compared to three primary doses scheduled at 6, 10, and 14 weeks weeks of age (i.e. stardard ‘3+0’ schedule). Sub-groups within the alternative schedule group will receive yellow fever vaccine separately or co-administered with PCV at 9 months of age. The primary endpoints are: a) rate of nasopharyngeal vaccine-type pneumococcal acquisition from 9-14 months of age, b) geometric mean concentration of vaccine-type pneumococcal IgG at 18 months of age, and c) proportions with yellow fever neutralizing antibody titre ≥8 four weeks after administration of yellow fever vaccine. Participants and field staff will not be masked to group allocation while the measurement of laboratory endpoints will be masked. Approximately equal numbers of participants will be resident in each of 28 geographic clusters (14 clusters in alternative and standard schedule groups); 784 enrolled for acquisition measurements and 336 for immunogenicity measurements. Discussion:Analysis will account for potential non-independence of measurements by cluster and so interpretation of effects will be at the individual level (i.e. a population of individuals). PVS-AcqImm will evaluate whether acquisition of vaccine-type pneumococci is reduced by the alternative compared to standard schedule, which is required if the alternative schedule is to be effective. Likewise, evidence of superior immune response at 18 months of age and safety of PCV co-administration with yellow fever vaccine will support decision-making regarding the use of the alternative 1+1 schedule. Acquisition and immunogenicity outcomes will be essential for interpretation of the results of the large field trial comparing the two schedules.Trial registration: International Standard Randomised Controlled Trial Number – 72821613.

Invasive aspergillosis (IA) usually occurs in immunocompromised hosts, but in the last decade IA has emerged in critically ill non-neutropenic patients, as those with severe Influenza and Chronic Obstructive Pulmonary Disease (COPD). We report an unusual fatal case of disseminated IA in a non-immunocompromised patient following yellow fever vaccine-associated viscerotropic disease.

Summary Background Childhood immunisation services have been disrupted by the COVID-19 pandemic. WHO recommends considering outbreak risk using epidemiological criteria when deciding whether to conduct preventive vaccination campaigns during the pandemic. Methods We used 2-3 models per infection to estimate the health impact of 50% reduced routine vaccination coverage in 2020 and delay of campaign vaccination from 2020 to 2021 for measles vaccination in Bangladesh, Chad, Ethiopia, Kenya, Nigeria, and South Sudan, for meningococcal A vaccination in Burkina Faso, Chad, Niger, and Nigeria, and for yellow fever vaccination in the Democratic Republic of Congo, Ghana, and Nigeria. Our counterfactual comparative scenario was sustaining immunisation services at coverage projections made prior to COVID-19 (i.e. without any disruption). Findings Reduced routine vaccination coverage in 2020 without catch-up vaccination may lead to an increase in measles and yellow fever disease burden in the modelled countries. Delaying planned campaigns in Ethiopia and Nigeria by a year may significantly increased the risk of measles outbreaks (both countries did complete their SIAS planned for 2020). For yellow fever vaccination, delay in campaigns leads to a potential disease burden rise of >1 death per 100,000 people until the campaigns are implemented. For meningococcal A vaccination, short term disruptions in 2020 are unlikely to have a significant impact due to the persistence of direct and indirect benefits from past introductory campaigns of the 1 to 29-year-old population, bolstered by inclusion of the vaccine into the routine immunisation schedule accompanied by further catch-up campaigns. Interpretation The impact of COVID-19-related disruption to vaccination programs varies between infections and countries. Planning and implementation of campaigns should consider country and infection-specific epidemiological factors and local immunity gaps worsened by the COVID-19 pandemic when prioritising vaccines and strategies for catch-up vaccination. Funding Bill & Melinda Gates Foundation and Gavi, the Vaccine Alliance Research in context Evidence before the study We searched PubMed for (COVID-19 OR coronavirus OR SARS-CoV-2) AND (child health intervention OR vaccin* or immuni*) AND (disruption OR suspension OR reduction) AND (indirect effect OR health impact) on January 14, 2021, with no language restrictions. We found 178 articles of which 13 articles were relevant. Six articles reported some empirical data on immunization disruption in Bangladesh, Japan, Kenya, Nigeria, Pakistan, Saudi Arabia, South Africa, Spain and Italy, and a survey study focussed on immunization disruption in low and middle-income countries. One article proposed using the WHO health systems framework to assess the effects of COVID-19 on immunisation programmes in South Africa, another study on leveraging systems thinking and implementation science to improve immunization system performance in Africa, and two studies were review articles. One modelling study focused on the indirect effects, including reduction in routine immunisation services, of the COVID-19 pandemic on maternal and child mortality in low-income and middle-income countries. Another modelling study focused on a benefit-risk analysis of routine childhood immunisation during the COVID-19 pandemic in Africa. We also found one other study in the grey literature that analysed the impact on SARS-CoV-2 infections as a result of fixed-post and door-to-door vaccination campaigns targeted at children under five years of age in an Ethiopia-like setting. Added value of this study We estimated the increase in cases and deaths caused by the disruption to immunisation services leading to outbreaks for measles, meningococcal A and yellow fever in 10 countries. The reduction in routine immunisation coverage among under-immunised cohorts of children has enhanced the risk of outbreaks which cannot be averted without catch-up vaccination. This can lead to an increase of 9.89% (0.91 additional deaths per 100,000 individuals, or 48,000 in total) across the three diseases from 2020 to 2030 in the countries considered. Results vary by infection and country, but generally most excess deaths are due to measles. Postponing campaign immunisation may not have a detrimental short-term health impact if campaign immunisation is implemented ahead of future outbreaks caused by these immunity gaps. Implications of the available evidence The COVID-19 pandemic has caused significant disruptions to routine services and vaccination campaigns and resulted in immunity gaps with potential to cause outbreaks in the affected populations. The short-term and long-term health impact differ between measles, meningococcal A and yellow fever vaccination and by countries based on the local epidemiological situation. Thereby, catch-up vaccination should be planned by considering the heterogeneity in population susceptibility across different countries to measles, meningococcal A and yellow fever outbreaks and implemented in time to prevent these outbreaks. The study findings can inform risk-benefit trade-off discussions around the timing of campaigns.

