RESUMEN
The present study aimed at investigating whether the hydroxychloroquine (HCQ) treatment would impact the neutralizing antibody production, viremia levels and the kinetics of serum soluble mediators upon planned 17DD-Yellow Fever (YF) primovaccination (Bio-Manguinhos-FIOCRUZ) of primary Sjögren's syndrome (pSS). A total of 34 pSS patients and 23 healthy controls (HC) were enrolled. The pSS group was further categorized according to the use of HCQ (HCQ and Non-HCQ). The YF-plaque reduction neutralization test (PRNT ≥1:50), YF viremia (RNAnemia) and serum biomarkers analyses were performed at baseline and subsequent time-points (Day0/Day3-4/Day5-6/Day7/Day14-D28). The pSS group showed PRNT titers and seropositivity rates similar to those observed for HC (GeoMean = 238 vs 440, p = .11; 82% vs 96%, p = .13). However, the HCQ subgroup exhibited lower seroconversion rates as compared to HC (GeoMean = 161 vs 440, p = .04; 69% vs 96%, p = .02) and Non-HQC (GeoMean = 161 vs 337, p = .582; 69% vs 94%, p = .049). No differences in YF viremia were observed amongst subgroups. Serum biomarkers analyses demonstrated that HCQ subgroup exhibited increased levels of CCL2, CXL10, IL-6, IFN-γ, IL1-Ra, IL-9, IL-10, and IL-2 at baseline and displayed a consistent increase of several biomarkers along the kinetics timeline up to D14-28. These results indicated that HCQ subgroup exhibited a deficiency in assembling YF-specific immune response elicited by 17DD-YF primovaccination as compared to Non-HCQ subgroup. Our findings suggested that hydroxychloroquine is associated with a decrease in the humoral immune response after 17DD-YF primovaccination.
Asunto(s)
Anticuerpos Neutralizantes , Anticuerpos Antivirales , Hidroxicloroquina , Seroconversión , Síndrome de Sjögren , Fiebre Amarilla , Humanos , Hidroxicloroquina/uso terapéutico , Síndrome de Sjögren/tratamiento farmacológico , Síndrome de Sjögren/inmunología , Femenino , Persona de Mediana Edad , Masculino , Adulto , Fiebre Amarilla/inmunología , Fiebre Amarilla/prevención & control , Anticuerpos Antivirales/sangre , Anticuerpos Neutralizantes/sangre , Vacuna contra la Fiebre Amarilla/inmunología , Anciano , Viremia/tratamiento farmacológico , Viremia/inmunología , Virus de la Fiebre Amarilla/inmunología , Citocinas/sangre , Biomarcadores/sangreRESUMEN
Little is known about the frequency of Zika virus (ZIKV) infections in Sudan. The aim of this study was to obtain data on the prevalence of ZIKV infections and the immunity of the population in the country. To this end, 198 sera obtained between December 2012 and January 2013 in different regions in Sudan were examined for neutralizing antibodies against ZIKV, dengue virus (DENV), and yellow fever virus (YFV). The sera were non-randomly selected. The neutralization titers were compared with each other and with the WHO 1st International Standard for anti-Asian lineage Zika virus antibody. Twenty-six sera neutralized ZIKV. One-third of these sera had higher neutralization titers against ZIKV than against DENV-2 and -3. Two sera showed higher neutralization titers than the WHO standard for ZIKV antibodies. These data suggest occasional ZIKV infections in Sudan. The low percentage of sera in this cohort that neutralized ZIKV indicates that, in the study period, the population was susceptible to ZIKV infection.
