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Several technological approaches have been used to develop vaccines against COVID-19, including those based on inactivated viruses, viral vectors, and mRNA. This study aimed to monitor the maintenance of anti-SARS-CoV-2 antibodies in individuals from Brazil according to the primary vaccination regimen, as follows: BNT162b2 (group 1; 22) and ChAdOx1 (group 2; 18). Everyone received BNT162b2 in the first booster while in the second booster CoronaVac, Ad26.COV2.S, or BNT162b2. Blood samples were collected from 2021 to 2023 to analyze specific RBD (ELISA) and neutralizing antibodies (PRNT50). We observed a progressive increase in anti-RBD and neutralizing antibodies in each subsequent dose, remaining at high titers until the end of follow-up. Group 1 had higher anti-RBD antibody titers than group 2 after beginning the primary regimen, with significant differences after the 2nd and 3rd doses. Group 2 showed a more expressive increase after the first booster with BNT162B2 (heterologous booster). Group 2 also presented high levels of neutralizing antibodies against the Gamma and Delta variants until five months after the second booster. In conclusion, the circulating levels of anti-RBD and neutralizing antibodies against the two variants of SARS-CoV-2 were durable even five months after the 4th dose, suggesting that periodic booster vaccinations (homologous or heterologous) induced long-lasting immunity.
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Infecciones por Arbovirus , Enfermedades Transmisibles Emergentes , Enfermedades Transmitidas por Vectores , Enfermedades Transmisibles Emergentes/epidemiología , Humanos , Infecciones por Arbovirus/epidemiología , Infecciones por Arbovirus/transmisión , Enfermedades Transmitidas por Vectores/epidemiología , Américas/epidemiología , Animales , ArbovirusRESUMEN
Monkeypox virus (MPXV), belonging to the Poxviridae family and Orthopoxvirus genus, is closely related to the smallpox virus. Initial prodromal symptoms typically include headache, fever, and lymphadenopathy. This review aims to detail various ocular manifestations and immune evasion associated with the monkeypox viral infection and its complications, making it appropriate as a narrative review. Common external ocular manifestations of MPXV typically involve a generalized pustular rash, keratitis, discharges, and dried secretions related to conjunctival pustules, photophobia, and lacrimation. Orthopoxviruses can evade host immune responses by secreting proteins that antagonize the functions of host IFNγ, CC and CXC chemokines, IL-1ß, and the complement system. One of the most important transcription factors downstream of pattern recognition receptors binding is IRF3, which controls the expression of the crucial antiviral molecules IFNα and IFNß. We strongly recommend that ophthalmologists include MPXV as part of their differential diagnosis when they encounter similar cases presenting with ophthalmic manifestations such as conjunctivitis, blepharitis, or corneal lesions. Furthermore, because non-vaccinated individuals are more likely to exhibit these symptoms, it is recommended that healthcare administrators prioritize smallpox vaccination for at-risk groups, including very young children, pregnant women, older adults, and immunocompromised individuals, especially those in close contact with MPXV cases.
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Enfermedades de la Córnea , Monkeypox virus , Niño , Humanos , Femenino , Embarazo , Preescolar , Anciano , Evasión Inmune , Vacunación , PárpadosRESUMEN
Between 2016 and 2018, Brazil experienced the largest sylvatic epidemic of yellow fever virus (YFV). Despite to the magnitude and rapid spread of the epidemic, little is known about YFV dispersion. The study evaluated whether the squirrel monkey is a good model for yellow fever (YF) studies. Methods: Ten animals were infected with 1 × 106 PFU/mL of YFV, with one negative control. Blood samples were collected daily during the first 7 days and at 10, 20 and 30 days post infection (dpi) for detection of viral load and cytokines by RT-qPCR; measurements of AST, ALT, urea and creatinine were taken; IgM/IgG antibodies were detected by ELISA, and hemagglutination inhibition and neutralization tests were performed. The animals exhibited fever, flushed appearance, vomiting and petechiae, and one animal died. Viremia was detected between 1 and 10 dpi, and IgM/IgG antibodies appeared between 4 and 30 dpi. The levels of AST, ALT and urea increased. The immune responses were characterized by expression of S100 and CD11b cells; endothelial markers (VCAM-1, ICAM-1 and VLA-4), cell death and stress (Lysozyme and iNOS); and pro-inflammatory cytokines (IL-8, TNF-α, and IFN-γ) and anti-inflammatory cytokines (IL-10 and TGF-ß). The squirrel monkeys showed changes similar to those described in humans with YF, and are a good experimental model for the study of YF.