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.

Yellow fever (YF) is a vaccine-preventable disease, but live attenuated YF vaccine (YFV) is contraindicated in immunosuppressed patients due to the risk of life-threatening YFV-associated side effects. This study aimed to evaluate 1. the knowledge of renal transplant recipients (RTRs) about the contraindication and risks of YFV; 2. the prevalence of inadvertent vaccination of RTRs against YF; and 3. the outcome of these patients. A cross-sectional telephone contact study was conducted with 200 RTRs selected from the outpatient clinic of our transplantation unit. There were 116 successful telephone contacts (58%). A total of 11 vaccinated patients were identified: 5 received YFV in the pretransplant period and 6 in the post-transplant period. All patients received the full dose of the vaccine. Among those vaccinated after transplant, only 1 reported a mild adverse event (nausea) after receiving the vaccine. All vaccinated patients who were post-transplant did not know about vaccine contraindications as a result of their clinical condition. Among the unvaccinated patients, this rate was 12.4%. YFV is the main tool for disease prevention and control as there is no specific antiviral treatment for YF. Our results confirm the evidence that transplant recipients tolerate YFV well. However, data are not strong enough to recommend this vaccine in transplant recipients. Counseling RTRs on the contraindications of YFV is important to prevent inadvertent use of this vaccine in this population.

As research efforts have advanced to understand the pathophysiology of viral hemorrhagic fevers (VHF) and other epidemic viral infections and develop medical countermeasures such as vaccines, pregnant women have remained an underexamined subgroup. To better understand the implications of future outbreaks of VHF for pregnant women amidst an evolving vaccine landscape, we examine three pathogens—yellow fever, Ebola, and Lassa fever—each with different levels of evidence and understanding of disease in pregnancy and at varying stages of vaccine development. There are very limited data available on yellow fever disease in pregnancy and the current live-attenuated 17D yellow fever vaccine is recommended for pregnant women at high risk of exposure. Evidence on Ebola virus disease in pregnancy shows very high case fatality rates (CFRs) among pregnant women and their infants, with mixed evidence on whether mortality is higher in pregnant women than non-pregnant adults. The replication-competent rVSV-ZEBOV vaccine is currently being offered to at-risk pregnant women in the Democratic Republic of the Congo after a revision to an earlier protocol that excluded them. For Lassa fever, there is evidence that CFR is higher in pregnant individuals than non-pregnant adults, especially later in gestation, with high rates of fetal or perinatal loss associated with infection. There are currently no Lassa fever vaccine candidates that have been tested in humans. More evidence is needed to fully understand the implications of infection in pregnancy, but the existing data underscore the serious maternal and fetal health risks associated with each viral infection. It will also be critical to generate evidence on the safety profile of vaccine candidates as they advance through the pipeline to ensure timely and appropriate access for pregnant women at risk of infection. It is important that pregnant women be considered in the design and clinical trial phases of future vaccines.