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Anticuerpos Neutralizantes , Anticuerpos Antivirales , Infección por el Virus Zika , Virus Zika , Sudán/epidemiología , Humanos , Infección por el Virus Zika/epidemiología , Infección por el Virus Zika/inmunología , Infección por el Virus Zika/sangre , Anticuerpos Antivirales/sangre , Virus Zika/inmunología , Anticuerpos Neutralizantes/sangre , Anticuerpos Neutralizantes/inmunología , Adulto , Femenino , Masculino , Persona de Mediana Edad , Adulto Joven , Adolescente , Pruebas de Neutralización , Virus del Dengue/inmunología , Niño , Virus de la Fiebre Amarilla/inmunología , Estudios Seroepidemiológicos , Preescolar , Anciano , PrevalenciaRESUMEN
Yellow fever virus (YFV) is endemic in >40 countries and causes viscerotropic disease with up to 20%-60% mortality. Successful live-attenuated yellow fever (YF) vaccines were developed in the mid-1930s, but their use is restricted or formally contraindicated in vulnerable populations including infants, the elderly, and people with compromised immune systems. In these studies, we describe the development of a next-generation hydrogen peroxide-inactivated YF vaccine and determine immune correlates of protection based on log neutralizing index (LNI) and neutralizing titer-50% (NT50) studies. In addition, we compare neutralizing antibody responses and protective efficacy of hydrogen peroxide-inactivated YF vaccine candidates to live-attenuated YFV-17D (YF-VAX) in a rhesus macaque model of viscerotropic YF. Our results indicate that an optimized, inactivated YF vaccine elicits protective antibody responses that prevent viral dissemination and lethal infection in rhesus macaques and may be a suitable alternative for vaccinating vulnerable populations who are not eligible to receive replicating live-attenuated YF vaccines.
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Anticuerpos Neutralizantes , Anticuerpos Antivirales , Modelos Animales de Enfermedad , Peróxido de Hidrógeno , Macaca mulatta , Vacunas de Productos Inactivados , Vacuna contra la Fiebre Amarilla , Fiebre Amarilla , Virus de la Fiebre Amarilla , Animales , Vacunas de Productos Inactivados/inmunología , Vacuna contra la Fiebre Amarilla/inmunología , Fiebre Amarilla/prevención & control , Fiebre Amarilla/inmunología , Virus de la Fiebre Amarilla/inmunología , Anticuerpos Neutralizantes/inmunología , Anticuerpos Antivirales/inmunología , Vacunas Atenuadas/inmunología , Chlorocebus aethiops , Células Vero , HumanosRESUMEN
The complete lack of yellow fever virus (YFV) in Asia, and the lack of urban YFV transmission in South America, despite the abundance of the peridomestic mosquito vector Aedes (Stegomyia.) aegypti is an enigma. An immunologically naïve population of over 2 billion resides in Asia, with most regions infested with the urban YF vector. One hypothesis for the lack of Asian YF, and absence of urban YF in the Americas for over 80 years, is that prior immunity to related flaviviruses like dengue (DENV) or Zika virus (ZIKV) modulates YFV infection and transmission dynamics. Here we utilized an interferon α/ß receptor knock-out mouse model to determine the role of pre-existing dengue-2 (DENV-2) and Zika virus (ZIKV) immunity in YF virus infection, and to determine mechanisms of cross-protection. We utilized African and Brazilian YF strains and found that DENV-2 and ZIKV immunity significantly suppresses YFV viremia in mice, but may or may not protect relative to disease outcomes. Cross-protection appears to be mediated mainly by humoral immune responses. These studies underscore the importance of re-assessing the risks associated with YF outbreak while accounting for prior immunity from flaviviruses that are endemic.
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Protección Cruzada , Virus del Dengue , Modelos Animales de Enfermedad , Ratones Noqueados , Receptor de Interferón alfa y beta , Fiebre Amarilla , Virus de la Fiebre Amarilla , Infección por el Virus Zika , Virus Zika , Animales , Fiebre Amarilla/inmunología , Fiebre Amarilla/prevención & control , Fiebre Amarilla/virología , Ratones , Protección Cruzada/inmunología , Virus de la Fiebre Amarilla/inmunología , Virus Zika/inmunología , Infección por el Virus Zika/inmunología , Infección por el Virus Zika/prevención & control , Infección por el Virus Zika/virología , Virus del Dengue/inmunología , Receptor de Interferón alfa y beta/genética , Receptor de Interferón alfa y beta/deficiencia , Anticuerpos Antivirales/inmunología , Anticuerpos Antivirales/sangre , Flavivirus/inmunología , Aedes/virología , Aedes/inmunología , Dengue/inmunología , Dengue/prevención & control , Dengue/virología , Femenino , Viremia/inmunología , Mosquitos Vectores/virología , Mosquitos Vectores/inmunología , Infecciones por Flavivirus/inmunología , Infecciones por Flavivirus/prevención & control , Infecciones por Flavivirus/virología , Ratones Endogámicos C57BLRESUMEN
Memory T cells are conventionally associated with durable recall responses. In our longitudinal analyses of CD4+ T cell responses to the yellow fever virus (YFV) vaccine by peptide-MHC tetramers, we unexpectedly found CD45RO-CCR7+ virus-specific CD4+ T cells that expanded shortly after vaccination and persisted months to years after immunization. Further phenotypic analyses revealed the presence of stem cell-like memory T cells within this subset. In addition, after vaccination T cells lacking known memory markers and functionally resembling genuine naive T cells were identified, referred to herein as marker-negative T (TMN) cells. Single-cell TCR sequencing detected expanded clonotypes within the TMN subset and identified TMN TCRs shared with memory and effector T cells. Longitudinal tracking of YFV-specific responses over subsequent years revealed superior stability of TMN cells, which correlated with the longevity of the overall tetramer+ population. These findings uncover additional complexity within the post-immune T cell compartment and implicate TMN cells in durable immune responses.
