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Learning immunology from the yellow fever vaccine: innate immunity to systems vaccinology.

Despite their great success, we understand little about how effective vaccines stimulate protective immune responses. Two recent developments promise to yield such understanding: the appreciation of the crucial role of the innate immune system in sensing microorganisms and tuning immune responses, and advances in systems biology. Here I review how these developments are yielding insights into the mechanism of action of the yellow fever vaccine, one of the most successful vaccines ever developed, and the broader implications for vaccinology.

Yellow fever mosquito sterol carrier protein-2 gene structure and transcriptional regulation.

AeSCP-2, a sterol carrier protein, is involved in sterol trafficking in mosquitoes. The activity of the AeSCP-2 gene is important for mosquito development. An earlier study demonstrated that the transcription of this gene was upregulated by 20-hydroxyecdysone (20E) in cultured gut tissues. To investigate 20E-regulated transcription of the AeSCP-2 gene we truncated the upstream flanking region of AeSCP-2 gene and linked it to a reporter gene. The mosquito Aag-2 cell line was transfected with these promoter/reporter constructs and treated with 20E at various concentrations. Expression vectors of

Carbon dioxide instantly sensitizes female yellow fever mosquitoes to human skin odours.

Female mosquitoes are noted for their ability to use odours to locate a host for a blood meal. Two sensory organs contribute to their sense of smell: the maxillary palps, which measure the level of CO2, and the antennae, which detect other host-released odours. To establish the relative importance and interactions of CO2 and other body emissions in freely flying mosquitoes, we presented female yellow fever mosquitoes Aedes aegypti L. with broad plumes of human skin odour and CO2 at natural concentrations and dilutions thereof in a wind tunnel. 3-D video-recorded flight tracks were reconstructe…

Genetic variation among strains of wild-type yellow fever virus from Senegal.

We have examined and compared at the molecular level three strains of wild-type yellow fever (YF) virus isolated from Senegal in 1927, 1953 and 1965, termed French viscerotropic virus, Rendu and Dak1279 respectively. Over the structural protein genes, Rendu differed from the other two strains by 8% at the nucleotide level. Rendu also differed antigenically, possessing a 'vaccine'-specific envelope (E) protein epitope (i.e. an epitope previously shown to be found on 17D and French neurotropic vaccine viruses only and not wild-type strains of YF virus). Consequently, we propose that at least two…

South Carolina's last yellow fever epidemic: Manning Simons at Port Royal, 1877.

Throughout the 19th century, yellow fever was the scourge of southern coastal cities. Because of primitive diagnostic tools, differential diagnosis during epidemics was often difficult. Many patients were diagnosed with "malarial fever," breakbone fever, "the prevailing fever," and "mild yellow fever," to name a few. Dr. Manning Simon's opportunity to study an almost "pure" epidemic of yellow fever among an "unacclimated" population was a breakthrough in diagnostic medicine. Fortunately, his findings were not to be needed again in South Carolina, since this was the last outbreak of yellow feve…

Antibody-mediated early death in vivo after infection with yellow fever virus.

The phenomenon known as antibody-dependent enhancement (ADE) has been demonstrated in vitro but its significance in viral pathogenesis is uncertain even though it has been associated with dengue shock syndrome. Here we report for the first time the enhancement of virus virulence in mice using monoclonal antibodies (MAbs) prepared against yellow fever (YF) viruses. Our results show that the average survival time of mice was reduced by up to 33% (i.e. 6.7 to 4.5 days) and that ADE is both antibody dose-dependent and antibody- and virus strain-specific. A total of 12 YF viruses and 11 MAbs were e…

[Sylvatic yellow fever in Africa recent advances and present approach (author's transl)].

Recent works carried out in west and central Africa resulted in numerous yellow fever virus isolations from sylvatic mosquitoes in the forest-savanna transitional zone. This virus was also obtained from monkeys, whereas studies on sequence and duration of the observed epizootics permitted a previsional approach of the yellow fever mechanisms in the same belt, the epidemiological importance of which was stressed ("emergence zone"). In the same course of research and publications, the prevalent part of the involved mosquitoes as virus-reservoirs was constantly emphasized ("reservoir-vector"). Re…

Characterization of an Unusual Severe Yellow Fever Outbreak in the Colombian Andean Region.