Purpose: To report the manifestation of Vogt–Koyanagi–Harada-like disease (VKH) following yellow fever vaccination.Methods: Case report.Results: A 34-year-old immunocompetent male had tinnitus, hea...

Background The once-in-a-lifetime recommendation for vaccination against yellow fever virus (YFV) has been controversial, leading to increased scrutiny of the durability of immunity after 17D vaccination. Methods This is a cross-sectional analysis of 17D vaccinees living in nonendemic Portland, Oregon. Neutralization assays were used to determine YFV immunity. The relationships between 17D immunity and vaccination history, demographics, and travel were evaluated using nominal logistic regression. Results Seventy-one of 92 (77.2%) subjects were YFV seropositive (90 percent plaque reduction neutralization test ≥1:10) at all timepoints, and 24 of 38 (63.8%) were YFV seropositive at ≥10 years after single-dose vaccination. No relationship was found between YFV immunity and time in endemic countries, other flavivirus immunity, or demographics. Subjects were most likely to become seronegative between 3 and 12 years postvaccination (logistic regression, odds ratio [OR] = 1.75; 95% confidence interval [CI], 1.12–2.73). A comparison of our results and 4 previous studies of YFV nonendemic vaccinees found that overall, 79% (95% CI, 70%–86%) of vaccinees are likely to be seropositive ≥10 years postvaccination. Conclusions These results suggest that 1 in 5 17D vaccinees will lack neutralizing antibodies at ~10 years postvaccination, and a booster vaccination should be considered for nonendemic vaccinees before travel to regions where there is a high risk of YFV transmission.

BACKGROUND: In 2016, the response to a yellow fever outbreak in Angola and the Democratic Republic of Congo led to a global shortage of yellow fever vaccine. As a result, a fractional dose of the 17DD yellow fever vaccine (containing one fifth [0.1 ml] of the standard dose) was offered to 7.6 million children 2 years of age or older and nonpregnant adults in a preemptive campaign in Kinshasa. The goal of this study was to assess the immune response to the fractional dose in a large-scale campaign. METHODS: We recruited participants in four age strata at six vaccination sites. We assessed neutralizing antibody titers against yellow fever virus in blood samples obtained before vaccination and at 1 month and 1 year after vaccination, using a plaque reduction neutralization test with a 50% cutoff (PRNT(50)). Participants with a PRNT(50) titer of 10 or higher were considered to be seropositive. Those with a baseline titer of less than 10 who became seropositive at follow-up were classified as having undergone seroconversion. Participants who were seropositive at baseline and who had an increase in the titer by a factor of 4 or more at follow-up were classified as having an immune response. RESULTS: Among 716 participants who completed the 1-month follow-up, 705 (98%; 95% confidence interval [CI], 97 to 99) were seropositive after vaccination. Among 493 participants who were seronegative at baseline, 482 (98%; 95% CI, 96 to 99) underwent seroconversion. Among 223 participants who were seropositive at baseline, 148 (66%; 95% CI, 60 to 72) had an immune response. Lower baseline titers were associated with a higher probability of having an immune response (P

We describe two unrelated patients with inherited IFNAR1 deficiency who suffered from life-threatening infections following measles or yellow fever virus vaccination and were otherwise healthy., Vaccination against measles, mumps, and rubella (MMR) and yellow fever (YF) with live attenuated viruses can rarely cause life-threatening disease. Severe illness by MMR vaccines can be caused by inborn errors of type I and/or III interferon (IFN) immunity (mutations in IFNAR2, STAT1, or STAT2). Adverse reactions to the YF vaccine have remained unexplained. We report two otherwise healthy patients, a 9-yr-old boy in Iran with severe measles vaccine disease at 1 yr and a 14-yr-old girl in Brazil with viscerotropic disease caused by the YF vaccine at 12 yr. The Iranian patient is homozygous and the Brazilian patient compound heterozygous for loss-of-function IFNAR1 variations. Patient-derived fibroblasts are susceptible to viruses, including the YF and measles virus vaccine strains, in the absence or presence of exogenous type I IFN. The patients’ fibroblast phenotypes are rescued with WT IFNAR1. Autosomal recessive, complete IFNAR1 deficiency can result in life-threatening complications of vaccination with live attenuated measles and YF viruses in previously healthy individuals.