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Linfocitos T CD4-Positivos , Células T de Memoria , Vacunación , Vacuna contra la Fiebre Amarilla , Humanos , Linfocitos T CD4-Positivos/inmunología , Vacuna contra la Fiebre Amarilla/inmunología , Células T de Memoria/inmunología , Virus de la Fiebre Amarilla/inmunología , Masculino , Femenino , Memoria Inmunológica/inmunología , Fiebre Amarilla/inmunología , Fiebre Amarilla/prevención & control , Adulto , Estudios Longitudinales , FenotipoRESUMEN
Yellow fever outbreaks are prevalent, particularly in endemic regions. Given the lack of an established treatment for this disease, significant attention has been directed toward managing this arbovirus. In response, we developed a multiepitope vaccine designed to elicit an immune response, utilizing advanced immunoinformatic and molecular modeling techniques. To achieve this, we predicted B- and T-cell epitopes using the sequences from all structural (E, prM, and C) and nonstructural proteins of 196 YFV strains. Through comprehensive analysis, we identified 10 cytotoxic T-lymphocyte (CTL) and 5T-helper (Th) epitopes that exhibited overlap with B-lymphocyte epitopes. These epitopes were further evaluated for their affinity to a wide range of human leukocyte antigen system alleles and were rigorously tested for antigenicity, immunogenicity, allergenicity, toxicity, and conservation. These epitopes were linked to an adjuvant ( ß -defensin) and to each other using ligands, resulting in a vaccine sequence with appropriate physicochemical properties. The 3D structure of this sequence was created, improved, and quality checked; then it was anchored to the Toll-like receptor. Molecular Dynamics and Quantum Mechanics/Molecular Mechanics simulations were employed to enhance the accuracy of docking calculations, with the QM portion of the simulations carried out utilizing the density functional theory formalism. Moreover, the inoculation model was able to provide an optimal codon sequence that was inserted into the pET-28a( +) vector for in silico cloning and could even stimulate highly relevant humoral and cellular immunological responses. Overall, these results suggest that the designed multi-epitope vaccine can serve as prophylaxis against the yellow fever virus.
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Epítopos de Linfocito T , Vacuna contra la Fiebre Amarilla , Fiebre Amarilla , Virus de la Fiebre Amarilla , Vacuna contra la Fiebre Amarilla/inmunología , Virus de la Fiebre Amarilla/inmunología , Virus de la Fiebre Amarilla/genética , Humanos , Fiebre Amarilla/prevención & control , Fiebre Amarilla/inmunología , Epítopos de Linfocito T/inmunología , Epítopos de Linfocito B/inmunología , Vacunología/métodos , Modelos Moleculares , Desarrollo de Vacunas , Simulación de Dinámica Molecular , Linfocitos T Citotóxicos/inmunologíaRESUMEN
In our study, we developed a point of care electrochemical biosensing platform based on the functionalized cysteine-positioned gold electrode to diagnose yellow fever disease from human plasma samples. The developed platform underwent characterization through diverse methods encompassing cyclic voltammetry, electrochemical impedance spectroscopy, scanning electron microscopy, energy dispersive X-ray spectroscopy, and density-functional theory. The capacitive interaction between yellow fever virus non-structural antigen and antibody gave a cathodic signal at approximately -260 mV, and increased in proportion to the amount of non-structural antibody. The created electrochemical biosensor has an ability to detect 96 ag/mL of the yellow fever non-structural antibody with an extensive analytical range varied from 0.1 fg/mL to 1 µg/mL. The interference effects of various substances that could be found in human plasma, and the performance of the method were examined from the point of recovery and relative standard deviation for human plasma samples; hereby, the results confirmed the unprecedented selectivity and accuracy of the proposed method.