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Fiebre Amarilla , Humanos , Animales , Fiebre Amarilla/epidemiología , Saimiri , Virus de la Fiebre Amarilla , Citocinas , Inmunoglobulina M , Inmunoglobulina GRESUMEN
Non-human primates contribute to the spread of yellow fever virus (YFV) and the establishment of transmission cycles in endemic areas, such as Brazil. This study aims to investigate virological, histopathological and immunohistochemical findings in livers of squirrel monkeys (Saimiri spp.) infected with the YFV. Viremia occurred 1-30 days post infection (dpi) and the virus showed a predilection for the middle zone (Z2). The livers were jaundiced with subcapsular and hemorrhagic multifocal petechiae. Apoptosis, lytic and coagulative necrosis, steatosis and cellular edema were also observed. The immune response was characterized by the expression of S100, CD11b, CD57, CD4 and CD20; endothelial markers; stress and cell death; pro and anti-inflammatory cytokines, as well as Treg (IL-35) and IL-17 throughout the experimental period. Lesions during the severe phase of the disease were associated with excessive production of apoptotic pro-inflammatory cytokines, such as IFN-γ and TNF-α, released by inflammatory response cells (CD4+ and CD8+ T lymphocytes) and associated with high expression of molecules of adhesion in the inflammatory foci observed in Z2. Immunostaining of the local endothelium in vascular cells and the bile duct was intense, suggesting a fundamental role in liver damage and in the pathogenesis of the disease.
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Fiebre Amarilla , Animales , Saimiri , Virus de la Fiebre Amarilla , Hígado , CitocinasRESUMEN
Understanding the interaction between viruses and ecosystems in areas with or without anthropic interference can contribute to the organization of public health services, as well as prevention and disease control. An arbovirus survey was conducted at Caxiuanã National Forest, Pará, Brazil, where 632 local residents, 338 vertebrates and 15,774 pools of hematophagous arthropods were investigated. Neutralization antibodies of the Venezuelan Equine Encephalitis virus, subtype IIIA, Mucambo virus (MUCV) were detected in 57.3% and 61.5% of humans and wild vertebrates, respectively; in addition, genomic fragments of MUCV were detected in pool of Uranotaenia (Ura.) geometrica. The obtained data suggest an enzootic circulation of MUCV in the area. Understanding the circulation of endemic and neglected arboviruses, such as MUCV, represents an important health problem for the local residents and for the people living in the nearby urban centers.
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Alphavirus , Arbovirus , Culicidae , Virus de la Encefalitis Equina Venezolana , Animales , Humanos , Virus de la Encefalitis Equina Venezolana/genética , Brasil/epidemiología , Ecosistema , VertebradosRESUMEN
The COVID-19 pandemic is the biggest public health threat facing the world today. Multiple vaccines have been approved; however, the emergence of viral variants such as the recent Omicron raises the possibility of booster doses to achieve adequate protection. In Brazil, the CoronaVac (Sinovac, Beijing, China) vaccine was used; however, it is important to assess the immune response to this vaccine over time. This study aimed to monitor the anti-SARS-CoV-2 antibody responses in those immunized with CoronaVac and SARS-CoV-2 infected individuals. Samples were collected between August 2020 and August 2021. Within the vaccinated cohort, some individuals had a history of infection by SARS-CoV-2 prior to immunization, while others did not. We analyzed RBD-specific and neutralizing-antibodies. Anti-RBD antibodies were detected in both cohorts, with a peak between 45-90 days post infection or vaccination, followed by a steady decline over time. In those with a previous history of COVID-19, a higher, longer, more persistent response was observed. This trend was mirrored in the neutralization assays, where infection, followed by immunization, resulted in higher, longer lasting responses which were conditioned on the presence of levels of RBD antibodies right before the vaccination. This supports the necessity of booster doses of CoronaVac in due course to prevent serious disease.
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BACKGROUND: An outbreak of febrile illness was reported from January to February 2018 in the Expedito Ribeiro Settlement, ââSanta Bárbara do Pará municipality, Pará State, Brazil. OBJECTIVE: This study aimed to investigate the pathogenic agent responsible for the outbreak and the circulation of arboviruses in the region. STUDY DESIGN: We analyzed 94 individuals through laboratory tests for arboviruses. Forty out of 94 individuals were asymptomatic but were living with or near febrile cases, and 55 participants were symptomatic. RESULTS: Our results showed that 51.1% of the investigated individuals were positive for arboviruses (Oropouche, Mayaro, and Chikungunya), of which 77.8% were symptomatic. We detected 93.7% of positive cases for Oropouche infection, 2.1% for Mayaro fever, and 4.2% were positive for both Oropouche and Chikungunya infection. CONCLUSION: Oropouche virus was mainly responsible for the outbreak; however, we also detected a few Chikungunya and Mayaro fever cases. Serologic assays showed evidence of arboviruses circulation of different genera in the area.