Introduction The strategy to Eliminate Yellow Fever Epidemics (EYE) is a global initiative that includes all countries with risk of yellow fever (YF) virus transmission. Of these, 40 countries (27 in Africa and 13 in the Americas) are considered high-risk and targeted for interventions to increase coverage of YF vaccine. Even though the World Health Organization (WHO) recommends that YF vaccine be given concurrently with the first dose of measles-containing vaccine (MCV1) in YF-endemic settings, estimated coverage for MCV1 and YF vaccine have varied widely. The objective of this study was to review global data sources to assess discrepancies in YF vaccine and MCV1 coverage and identify plausible reasons for these discrepancies. Methods We conducted a desk review of data from 34 countries (22 in Africa, 12 in Latin America), from 2006 to 2016, with national introduction of YF vaccine and listed as high-risk by the EYE strategy. Data reviewed included procured and administered doses, immunization schedules, routine coverage estimates and reported vaccine stock-outs. In the 30 countries included in the comparitive analysis, differences greater than 3 percentage points between YF vaccine and MCV1 coverage were considered meaningful. Results In America, there were meaningful differences (7–45%) in coverage of the two vaccines in 6 (67%) of the 9 countries. In Africa, there were meaningful differences (4–27%) in coverage of the two vaccines in 9 (43%) of the 21 countries. Nine countries (26%) reported MVC1 stock-outs while sixteen countries (47%) reported YF vaccine stock-outs for three or more years during 2006–2016. Conclusion In countries reporting significant differences in coverage of the two vaccines, differences may be driven by different target populations and vaccine availability. However, these were not sufficient to completely explain observed differences. Further follow-up is needed to identify possible reasons for differences in coverage rates in several countries where these could not fully be explained.

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.

The recent Typhoid Fever Surveillance in Africa Program demonstrated an overall adjusted incidence of typhoid fever 2–3 times higher than previous estimates in Africa. Recently, a single-dose typhoid conjugate vaccine that allows infants as young as 6 months old to be vaccinated was prequalified by the World Health Organization (WHO). This Vi-based conjugate vaccine demonstrated robust immunogenicity after 1 dose in infants and children 6 through 23 months of age in India with no safety signal, and is currently being tested for the first time on the African continent in Malawi. The WHO Strategic Advisory Group of Experts recommends studies to evaluate co-administering Vi-typhoid conjugate vaccine (Vi-TCV) with routine childhood vaccines in typhoid-endemic countries. The Burkina Faso immunization schedule includes yellow fever vaccine (YFV) at 9 months and meningococcal A conjugate vaccine (MCV-A) at 15 months, in addition to measles-rubella vaccine at both 9 and 15 months. Co-administration testing of Vi-TCV with these routine vaccinations will provide the data needed to support large-scale uptake of Vi-TCV in sub-Saharan Africa. A randomized, controlled, Phase II trial of Vi-TCV co-administration with the vaccinations routinely given at 9 and 15 months of age is planned in Burkina Faso. The overall aim is to assess the safety and immunogenicity of Vi-TCV when co-administered with YFV at 9 months of age and with MCV-A at 15 months of age. A total of 250 participants (100 infants aged 9–11 months and 150 children aged 15–23 months) will be enrolled. Clinical Trials Registration. NCT03614533.