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Técnicas Biosensibles , Técnicas Electroquímicas , Proteínas no Estructurales Virales , Fiebre Amarilla , Humanos , Técnicas Biosensibles/métodos , Fiebre Amarilla/diagnóstico , Fiebre Amarilla/sangre , Fiebre Amarilla/inmunología , Fiebre Amarilla/virología , Proteínas no Estructurales Virales/inmunología , Proteínas no Estructurales Virales/sangre , Técnicas Electroquímicas/métodos , Sistemas de Atención de Punto , Virus de la Fiebre Amarilla/inmunología , Teoría Funcional de la Densidad , Electrodos , Anticuerpos Antivirales/sangre , Anticuerpos Antivirales/inmunología , Oro/químicaRESUMEN
Live-attenuated yellow fever vaccine (YF17D) was developed in the 1930s as the first ever empirically derived human vaccine. Ninety years later, it is still a benchmark for vaccines made today. YF17D triggers a particularly broad and polyfunctional response engaging multiple arms of innate, humoral and cellular immunity. This unique immunogenicity translates into an extraordinary vaccine efficacy and outstanding longevity of protection, possibly by single-dose immunization. More recently, progress in molecular virology and synthetic biology allowed engineering of YF17D as a powerful vector and promising platform for the development of novel recombinant live vaccines, including two licensed vaccines against Japanese encephalitis and dengue, even in paediatric use. Likewise, numerous chimeric and transgenic preclinical candidates have been described. These include prophylactic vaccines against emerging viral infections (e.g. Lassa, Zika and SARS-CoV-2) and parasitic diseases (e.g. malaria), as well as therapeutic applications targeting persistent infections (e.g. HIV and chronic hepatitis), and cancer. Efforts to overcome historical safety concerns and manufacturing challenges are ongoing and pave the way for wider use of YF17D-based vaccines. In this review, we summarize recent insights regarding YF17D as vaccine platform, and how YF17D-based vaccines may complement as well as differentiate from other emerging modalities in response to unmet medical needs and for pandemic preparedness.
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Vacunas Atenuadas , Vacuna contra la Fiebre Amarilla , Virus de la Fiebre Amarilla , Humanos , Vacuna contra la Fiebre Amarilla/inmunología , Virus de la Fiebre Amarilla/inmunología , Vacunas Atenuadas/inmunología , Animales , Fiebre Amarilla/prevención & control , Fiebre Amarilla/inmunología , Vacunación/métodosRESUMEN
The non-human primate (NHP) model (specifically rhesus and cynomolgus macaques) has facilitated our understanding of the pathogenic mechanisms of yellow fever (YF) disease and allowed the evaluation of the safety and efficacy of YF-17D vaccines. However, the accuracy of this model in mimicking vaccine-induced immunity in humans remains to be fully determined. We used a systems biology approach to compare hematological, biochemical, transcriptomic, and innate and antibody-mediated immune responses in cynomolgus macaques and human participants following YF-17D vaccination. Immune response progression in cynomolgus macaques followed a similar course as in adult humans but with a slightly earlier onset. Yellow fever virus neutralizing antibody responses occurred earlier in cynomolgus macaques [by Day 7[(D7)], but titers > 10 were reached in both species by D14 post-vaccination and were not significantly different by D28 [plaque reduction neutralization assay (PRNT)50 titers 3.6 Log vs 3.5 Log in cynomolgus macaques and human participants, respectively; P = 0.821]. Changes in neutrophils, NK cells, monocytes, and T- and B-cell frequencies were higher in cynomolgus macaques and persisted for 4 weeks versus less than 2 weeks in humans. Low levels of systemic inflammatory cytokines (IL-1RA, IL-8, MIP-1α, IP-10, MCP-1, or VEGF) were detected in either or both species but with no or only slight changes versus baseline. Similar changes in gene expression profiles were elicited in both species. These included enriched and up-regulated type I IFN-associated viral sensing, antiviral innate response, and dendritic cell activation pathways D3-D7 post-vaccination in both species. Hematological and blood biochemical parameters remained relatively unchanged versus baseline in both species. Low-level YF-17D viremia (RNAemia) was transiently detected in some cynomolgus macaques [28% (5/18)] but generally absent in humans [except one participant (5%; 1/20)].IMPORTANCECynomolgus macaques were confirmed as a valid surrogate model for replicating YF-17D vaccine-induced responses in humans and suggest a key role for type I IFN.