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Infecciones por Arbovirus , Arbovirus , Infecciones por Bunyaviridae , Fiebre Chikungunya , Infecciones por Arbovirus/epidemiología , Brasil/epidemiología , Infecciones por Bunyaviridae/epidemiología , Fiebre Chikungunya/epidemiología , Brotes de Enfermedades , HumanosRESUMEN
Reporter virus neutralization test (RVNT) has been used as an alternative to the more laborious and time-demanding conventional PRNT assay for both DENV and ZIKV. However, few studies have investigated how these techniques would perform in epidemic areas with the circulation of multiple flavivirus. Here, we evaluate the performance of ZIKV and DENV Rluc RVNT and ZIKV mCh RVNT assays in comparison to the conventional PRNT assay against patient sera collected before and during ZIKV outbreak in Brazil. These samples were categorized into groups based on (1) acute and convalescent samples according to the time of disease, and (2) laboratorial diagnostic results (DENV and ZIKV RT-PCR and IgM-capture ELISA). Our results showed that DENV Rluc assay presented 100% and 78.3% sensitivity and specificity, respectively, with 93.3% accuracy, a similar performance to the traditional PRNT. ZIKV RVNT90, on the other hand, showed much better ZIKV antibody detection performance (around nine-fold higher) when compared to PRNT, with 88% clinical sensitivity. Specificity values were on average 76.8%. Even with these results, however, ZIKV RVNT90 alone was not able to reach a final diagnostic conclusion for secondary infection in human samples due to flavivirus cross reaction. As such, in regions where the flavivirus differential diagnosis represents a challenge, we suggest the establishment of a RVNT panel including other flaviviruses circulating in the region, associated with the other serological techniques such as IgM ELISA and the investigation of seroconversion, in order to help define an accurate diagnostic conclusion using serology.
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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.
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Landscape change is one of the foremost drivers of the emergence of infectious diseases. Exploring demographic, household and environmental conditions under which infectious diseases occur may inform strategies to prevent disease emergence in human populations. We collected blood samples from 523 humans and explore factors for arbovirus emergence in Bahia, Brazil. The overall arbovirus seroprevalence was 65.2%, with the genus Flavivirus most prevalent (64.4%). Based on monotypic reactions, the population had contact with five arbovirus: Dengue 3, Ilheus, Oropouche, Caraparu and Eastern equine encephalitis virus. To our knowledge, this is the first study reporting exposure to Oropouche, Caraparu and Eastern equine encephalitis virus in human populations in Bahia, Northeast of Brazil. The best model fit demonstrated that household and environmental variables were more predictive of the risk of arbovirus exposure than demographic variables. The presence of forest and free-living monkeys in the areas close to the communities had a protective effect for the human population (i.e. lower seroprevalence). The dilution effect is considered as one explanation for this finding. These results highlight the important ecological role of wildlife-friendly agriculture.
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Arbovirus/aislamiento & purificación , Microbiología Ambiental , Población Rural , Adolescente , Adulto , Anciano , Anticuerpos Antivirales/sangre , Brasil/epidemiología , Niño , Composición Familiar , Femenino , Vivienda , Humanos , Masculino , Factores de Riesgo , Estudios SeroepidemiológicosRESUMEN
Zika and Dengue viruses present considerable immunological cross-reactivity, resulting in a troublesome serodiagnosis due to occurrence of false positive results. Due to Brazil's wide variety of circulating flaviviruses we aimed to access the use of in house serological tests adapted by National Reference Laboratory for Arboviruses in Brazil and evaluate commercial tests available. We evaluated in house IgM ELISAs for the individual detection of anti-ZIKV, -DENV, and -YFV IgM, against a panel of samples positive for dengue, zika, yellow fever, Rocio, Ilheus, Saint Louis encephalitis, West Nile and chikungunya. We also evaluated two commercial kits for dengue and zika IgM detection recommended by the Brazilian Ministry of Health in 2015. The sensitivity and specificity for the in house ZIKV IgM ELISA was 60.0 % and 88.6 % and for the in house DENV IgM ELISA was 100 % and 82.2 %, respectively. The in house YFV IgM ELISA presented 100 % for both sensitivity and specificity. The Novagnost Zika Virus IgM test presented a sensitivity of 47.3 % and specificity of 85.3 % and the Serion ELISA classic Dengue Virus IgM, 92.8 % and 58.9 %, respectively. Overall, both in house ELISAs for ZIKV and DENV adapted and evaluated here, presented better performances than the commercial kits tested.
