Search Results (10)

Background/Objectives: The envelope (E) protein of orthoflaviviruses contains antigenic sites that are composed of one or more epitopes, which can vary in antigenic specificity, including between viral species, strains, and even substrains. Monoclonal antibodies (mAbs) that bind these epitopes vary in functionality based on their specificity. This makes mAbs useful to study the differences in phenotypes between strains of viruses, such as the wild type (WT) and live attenuated vaccine strains of yellow fever virus (YFV). mAb 2D12 was raised against the 17D-204 YFV vaccine substrain virus (YF VAX^®) by Schlesinger et al. in 1983. However, it only neutralizes Asibi WT virus, not the 17D-204 vaccine substrain virus. Results: We confirmed these results and demonstrated that mAb 2D12 fails to neutralize all 17D vaccine substrains (17D-204, 17DD, and 17D-213), indicating that the minor differences between these virus substrains do not affect the epitope or functionality of mAb 2D12. In addition, mAb 2D12 was found to neutralize WT strain of French viscerotropic virus (FVV), with statistically indistinguishable neutralization from the WT strain Asibi. All but one of the live attenuated French neurotropic vaccine (FNV) derivative viruses had significantly lower neutralization than WT strains Asibi and FVV. FVV, Asibi, 17D, and FNV have many amino acid differences in the membrane (M) and E proteins. It is unclear which of them contributes to this differential neutralization. However, FNV and 17D have common amino acid substitutions from WT FVV and Asibi at positions M-36 and E-331, suggesting that one or both of these residues may contribute to the 2D12 epitope. Conclusions: Overall, mAb 2D12 is a valuable tool to distinguish WT virulent strains of YFV from live attenuated vaccine strains. Full article

Background/Objective: Yellow fever (YF) is an acute infectious disease caused by the yellow fever virus which is transmitted by mosquitoes. Neotropical primates are susceptible to infection, which is often presented as epizootic outbreaks. The aim was to evaluate and characterize the immune response against YF in different species of neotropical primates from the Belo Horizonte Zoo. Methods: Vaccine 17DD was administered to 24 neotropical primates, with a single subcutaneous dose. Clinical exams, RNAemia, and detection of IgG and neutralizing antibodies against YFV were performed. In addition, an ethogram was performed to assess clinical changes and animal welfare. Results: At 4 days post-vaccination, RNAemia was detected in nine animals. There was seroconversion and persistence of immune response in Alouatta guariba clamitans, Sapajus xanthosternos, Saguinus imperator and Aotus infulatus. However, the vaccine was not immunogenic for Lagothrix cana. In Pithecia irrorata seroconversion did not persist long term, while the Ateles sp. had a transient immune response. No significant clinical manifestations were observed in any of the vaccinated animals. Conclusions: This study demonstrated a safe, immunogenic and persistent immune response induced by the attenuated 17DD vaccine strain in A. guariba clamitans, S. xanthosternos, S. imperator, and A. infulatus. Full article

Yellow fever (YF) causes severe morbidity and mortality in Africa and South America. It is an arthropod-borne viral disease endemic to tropical regions of Africa and South America. Yellow fever virus (YFV) is transmitted by mosquitoes and frequently affects both non-human primates (NHPs) and humans. Neotropical primates (NTPs) are generally more severely afflicted by YFV than African primates. Asian primates appear not to be susceptible to this disease. Susceptibility varies among NTP species: asymptomatic infections are described in some NTP species, whereas severe epizootic mortality events are described in others. The genus Alouatta (howler monkeys) is considered to be the most susceptible among the NTPs. Epizootic events resulting in the death of thousands of NTPs have been recorded in recent history. As a result, YFV poses a threat to the survival of some NTP species. In most cases, NTPs are found dead without showing prior clinical signs. In cases where clinical signs are observed, they are mostly non-specific. Due to their high susceptibility, epizootic events in NTPs are used as epidemiological predictors for human YF outbreaks. YFV infection may be diagnosed by means of virus isolation, reverse transcription polymerase chain reaction, serology, histopathology, or immunohistochemistry. Animals that survive the disease develop neutralizing antibodies to YFV. Currently, no specific treatment is available. Sustained YF control strategies must rely on surveillance and accurate diagnostics to allow for early detection of outbreaks and rapid implementation of control measures. Prophylaxis should be based on a One Health perspective that recognizes the intricate interplay between human health, primate health, and the environment. Vaccines for YF are available, with the human 17DD vaccine effectively preventing disease in primates. However, mitigation strategies continue to rely more and more on vector control, preferably using eco-friendly methods. Climate change and human activities, and their impact on local ecology, are assumed to increase the risk of YF transmission in the next decades. Full article