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Macaca fascicularis , Modelos Animales , Vacuna contra la Fiebre Amarilla , Animales , Femenino , Humanos , Masculino , Anticuerpos Neutralizantes/sangre , Anticuerpos Neutralizantes/inmunología , Anticuerpos Antivirales/sangre , Anticuerpos Antivirales/inmunología , Inmunidad Innata , Biología de Sistemas/métodos , Vacunación , Fiebre Amarilla/prevención & control , Fiebre Amarilla/inmunología , Fiebre Amarilla/virología , Vacuna contra la Fiebre Amarilla/inmunología , Virus de la Fiebre Amarilla/inmunologíaRESUMEN
Yellow fever (YF) is one of the most acute viral hemorrhagic diseases of the 18th and 19th centuries, which continues to cause severe morbidity and mortality in Africa. After 21 years of no reported cases of yellow fever in Nigeria, till 2017 where a case was confirmed in Kwara State, also in November 2018,WHO was informed of a cluster of suspected yellow fever cases and deaths in Edo state, Nigeria. The study was among all age group attending health centres in Benin City, Edo state. A total of 280 blood samples were collected from consented febrile patients and were screened for antibodies to Zika virus using rapid diagnostic test (RDT) kits. Blood samples positive to Zika virus (IgM/IgG RDT), were subjected to molecular characterization. Using the flavividae family primers, six (6) samples where confirmed positive by Hemi-nested reverse transcription PCR (hnRT-PCR) sequencing. Nucleotide sequence blast revealed the sequenceswere similar to Yellow fever virus strains. Phylogenetic analysis revealed that the yellow fever virus sequences are closely related to the African strains. Despite the safe and effective yellow fever vaccine, yellow fever virus is seen to be in circulation, hence the need for continues mass vaccination.
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Filogenia , Fiebre Amarilla , Virus de la Fiebre Amarilla , Humanos , Nigeria/epidemiología , Virus de la Fiebre Amarilla/genética , Virus de la Fiebre Amarilla/inmunología , Fiebre Amarilla/epidemiología , Fiebre Amarilla/virología , Fiebre Amarilla/sangre , Adulto , Femenino , Masculino , Adolescente , Persona de Mediana Edad , Niño , Preescolar , Adulto Joven , Anticuerpos Antivirales/sangre , Anticuerpos Antivirales/inmunología , Lactante , Virus Zika/genética , Virus Zika/inmunología , Virus Zika/aislamiento & purificaciónRESUMEN
Between 2016 and 2018, Brazil experienced major sylvatic yellow fever (YF) outbreaks that caused hundreds of casualties, with Minas Gerais (MG) being the most affected state. These outbreaks provided a unique opportunity to assess the immune response triggered by the wild-type (WT) yellow fever virus (YFV) in humans. The plaque reduction neutralization test (PRNT) is currently the standard method to assess the humoral immune response to YFV by measuring neutralizing antibodies (nAbs). The present study aimed to evaluate the humoral immune response of patients from the 2017-2018 sylvatic YF outbreak in MG with different disease outcomes by using PRNTs with a WT YFV strain, isolated from the 2017-2018 outbreak, and a vaccine YFV strain. Samples from naturally infected YF patients were tested, in comparison with healthy vaccinees. Results showed that both groups presented different levels of nAb against the WT and vaccine strains, and the levels of neutralization against the strains varied homotypically and heterotypically. Results based on the geometric mean titers (GMTs) suggest that the humoral immune response after a natural infection of YFV can reach higher levels than that induced by vaccination (GMT of patients against WT YFV compared to GMT of vaccinees, P < 0.0001). These findings suggest that the humoral immune responses triggered by the vaccine and WT strains of YFV are different, possibly due to genetic and antigenic differences between these viruses. Therefore, current means of assessing the immune response in naturally infected YF individuals and immunological surveillance methods in areas with intense viral circulation may need to be updated.IMPORTANCEYellow fever is a deadly febrile disease caused by the YFV. Despite the existence of effective vaccines, this disease still represents a public health concern worldwide. Much is known about the immune response against the vaccine strains of the YFV, but recent studies have shown that it differs from that induced by WT strains. The extent of this difference and the mechanisms behind it are still unclear. Thus, studies aimed to better understand the immune response against this virus are relevant and necessary. The present study evaluated levels of neutralizing antibodies of yellow fever patients from recent outbreaks in Brazil, in comparison with healthy vaccinees, using plaque reduction neutralization tests with WT and vaccine YFV strains. Results showed that the humoral immune response in naturally infected patients was higher than that induced by vaccination, thus providing new insights into the immune response triggered against these viruses.