Summary Objectives Unemployment in Greece has been increasing as a result of the financial crisis. The aim of this study was to assess the changing trends of business travelers and their pretravel preparation. Study design Prospective, questionnaire-based study. Methods The study was conducted between 2008 and 2016 at all Regional Public Health Departments. All travelers seeking pretravel advice during the study period were invited to participate. Results A total of 12,379 travelers completed the questionnaire, 58% of whom were business travelers. Between 2008 and 2016, the proportion of business travelers increased from 33% to 80.7% and those travelling for recreational purposes decreased from 47.9% to 15.5%. Business travelers sought pretravel advice at a mean of 18.5 days before departure; 89.1% were men with a mean age of 34.4 years. The Middle East was the most common destination (47.8%) followed by Sub-Saharan Africa (28.3%). Most business travelers stayed in urban areas (77.6%) and for ≥ 1 month (68.6%). Yellow fever vaccine was administered to 75% of business travelers. A total of 76.2%, 26.9%, 15.5%, and 13.9% of those visiting Sub-Saharan Africa received yellow fever, typhoid fever, hepatitis A, and meningococcal vaccines, respectively. Malaria prophylaxis vaccine was administered to 26.8% of business travelers; including 46.5% of those traveling to Sub-Saharan Africa and 53.5% to those traveling to the Indian subcontinent. Conclusions There is an increasing trend for business travel from Greece, especially to developing countries. Improving the knowledge of travel health consultants about the risks of business travel and the pretravel preparation of business travelers is crucial.

Vaccines are formulations that equip the human immune system to fight against a pathogen. All the vaccines approved for use are safe. On vaccination, the body produces enough clonal B and T cells to resist infection. Vaccines are the most cost-effective defense against infectious diseases. In India, there are at least 19 manufactures of vaccines. In addition, there are also a large number of companies that import specific vaccine formulations and sell these in India. These include two multinational companies that have also established repacking facilities. India has a well-established Universal Immunization Program (UIP) that targets vaccination of 30 million pregnant women and 27 million newborns annually. Indian vaccines are available at affordable prices to the private consumers but are supplied free of cost to the Indian beneficiaries through the UIP. Several kinds of vaccines technology are being researched all over the world. India has concentrated on the production and supply of conventional vaccines at cost-effective prices. India is also engaged in some level of research at manufacturing companies as well as at the institutional level. Effective vaccination of pregnant women and children would translate into a generally more healthy and productive society globally. India is poised to contribute in such an endeavor.

Copyright © Ordem dos Médicos 2018, Introduction: Yellow fever is a vector-borne disease in sub-Saharan Africa and tropical South America regions which is preventable by an effective and safe vaccine. In some cases, it may cause serious adverse effects and should therefore be prescribed only to individuals at risk of exposure to the yellow fever virus or those traveling to countries requiring proof of vaccination. The aim of this study was to analyze the prescriptions of yellow fever vaccine, based on travel destination and type of referring consultation, according to the international recommendations of the World Health Organization. Material and Methods: The database of the International Vaccination Centre of the International Vaccination Centre of the LouresOdivelas Health Centre Group was used to analyze data concerning the year of 2016. Travelers who were prescribed and administered the yellow fever vaccine were grouped based on travel destination and type of referring consultation (travelers’ medical consultations or non-specialist consultations). Results: A total of 517 yellow fever vaccines were administered, with the highest proportion in female (53%) and in individuals aged 40 - 49 years (20.7%). One hundred and thirteen (22.6%) of the 499 individuals with known-destinations were travelling to nonendemic/non-epidemic countries and a greater proportion of those were prescribed in non-specialist consultations (27.3%) than in travel medicine consultations (8.8%). Discussion/Conclusion: The highest percentage of yellow fever vaccines that were administered to individuals travelling to nonendemic/non-epidemic countries were prescribed in non-specialist consultations., Introdução: A febre amarela é uma doença de transmissão vetorial que ocorre na África Subsaariana e na América do Sul tropical, e é evitável por uma vacina eficaz e segura. Nalguns casos pode causar efeitos adversos graves, devendo ser prescrita apenas a indivíduos em risco de exposição ao vírus ou que viajem para países que exigem prova de vacinação. O objetivo deste estudo foi analisar a prescrição da vacina contra a febre amarela, de acordo com o destino da viagem e o tipo de consulta de referenciação, segundo as recomendações internacionais da Organização Mundial de Saúde. Material e Métodos: Foi analisada a base de dados existente no Centro de Vacinação Internacional do Agrupamento de Centros de Saúde Loures-Odivelas, referente a 2016. Foram estudados os registos dos viajantes a quem foi prescrita e administrada a vacina contra a febre amarela, de acordo com o destino da viagem e o tipo de consulta de referenciação (consulta de medicina do viajante ou consulta não especializada). Resultados: Foram administradas no total 517 vacinas contra a febre amarela, em maior proporção em indivíduos do sexo feminino (53%) e em indivíduos dos 40 aos 49 anos de idade (20,7%). Dos 499 indivíduos que tinham destino conhecido, 113 (22,6%) tinham como destino países não endémicos/não epidémicos, com uma maior proporção de prescrições em contexto de consultas não especializadas (27,3%) do que em consultas de medicina do viajante (8,8%). Discussão/Conclusão: A maior percentagem de vacinas contra a febre amarela administradas a indivíduos que tiveram como destino países não endémicos/não epidémicos foram prescritas numa consulta não especializada.