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Virus del Dengue , Dengue , Flavivirus , Infección por el Virus Zika , Virus Zika , Anticuerpos Antivirales , Dengue/diagnóstico , Ensayo de Inmunoadsorción Enzimática , Humanos , Inmunoglobulina M , Laboratorios , Sensibilidad y Especificidad , Infección por el Virus Zika/diagnósticoRESUMEN
The Asian lineage of Zika virus (ZIKV) is responsible for the recent epidemics in the Americas and severe disease, whereas the African lineage of ZIKV has not been reported to cause epidemics or severe disease. We constructed a cDNA infectious clone (IC) of an African ZIKV strain, which, together with our previously developed Asian ZIKV strain IC, allowed us to engineer chimeric viruses by swapping the structural and non-structural genes between the two lineages. Recombinant parental and chimeric viruses were analyzed in A129 and newborn CD1 mouse models. In the A129 mice, the African strain developed higher viremia, organ viral loading, and mortality rate. In CD1 mice, the African strain exhibited a higher neurovirulence than the Asian strain. A chimeric virus containing the structural genes from the African strain is more virulent than the Asian strain, whereas a chimeric virus containing the non-structural genes from the African strain exhibited a virulence comparable to the Asian strain. These results suggest that (i) African strain is more virulent than Asian strain and (ii) viral structural genes primarily determine the virulence difference between the two lineages in mouse models. Other factors may contribute to the discrepancy between the mouse and epidemic results.
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Genes Virales , Variación Genética , Virulencia/genética , Infección por el Virus Zika/patología , Virus Zika , África , Américas/epidemiología , Animales , Asia , Chlorocebus aethiops , Modelos Animales de Enfermedad , Humanos , Ratones , Células Vero , Virus Zika/genética , Virus Zika/aislamiento & purificación , Virus Zika/patogenicidadRESUMEN
Zika virus (ZIKV) infection during pregnancy causes congenital abnormalities, including microcephaly. However, rates vary widely, and the contributing risk factors remain unclear. We examined the serum antibody response to ZIKV and other flaviviruses in Brazilian women giving birth during the 2015-2016 outbreak. Infected pregnancies with intermediate or higher ZIKV antibody enhancement titers were at increased risk to give birth to microcephalic infants compared with those with lower titers (P < 0.0001). Similarly, analysis of ZIKV-infected pregnant macaques revealed that fetal brain damage was more frequent in mothers with higher enhancement titers. Thus, features of the maternal antibodies are associated with and may contribute to the genesis of ZIKV-associated microcephaly.
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Anticuerpos Antivirales/inmunología , Intercambio Materno-Fetal/inmunología , Microcefalia/inmunología , Complicaciones Infecciosas del Embarazo/inmunología , Infección por el Virus Zika/inmunología , Virus Zika/inmunología , Animales , Encéfalo/embriología , Encéfalo/inmunología , Encéfalo/patología , Femenino , Feto/embriología , Feto/inmunología , Feto/patología , Humanos , Células K562 , Macaca mulatta , Macaca nemestrina , Microcefalia/patología , Embarazo , Complicaciones Infecciosas del Embarazo/patología , Infección por el Virus Zika/patologíaRESUMEN
INTRODUCTION: The recent Zika virus(ZIKV) epidemic in Brazil was characterized by a range of different clinical presentations, particularly microcephaly, Guillain-Barré syndrome, and death. In this context, we determined the causal relationship between fatal microcephaly cases and ZIKV infection. METHODS: Twelve fatal cases of neonates, whose mothers were infected with ZIKV during pregnancy, were examined; cases included nine neonatal deaths due to microcephaly, one miscarriage, and two stillbirths. Tissue samples were obtained from all cases at necropsy and were submitted for virological investigation (RT-qPCR and virus isolation) and/or histopathology (hematoxylin and eosin staining) and immunohistochemical assay for the detection of ZIKV antigens. RESULTS: ZIKV antigens and/or ZIKV RNA were detected in tissue samples of all 12 cases examined. ZIKV was recovered in one case. Results of the virological and immunohistochemical analyses, as well as the anatomic abnormalities and histopathologic changes observed at necropsy on the 12 fatal cases, are presented. CONCLUSIONS: Data from these 12 cases provide strong evidence of the causal relationship between ZIKV and congenital disease in fetuses of women who were infected with the virus during pregnancy.