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Anticuerpos Neutralizantes , Anticuerpos Antivirales , Brotes de Enfermedades , Inmunidad Humoral , Vacuna contra la Fiebre Amarilla , Fiebre Amarilla , Virus de la Fiebre Amarilla , Fiebre Amarilla/inmunología , Fiebre Amarilla/epidemiología , Fiebre Amarilla/virología , Humanos , Brasil/epidemiología , Virus de la Fiebre Amarilla/inmunología , Virus de la Fiebre Amarilla/genética , Anticuerpos Neutralizantes/sangre , Anticuerpos Neutralizantes/inmunología , Anticuerpos Antivirales/sangre , Anticuerpos Antivirales/inmunología , Masculino , Vacuna contra la Fiebre Amarilla/inmunología , Femenino , Adulto , Persona de Mediana Edad , Vacunación , Pruebas de Neutralización , Adulto Joven , Anciano , AdolescenteRESUMEN
BACKGROUND: Vaccination plays a critical role in mitigating the burden associated with yellow fever (YF). However, there is a lack of comprehensive evidence on the humoral response to primary vaccination in the paediatric population, with several questions debated, including the response when the vaccine is administered at early ages, the effect of co-administration with other vaccines, the duration of immunity and the use of fractional doses, among others. This study summarizes the existing evidence regarding the humoral response to primary YF vaccination in infants and children. METHODS: Studies on the humoral response to primary YF vaccination in children aged 12 years or younger were reviewed. The humoral vaccine response rate (VRR), i.e. the proportion of children who tested positive for vaccine-induced YF-specific neutralizing antibodies, was pooled through random-effects meta-analysis and categorized based on the time elapsed since vaccination. Subgroup, meta-regression and sensitivity analyses were performed. RESULTS: A total of 33 articles met the inclusion criteria, with all but one conducted in countries where YF is endemic. A total of 14 028 infants and children entered this systematic review. Within three months following vaccination, the pooled VRR was 91.9% (95% CI 89.8-93.9). A lower VRR was observed with the 17DD vaccine at the meta-regression analysis. No significant differences in immunogenicity outcomes were observed based on age, administration route, co-administration with other vaccines, or fractional dosing. Results also indicate a decline in VRR over time. CONCLUSIONS: Primary YF vaccination effectively provides humoral immunity in paediatric population. However, humoral response declines over time, and this decline is observable after the first 18 months following vaccination. A differential response according to the vaccine substrain was also observed. This research has valuable implications for stimulating further research on the primary YF vaccination in infants and children, as well as for informing future policies.
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Vacuna contra la Fiebre Amarilla , Fiebre Amarilla , Humanos , Vacuna contra la Fiebre Amarilla/inmunología , Vacuna contra la Fiebre Amarilla/administración & dosificación , Fiebre Amarilla/prevención & control , Fiebre Amarilla/inmunología , Lactante , Niño , Preescolar , Inmunidad Humoral , Vacunación/métodos , Inmunogenicidad Vacunal , Anticuerpos Antivirales/sangre , Virus de la Fiebre Amarilla/inmunologíaAsunto(s)
Vacuna contra la Fiebre Amarilla , Fiebre Amarilla , Humanos , Vacuna contra la Fiebre Amarilla/inmunología , Vacuna contra la Fiebre Amarilla/administración & dosificación , Fiebre Amarilla/prevención & control , Fiebre Amarilla/inmunología , Inmunogenicidad Vacunal , Anticuerpos Antivirales/sangre , Virus de la Fiebre Amarilla/inmunologíaRESUMEN