BACKGROUND: Yellow fever (YF) reemerged in Colombia's Andean region during 2024-2025, outside the country's historically recognized endemic areas. We characterized critically ill adults admitted during this outbreak and described clinical features, organ dysfunction, supportive care, and in-hospital outcomes. METHODS: We conducted a prospective observational cohort study of consecutive adults with reverse transcription polymerase chain reaction (RT-PCR)-confirmed YF admitted to the national referral intensive care unit in Ibagué, Tolima, Colombia, from March through September 2025. Clinical, …

Mesenteric Ischemia and Bacterial Translocation Precipitate the Intoxication Phase of Yellow Fever.

BACKGROUND: Yellow fever (YF) is classically conceptualized as a hepatotropic disease; indeed, the liver is the primary site of yellow fever virus (YFV) replication. However, circumstantial evidence suggests that extrahepatic disease may be important for the approximately 30% of YF cases that progress to the severe "intoxication" phase of the disease. METHODS: Using a Syrian hamster-adapted (HA) YFV, we worked backwards from observations in humans to examine early events that precipitate the intoxication phase of YF. RESULTS: HA-YFV caused severe disease in approximately 80% of infected anim…

A machine learning approach to identify at-risk populations for yellow fever vaccination.

INTRODUCTION: Vaccinations play a crucial role in public and personal health. Vaccines such as the Yellow Fever 17D vaccine are effective at preventing disease and provide lifelong immunity with few adverse events. Leveraging the increase in electronic medical records and the widespread use of machine learning algorithms in healthcare, this study aims to investigate and develop an algorithmic framework for analyzing clinical data on Yellow Fever 17D vaccinations in order to predict at-risk populations for adverse events following immunizations. This research incorporates parameters from the pa…

Эволюция и побочная динамика желтой лихорадки на стыке между лесами и городами в Бразилии.

Вирус желтой лихорадки (YFV) продолжает угрожать людям и животным на Американском континенте, однако его передача на стыке между лесами и городами остается неясной. Здесь мы сочетаем наблюдение за комарами на уровне земли и полога, систематический мониторинг нечеловеческих приматов и вирусных метагеномиков для описания динамики вспышки сильватического YFV в фрагменте 186-гектара Атлантического леса, встроенного в город Сан-Паулу, Бразилия, в период с 2017 по 2018 год. Проведенный нами анализ показывает, что передача была главным образом вызвана одним генетическим кластером, созданным в период

Совпадение в аннотации оригинала
Yellow fever virus (YFV) continues to threaten human and wildlife populations in the Americas, yet its transmission at the forest-urban interface remains unclear. Here we integrate ground- and canopy-level mosquito surveillance, systematic monitoring of non-human primate carcasses and viral metagenomics to describe the dynamics of a sylvatic YFV outbreak in …

Количественная оценка Желтого Вируса Желтой Железной Железной Жемчужины по Плэк Ассайз и Фокус Формэйшн Ассайз.

Способность вируса желтой лихорадки вторгнуться в клетку хозяина и реплицировать себя является важным свойством, которое позволяет нам подсчитать нагрузку инфекционных частиц. Наиболее распространенным методом количественной оценки заразности цитопатических вирусов является доска. В табличке дается количественная оценка количества формирующихся на табличках (PFU) в образце вируса. Анализы вирусных вирусов на основе клеток полезны для диагностики вирусов и на различных этапах разработки вакцин. В этой главе будет подробно описан протокол для определения мощности вируса желтой лихорадки в лабора

Совпадение в аннотации оригинала
The yellow fever virus' ability to invade the host cell and replicate itself is an important property that allows us to quantify the load of infectious particles. The most-common method for quantifying the infectivity of cytopathic viruses is the plaque assay. The plaque assay quantifies the number of plaque-forming units (PFU) in a virus sample. Cell-based …

Timeliness of Yellow Fever Specimen Collection and Transport in Ghana, 2018-2022.

Yellow fever is a mosquito-borne viral hemorrhagic fever that has caused recent outbreaks in African countries, including Ghana (2021-2022). Delayed diagnosis of yellow fever may cause increased morbidity and mortality. To improve timely detection of yellow fever, we need to better understand the factors contributing to diagnostic delays. We analyzed the diagnostic testing timeline of all suspected yellow fever cases in Ghana from 2018-2022. For these patients we calculated the days from symptom onset to specimen collection and arrival at the National Public Health and Reference Laboratory (NP…