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Zika virus (ZIKV) infection of the mother during pregnancy causes devastating Zika congenital syndrome in the offspring. A ZIKV vaccine with optimal safety and immunogenicity for use in pregnant women is critically needed. Toward this goal, we have developed a single-dose live-attenuated vaccine candidate that infects cells with controlled, limited infection rounds. The vaccine contains a 9-amino-acid deletion in the viral capsid protein and replicates to titers of > 106 focus-forming units (FFU)/mL in cells expressing the full-length capsid protein. Immunization of A129 mice with one dose (105 FFU) did not produce viremia, but elicited protective immunity that completely prevented viremia, morbidity, and mortality after challenge with an epidemic ZIKV strain (106 PFU). A single-dose vaccination also fully prevented infection of pregnant mice and maternal-to-fetal transmission. Intracranial injection of the vaccine (104 FFU) to 1-day-old mice did not cause any disease or death, underscoring the safety of this vaccine candidate.
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Proteínas de la Cápside/inmunología , Transmisión Vertical de Enfermedad Infecciosa/prevención & control , Vacunas Virales/inmunología , Infección por el Virus Zika/prevención & control , Virus Zika/inmunología , Células A549 , Animales , Proteínas de la Cápside/genética , Línea Celular , Chlorocebus aethiops , Cricetinae , Femenino , Humanos , Masculino , Ratones , Ratones Endogámicos , Ratones Noqueados , Embarazo , Vacunas Atenuadas/administración & dosificación , Vacunas Atenuadas/inmunología , Células Vero , Vacunas Virales/administración & dosificación , Virus Zika/genética , Infección por el Virus Zika/virologíaRESUMEN
Zika virus (ZIKV) is a single-stranded positive-sense RNA flavivirus that possesses a genome approximately 10.7 Kb in length. Although pro-inflammatory and anti-inflammatory cytokines and apoptotic markers belonging to the extrinsic and intrinsic pathways are suggested to be involved in fatal cases of ZIKV-induced microcephaly, their exact roles and associations are unclear. To address this, brain tissue samples were collected from 10 individuals, five of whom were diagnosed as ZIKV positive with microcephaly and a further five were flavivirus-negative controls that died because of other causes. Examination of material from the fatal cases of microcephaly revealed lesions in the cerebral cortex, edema, vascular proliferation, neuronal necrosis, gliosis, neuronophagy, calcifications, apoptosis, and neuron loss. The expression of various apoptosis markers in the neural parenchyma, including FasL, FAS, BAX, BCL2, and caspase 3 differed between ZIKV-positive cases and controls. Further investigation of type 1 and 2 helper T-cell cytokines confirmed a greater anti-inflammatory response in fatal ZIKV-associated microcephaly cases. Finally, an analysis of the linear correlation between tumor necrosis factor-α, IL-1ß, IL-4, IL-10, transforming growth factor-ß, and IL-33 expression and various apoptotic markers suggested that the immune response may be associated with the apoptotic phenomenon observed in ZIKV-induced microcephaly.
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Apoptosis , Microcefalia/inmunología , Microcefalia/patología , Neuronas/inmunología , Tejido Parenquimatoso/inmunología , Infección por el Virus Zika/complicaciones , Virus Zika/patogenicidad , Citocinas/metabolismo , Femenino , Humanos , Recién Nacido , Masculino , Microcefalia/virología , Neuronas/patología , Neuronas/virología , Tejido Parenquimatoso/patología , Tejido Parenquimatoso/virología , Embarazo , Infección por el Virus Zika/virologíaRESUMEN
Zika virus (ZIKV) has recently caused a pandemic disease, and many cases of ZIKV infection in pregnant women resulted in abortion, stillbirth, deaths and congenital defects including microcephaly, which now has been proposed as ZIKV congenital syndrome. This study aimed to investigate the in situ immune response profile and mechanisms of neuronal cell damage in fatal Zika microcephaly cases. Brain tissue samples were collected from 15 cases, including 10 microcephalic ZIKV-positive neonates with fatal outcome and five neonatal control flavivirus-negative neonates that died due to other causes, but with preserved central nervous system (CNS) architecture. In microcephaly cases, the histopathological features of the tissue samples were characterized in three CNS areas (meninges, perivascular space, and parenchyma). The changes found were mainly calcification, necrosis, neuronophagy, gliosis, microglial nodules, and inflammatory infiltration of mononuclear cells. The in situ immune response against ZIKV in the CNS of newborns is complex. Despite the predominant expression of Th2 cytokines, other cytokines such as Th1, Th17, Treg, Th9, and Th22 are involved to a lesser extent, but are still likely to participate in the immunopathogenic mechanisms of neural disease in fatal cases of microcephaly caused by ZIKV.