BACKGROUND: In 2016, outbreaks of yellow fever in Angola and the Democratic Republic of the Congo led to a global vaccine shortage. A fractional dose of 17DD yellow fever vaccine (containing one-fifth [0·1 ml] of the standard dose) was used during a pre-emptive mass campaign in August, 2016, in Kinshasa, Democratic Republic of the Congo among children aged 2 years and older and non-pregnant adults (ie, those aged 18 years and older). 1 year following vaccination, 97% of participants were seropositive; however, the long-term durability of the immune response is unknown. We aimed to conduct a prospective cohort study and invited participants enrolled in the previous evaluation to return 5 years after vaccination to assess durability of the immune response. METHODS: Participants returned to one of six health facilities in Kinshasa in 2021, where study staff collected a brief medical history and blood specimen. We assessed neutralising antibody titres against yellow fever virus using a plaque reduction neutralisation test with a 50% cutoff (PRNT50). Participants with a PRNT50 titre of 10 or higher were considered seropositive. The primary outcome was the proportion of participants seropositive at 5 years. FINDINGS: Among the 764 participants enrolled, 566 (74%) completed the 5-year visit. 5 years after vaccination, 539 (95·2%, 95% CI 93·2-96·7) participants were seropositive, including 361 (94·3%, 91·5-96·2) of 383 who were seronegative and 178 (97·3%, 93·8-98·8) of 183 who were seropositive at baseline. Geometric mean titres (GMTs) differed significantly across age groups for those who were initially seronegative with the lowest GMT among those aged 2-5 years and highest among those aged 13 years and older. INTERPRETATION: A fractional dose of the 17DD yellow fever vaccine induced an immunologic response with detectable titres at 5 years among the majority of participants in the Democratic Republic of the Congo. These findings support the use of fractional-dose vaccination for outbreak prevention with the potential for sustained immunity. FUNDING: Gavi, the Vaccine Alliance through the CDC Foundation. TRANSLATION: For the French translation of the abstract see Supplementary Materials section.
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Anticuerpos Antivirales , Brotes de Enfermedades , Vacuna contra la Fiebre Amarilla , Fiebre Amarilla , Humanos , República Democrática del Congo/epidemiología , Fiebre Amarilla/prevención & control , Fiebre Amarilla/inmunología , Fiebre Amarilla/epidemiología , Estudios Prospectivos , Vacuna contra la Fiebre Amarilla/inmunología , Vacuna contra la Fiebre Amarilla/administración & dosificación , Brotes de Enfermedades/prevención & control , Masculino , Femenino , Niño , Preescolar , Adolescente , Adulto , Anticuerpos Antivirales/sangre , Adulto Joven , Vacunación , Persona de Mediana Edad , Anticuerpos Neutralizantes/sangre , Virus de la Fiebre Amarilla/inmunologíaAsunto(s)
Genoma Viral , Vacuna contra la Fiebre Amarilla , Fiebre Amarilla , Virus de la Fiebre Amarilla , Humanos , Virus de la Fiebre Amarilla/genética , Virus de la Fiebre Amarilla/inmunología , Fiebre Amarilla/prevención & control , Fiebre Amarilla/inmunología , Vacuna contra la Fiebre Amarilla/efectos adversos , Vacuna contra la Fiebre Amarilla/inmunología , Masculino , FilogeniaAsunto(s)
Humanos , Animales , Fiebre Amarilla/prevención & control , Virus de la Fiebre Amarilla/inmunología , Vacuna contra la Fiebre Amarilla/inmunología , Fiebre Amarilla/transmisión , Fiebre Amarilla/epidemiología , Fiebre Amarilla/virología , Virus de la Fiebre Amarilla/genética , Brasil/epidemiología , Vacunas Atenuadas/administración & dosificación , Vacunas Atenuadas/genética , Vacunas Atenuadas/inmunología , Aedes/fisiología , Aedes/virología , Vacuna contra la Fiebre Amarilla/administración & dosificación , Vacuna contra la Fiebre Amarilla/genéticaRESUMEN
Abstract INTRODUCTION: Pseudo-infectious yellow fever viral particles (YFV-PIVs) have been used to study vaccines and viral packaging. Here, we report the development of a packaging cell line, which expresses the YFV prM/E proteins. METHODS: HEK293 cells were transfected with YFV prM/E and C (84 nt) genes to generate HEK293-YFV-PrM/E-opt. The cells were evaluated for their ability to express the heterologous proteins and to package the replicon repYFV-17D-LucIRES, generating YFV-PIVs. RESULTS: The expression of prM/E proteins was confirmed, and the cell line trans-packaged the replicon for recovery of a reporter for the YFV-PIVs. CONCLUSIONS: HEK293-YFV-prM/E-opt trans-packaging capacity demonstrates its possible biotechnology application.