Despite the existence of a highly efficient yellow fever vaccine, yellow fever reemergence throughout Africa and the Americas has put 900 million people in 47 countries at risk of contracting the disease. Although the vaccine has been key to controlling yellow fever epidemics, its live-attenuated nature comes with a range of contraindications that prompts advising against its administration to pregnant and lactating women, immunocompromised individuals, and those with hypersensitivity to chicken egg proteins. Additionally, large outbreaks have highlighted problems with insufficient vaccine supply, whereby manufacturers rely on slow traditional manufacturing processes that prevent them from ramping up production. These limitations have contributed to an inadequate control of yellow fever and have favored the pursuit of novel yellow fever vaccine candidates that aim to circumvent the licensed vaccine's restrictions. Here, we review the live-attenuated vaccine's limitations and explore the epitome of a yellow fever vaccine, whilst scrutinizing next-generation vaccine candidates.

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.

Background: Yellow fever vaccine (YFV) is not advised for multiple sclerosis (MS) patients because of the potential risk of post-vaccine relapses. Objective: To assess the risk of relapsing-remitting multiple sclerosis (RR-MS) worsening after YFV. Methods: Non-interventional observational retrospective, exposed/non-exposed cohort study nested in the French national cohort including MS. Results: 128 RR-MS were included. The 1-year annualized relapse rate (ARR) following YFV did not differ between exposed: 0.219 (0.420) and non-exposed subjects: 0.208 (0.521) ( p = 0.92). Time to first relapse was not different between groups (adjusted hazard ratio (HR) = 1.33; 95% confidence interval (CI) = 0.53–3.30, p = 0.54). Conclusion: These results suggest that YFV does not worsen the course of RR-MS.

Background & Aims Current standard-of-care suppresses HBV replication, but does not lead to a functional cure. Treatment aiming to cure chronic hepatitis B (CHB) is believed to require the induction of strong cellular immune responses, such as by therapeutic vaccination. Methods We designed a therapeutic HBV vaccine candidate (YF17D/HBc-C) using yellow fever vaccine YF17D as a live-attenuated vector to express HBV core antigen (HBc). Its ability to induce potent cellular immune responses was assessed in a mouse model that supports flavivirus replication. Results Following a HBc protein prime, a booster of YF17D/HBc-C was found to induce vigorous cytotoxic T cell responses. In a direct head-to-head comparison, these HBc-specific responses exceeded those elicited by adenovirus-vectored HBc. Target-specific T cells were not only more abundant, but also showed a higher degree of polyfunctionality, with HBc-specific CD8+ T cells producing interferon γ and tumour necrosis factor α in addition to granzyme B. This immune phenotype translated into a superior cytotoxic effector activity toward HBc-positive cells in YF17D/HBc-C vaccinated animals in vivo. Conclusions The results presented here show the potential of YF17D/HBc-C as a vaccine candidate to treat CHB, and warrant follow-up studies in preclinical animal models of HBV persistence in which other candidate vaccines have been unable to achieve a sustained virologic response. Lay summary Resolution of CHB requires the induction of strong cellular immune responses. We used the yellow fever vaccine as a vector for HBV antigens and show that it is capable of inducing high levels of HBV-specific T cells that produce multiple cytokines simultaneously and are cytotoxic in vivo., Graphical abstract, Highlights • Resolution of CHB requires the induction of vigorous cellular immune responses. • Yellow fever vaccine (YF17D) is safe, and can serve as potent viral vector for foreign antigens. • HBc is a relevant therapeutic target in CHB. • YF17D-vectored HBc might elicit more potent and particularly polyfunctional T cell responses compared with other vaccine modalities.