Background/Objectives: Yellow fever virus (YFV) (Flaviviridae, Orthoflavivirus) is the etiologic agent of yellow fever (YF), a vector-borne disease with significant morbidity and mortality across the tropics and neotropics, despite having a highly efficacious and safe vaccine (17D). Vaccination provides lifelong protection from YF disease mediated by humoral immunity. There are several versions of the original 17D vaccine: 17D-204 (marketed in the USA as YF-VAX, in France as Stamaril, and in China as Tiantan-V), 17D-213 (Russian Federation), and 17DD (by FIOCRUZ in Brazil). Vaccines produced in the US, France, Senegal, China, and Russia represent 17D-204-derived strains, whereas the Brazilian 17DD has a unique passage/attenuation history from 17D-204-derived strains. Their functional differences in the neutralization profiles are not known. Methods: The Plaque Reduction Neutralization Test (PRNT) was used to determine the neutralization profiles of sera from 209 patients that were previously vaccinated with the 17DD strain against both 17D-204 and 17DD. Results: Sera exhibited significantly more efficient neutralization of 17DD (mean reciprocal PRNT₅₀ 183, PRNT₈₀ 86, median reciprocal PRNT₅₀ 80, and PRNT₈₀ 40) compared to 17D-204 (mean reciprocal PRNT₅₀ 91, PRNT₈₀ 33, median reciprocal PRNT₅₀ 40, and PRNT₈₀ 10). Conclusions: Our data indicate antigenic differences between 17D and 17DD vaccines. Full article

The disease burden of yellow fever virus infection (YFV) is quite high in the tropics where vaccination coverage is low. To date, vaccination is the most effective control strategy to mitigate and eliminate the burden of YF disease. The licensed YF vaccines are safe and effective and serious adverse events are rare. Herein, we report three cases of neurological syndrome, compatible with meningoencephalitis following 17DD vaccination. In all cases, YFV-specific IgM antibodies were detected in the cerebrospinal fluid. Our observations confirm the development of YF vaccine-associated neurotropic disease, a rare serious adverse event, from which all three patients have fully recovered without any long-term sequelae. This report reinforces the need for awareness among health professionals to recognize and effectively manage such events in a timely manner. Full article

The attenuated yellow fever (YF) vaccine is one of the most successful vaccines ever developed. After a single dose administration YF vaccine can induce balanced Th1/Th2 immune responses and long-lasting neutralizing antibodies. These attributes endorsed it as a model of how to properly stimulate the innate response to target protective immune responses. Despite their longstanding success, attenuated YF vaccines can cause rare fatal adverse events and are contraindicated for persons with immunosuppression, egg allergy and age < 6 months and >60 years. These drawbacks have encouraged the development of a non-live vaccine. The aim of the present study is to characterize and compare the immunological profile of two adjuvant formulations of an inactivated YF 17DD vaccine candidate. Inactivated YF vaccine formulations based on alum (Al(OH)₃) or squalene (AddaVax^®) were investigated by immunization of C57BL/6 mice in 3-dose or 2-dose schedules, respectively, and compared with a single dose of attenuated YF virus 17DD. Sera were analyzed by ELISA and Plaque Reduction Neutralization Test (PRNT) for detection of total IgG and neutralizing antibodies against YF virus. In addition, splenocytes were collected to evaluate cellular responses by ELISpot. Both inactivated formulations were able to induce high titers of IgG against YF, although neutralizing antibodies levels were borderline on pre-challenge samples. Analysis of IgG subtypes revealed a predominance of IgG2a associated with improved neutralizing capacity in animals immunized with the attenuated YF vaccine, and a predominance of IgG1 in groups immunized with experimental non-live formulations (alum and AddaVax^®). After intracerebral (IC) challenge, attenuated and inactivated vaccine formulations showed an increase in neutralizing antibodies. The AddaVax^®-based inactivated vaccine and the attenuated vaccine achieved 100% protection, and alum-based equivalent formulation achieved 70% protection. Full article