Asunto(s)
Humanos , Replicación Viral/inmunología , Virus de la Fiebre Amarilla/inmunología , Ensamble de Virus/inmunología , Vacunas de Partículas Similares a Virus/inmunología , Replicación Viral/genética , Virus de la Fiebre Amarilla/genética , Ensamble de Virus/genética , Técnica del Anticuerpo Fluorescente Indirecta , Proteínas Fluorescentes Verdes , Células HEK293 , Vacunas de Partículas Similares a Virus/genética , Citometría de FlujoRESUMEN
The yellow fever (YF) vaccine has been used since the 1930s to prevent YF, which is a severe infectious disease caused by the yellow fever virus (YFV), and mainly transmitted by Culicidae mosquitoes from the genera Aedes and Haemagogus . Until 2013, the World Health Organization (WHO) recommended the administration of a vaccine dose every ten years. A new recommendation of a single vaccine dose to confer life-long protection against YFV infection has since been established. Recent evidence published elsewhere suggests that at least a second dose is needed to fully protect against YF disease. Here, we discuss the feasibility of administering multiple doses, the necessity for a new and modern vaccine, and recommend that the WHO conveys a meeting to discuss YFV vaccination strategies for people living in or travelling to endemic areas.
Asunto(s)
Humanos , Fiebre Amarilla/prevención & control , Virus de la Fiebre Amarilla/inmunología , Esquemas de Inmunización , Anticuerpos Neutralizantes/inmunología , Vacuna contra la Fiebre Amarilla/administración & dosificación , Vacuna contra la Fiebre Amarilla/inmunologíaRESUMEN
ABSTRACT Introduction: The World Health Organization (WHO) recommends one single dose of the Yellow Fever (YF) vaccine based on studies of antibody persistency in healthy adults. We assessed the prevalence and titers of YF virus neutralizing antibodies in previously vaccinated persons aged ≥ 60 years, in comparison to younger adults. We also evaluated the correlation between antibody titers and the time since vaccination among participants who received one vaccine dose, and the seropositivity among participants vaccinated prior to or within the past 10 years. Methods: previously vaccinated healthy persons aged ≥ 18 years were included. YF virus neutralizing antibody titers were determined by means of the 50% Plaque Reduction Neutralization Test. Results: 46 persons aged ≥ 60 years and 48 persons aged 18 to 59 years were enrolled. There was no significant difference in the prevalence of YF virus neutralizing antibodies between the two groups (p = 0.263). However, titers were significantly lower in the elderly (p = 0.022). There was no correlation between YF virus neutralizing antibody titers and the time since vaccination. There was no significant difference in seropositivity among participants vaccinated prior to or within the past 10 years. Conclusions: the clinical relevance of the observed difference in YF virus neutralizing antibody titers between the two groups is not clear.
Asunto(s)
Humanos , Masculino , Femenino , Adolescente , Adulto , Persona de Mediana Edad , Anciano , Adulto Joven , Anticuerpos Neutralizantes/sangre , Anticuerpos Antivirales/sangre , Vacuna contra la Fiebre Amarilla/inmunología , Virus de la Fiebre Amarilla/inmunología , Fiebre Amarilla/prevención & control , Factores de Edad , Brasil , Inmunoglobulina M/sangre , Fiebre Amarilla/inmunologíaRESUMEN
This randomised, double-blind, multicentre study with children nine-23 months old evaluated the immunogenicity of yellow fever (YF) vaccines prepared with substrains 17DD and 17D-213/77. YF antibodies were tittered before and 30 or more days after vaccination. Seropositivity and seroconversion were analysed according to the maternal serological status and the collaborating centre. A total of 1,966 children were randomised in the municipalities of the states of Mato Grosso do Sul, Minas Gerais and São Paulo and blood samples were collected from 1,714 mothers. Seropositivity was observed in 78.6% of mothers and 8.9% of children before vaccination. After vaccination, seropositivity rates of 81.9% and 83.2%, seroconversion rates of 84.8% and 85.8% and rates of a four-fold increase over the pre-vaccination titre of 77.6% and 81.8% were observed in the 17D-213/77 and 17DD subgroups, respectively. There was no association with maternal immunity. Among children aged 12 months or older, the seroconversion rates of 69% were associated with concomitant vaccination against measles, mumps and rubella. The data were not conclusive regarding the interference of maternal immunity in the immune response to the YF vaccine, but they suggest interference from other vaccines. The failures in seroconversion after vaccination support the recommendation of a booster dose in children within 10 years of the first dose.