On the Shoulders of Giants The FDA recently authorized two mRNA vaccines for the prevention of Covid-19. Clearance of this hurdle represents the most recent in a series of advances in the realm of ...

Background Yellow Fever (YF) immunization required a single dose vaccine with boosters every 10 years. After International Health Regulation (IHR) amendment annex 7 (July 2016), it was accepted that a single dose confers lifelong immunity. Since pre-travel advice is as important as vaccination when traveling, it is essential to clarify why travelers come to a travel health consultation, with the possibility of IHR amendment having a negative impact on travelers’ health. This study aims to describe travelers’ reasons to come to a pre-travel consultation in Lisbon and if they would return if they wouldn’t need the YF vaccine booster. Methods An observational cross-sectional study was conducted during 5 months in the waiting room of Instituto de Higiene e Medicina Tropical travel clinic in Lisbon, Portugal. Travelers were asked about sociodemographic characteristics, destination country, travel duration and reasons to travel in an anonymous self-administered questionnaire. Results A total of 1043 travelers agreed to participate in the study. Although 61.0% (627/1028) did not come to the clinic to get the YF vaccine, from those who did, 36.7% (133/362) would not come and 12.9% (47/362) didn’t knew if they would come if the vaccine would not be necessary. Conclusion The IHR amendment may have a negative impact on travel clinic attendance and on travelers´ health.

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 is a viral hemorrhagic disease, and vaccination is the most effective way to minimize the impact of the disease. Serious adverse events after yellow fever vaccination are rare. We report the case of a young woman with an unusual presentation of yellow fever 17DD vaccine-associated acute viscerotropic disease, with severe hepatic impairment following a long incubation period. She died more than a month after yellow fever vaccination.

Background Sickle cell disease (SCD) children are frequent travellers to countries where yellow fever (YF) is endemic, but there are no data regarding the safety and immunogenicity of the vaccine in such children treated with hydroxyurea (HU). The main objective of this study was to compare the tolerance and immune response to YF vaccination in SCD children treated or not with HU. Method SCD children Results Among the 52 SCD children vaccinated against YF, 17 (33%) were treated with HU. Only mild adverse events, mainly fever and local reaction, were observed in the HU group with a similar frequency in the non-HU group (57 and 35%, respectively, P = 0.30). YF antibody titres were measured in 15/17 patients in the HU group and 23/35 patients in the non-HU group after a median of 6.0 months (3.5–8.5) following vaccination. The geometric mean of YF antibody titre was similar in both groups. A protective antibody level was observed in 85% of the children in the HU group vs 100% in the non-HU group (P = 0.14), suggesting a lower effectiveness of the vaccine in patients on HU similarly to what has been described in patients on immune suppressive therapy for other vaccines. Conclusion YF vaccination seems to be safe and efficient in SCD children treated with HU. Considering the potential risk of severe complications in cases of YF while travelling in Africa for those patients, the benefit-to-risk ratio argues for YF vaccination in all SCD children. Control of a protective antibody titre may also be useful to ascertain an adequate response in those treated with HU.

To report an unusual case of corneal graft rejection after yellow fever vaccine.Case report.We have described the case of a 48-year-old man who developed a corneal graft rejection in the left eye 3 weeks after a yellow fever vaccination. The ophthalmic examination of the left eye revealed conjunctival hyperemia, corneal graft edema with Descemet folds, and fine keratic precipitates. No abnormalities were found in the right eye. The episode of graft rejection fully recovered after a short course of systemic and topical steroid treatment.This is the first case report of corneal transplant rejection temporally associated with yellow fever vaccination. Although the yellow fever vaccine is a very safe and efficacious vaccine, the occurrence of vaccine-related rejection may be more frequent than reported. Both patients and ophthalmologists should be aware of possible vaccine-related complications which may be potentially sight-threatening.

Dear Editor, As most of us are aware, anti-N-methyl D-aspartate (NMDA) receptor encephalitis is a potentially fatal limbic encephalitis. In several cases, an underlying tumor or a preceding viral infection can be withheld. Sometimes, a previous vaccination seems to precipitate an anti-NMDA receptor encephalitis [...]