Beside humans, thousands of non-human primates (NHPs) died during the recent outbreak caused by the yellow fever virus (YFV) in Brazil. Vaccination of NHPs against YFV with the YF 17DD attenuated virus has emerged as a public health strategy, as it would reduce sylvatic transmission while also preserving endangered susceptible species. The hypothesis of establishing an uncontrolled transmission of this attenuated virus in nature was raised. We assessed vector competence of four sylvatic mosquito species, Haemagogus leucocelaenus, Haemagogus janthinomys/capricornii, Sabethes albiprivus, and Sabethes identicus, as well as the urban vector Aedes aegypti for YF 17DD attenuated vaccine virus when fed directly on eleven viremic lion tamarins or artificially challenged with the same virus. No infection was detected in 689 mosquitoes engorged on viremic lion tamarins whose viremia ranged from 1.05 × 10³ to 6.61 × 10³ FFU/mL, nor in those artificially taking ≤ 1 × 10³ PFU/mL. Low viremia presented by YF 17DD-vaccinated New World NHPs combined with the low capacity and null dissemination ability in sylvatic and domestic mosquitoes of this attenuated virus suggest no risk of its transmission in nature. Thus, vaccination of captive and free-living NHPs against YFV is a safe public health strategy. Full article

Yellow Fever disease is caused by the Yellow Fever virus (YFV), an arbovirus from the Flaviviridae family. The re-emergence of Yellow Fever (YF) was facilitated by the increasing urbanization of sylvatic areas, the wide distribution of the mosquito vector, and the low percentage of people immunized in the Americas, which caused severe outbreaks in recent years, with a high mortality rate. Therefore, serological approaches capable of discerning antibodies generated from the wild-type (YFV-WT) strain between the vaccinal strain (YFV-17DD) could facilitate vaccine coverage surveillance, enabling the development of strategies to avoid new outbreaks. In this study, peptides were designed and subjected to microarray procedures with sera collected from individuals infected by WT-YFV and 17DD–YFV of YFV during the Brazilian outbreak of YFV in 2017/2018. From 222 screened peptides, around ten could potentially integrate serological approaches aiming to differentiate vaccinated individuals from naturally infected individuals. Among those peptides, one was synthesized and validated through ELISA. Full article

From 2016 to 2018, Brazil faced the biggest yellow fever (YF) outbreak in the last 80 years, representing a risk of YF reurbanization, especially in megacities. Along with this challenge, the mass administration of the fractionated YF vaccine dose in a naïve population brought another concern: the possibility to increase YF adverse events associated with viscerotropic (YEL-AVD) or neurological disease (YEL-AND). For this reason, we developed a quantitative real time RT-PCR (RT-qPCR) assay based on a duplex TaqMan protocol to distinguish broad-spectrum infections caused by wild-type yellow fever virus (YFV) strain from adverse events following immunization (AEFI) by 17DD strain during the vaccination campaign used to contain this outbreak. A rapid and more accurate RT-qPCR assay to diagnose YFV was established, being able to detect even different YFV genotypes and geographic strains that circulate in Central and South America. Moreover, after testing around 1400 samples from human cases, non-human primates and mosquitoes, we detected just two YEL-AVD cases, confirmed by sequencing, during the massive vaccination in Brazilian Southeast region, showing lower incidence than AEFI as expected. Full article

The yellow fever vaccine (YF17DD) is highly effective with a single injection conferring protection for at least 10 years. The YF17DD induces polyvalent responses, with a TH1/TH2 CD4⁺ profile, robust T CD8⁺ responses, and synthesis of interferon-gamma (IFN-γ), culminating in high titers of neutralizing antibodies. Furthermore, C-type lectin domain containing 5A (CLEC5A) has been implicated in innate outcomes in other flaviviral infections. Here, we conducted a follow-up study in volunteers immunized with YF17DD, investigating the humoral response, cellular phenotypes, gene expression, and single nucleotide polymorphisms (SNPs) of IFNG and CLEC5A, to clarify the role of these factors in early response after vaccination. Activation of CLEC5A⁺ monocytes occurred five days after vaccination (DAV). Following, seven DAV data showed activation of CD4⁺ and CD8⁺T cells together with early positive correlations between type II IFN and genes of innate antiviral response (STAT1, STAT2, IRF7, IRF9, OAS1, and RNASEL) as well as antibody levels. Furthermore, individuals with genotypes rs2430561 AT/AA, rs2069718 AG/AA (IFNG), and rs13237944 AC/AA (CLEC5A), exhibited higher expression of IFNG and CLEC5A, respectively. Together, we demonstrated that early IFN-γ and CLEC5A responses, associated with rs2430561, rs2069718, and rs13237944 genotypes, may be key mechanisms in the long-lasting immunity elicited by YF17DD. Full article