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1.
Proc Natl Acad Sci U S A ; 121(28): e2302924121, 2024 Jul 09.
Artigo em Inglês | MEDLINE | ID: mdl-38950368

RESUMO

The human colonization of the Canary Islands represents the sole known expansion of Berber communities into the Atlantic Ocean and is an example of marine dispersal carried out by an African population. While this island colonization shows similarities to the populating of other islands across the world, several questions still need to be answered before this case can be included in wider debates regarding patterns of initial colonization and human settlement, human-environment interactions, and the emergence of island identities. Specifically, the chronology of the first human settlement of the Canary Islands remains disputed due to differing estimates of the timing of its first colonization. This absence of a consensus has resulted in divergent hypotheses regarding the motivations that led early settlers to migrate to the islands, e.g., ecological or demographic. Distinct motivations would imply differences in the strategies and dynamics of colonization; thus, identifying them is crucial to understanding how these populations developed in such environments. In response, the current study assembles a comprehensive dataset of the most reliable radiocarbon dates, which were used for building Bayesian models of colonization. The findings suggest that i) the Romans most likely discovered the islands around the 1st century BCE; ii) Berber groups from western North Africa first set foot on one of the islands closest to the African mainland sometime between the 1st and 3rd centuries CE; iii) Roman and Berber societies did not live simultaneously in the Canary Islands; and iv) the Berber people rapidly spread throughout the archipelago.


Assuntos
Migração Humana , Humanos , Espanha , Migração Humana/história , Teorema de Bayes , História Antiga , Datação Radiométrica
2.
J Exp Med ; 221(5)2024 May 06.
Artigo em Inglês | MEDLINE | ID: mdl-38557723

RESUMO

CD4+ T cells are vital for host defense and immune regulation. However, the fundamental role of CD4 itself remains enigmatic. We report seven patients aged 5-61 years from five families of four ancestries with autosomal recessive CD4 deficiency and a range of infections, including recalcitrant warts and Whipple's disease. All patients are homozygous for rare deleterious CD4 variants impacting expression of the canonical CD4 isoform. A shorter expressed isoform that interacts with LCK, but not HLA class II, is affected by only one variant. All patients lack CD4+ T cells and have increased numbers of TCRαß+CD4-CD8- T cells, which phenotypically and transcriptionally resemble conventional Th cells. Finally, patient CD4-CD8- αß T cells exhibit intact responses to HLA class II-restricted antigens and promote B cell differentiation in vitro. Thus, compensatory development of Th cells enables patients with inherited CD4 deficiency to acquire effective cellular and humoral immunity against an unexpectedly large range of pathogens. Nevertheless, CD4 is indispensable for protective immunity against at least human papillomaviruses and Trophyrema whipplei.


Assuntos
Linfócitos T CD4-Positivos , Linfócitos T Auxiliares-Indutores , Humanos , Linfócitos T CD8-Positivos , Ativação Linfocitária , Antígenos HLA , Isoformas de Proteínas/metabolismo
4.
Anthropol Anz ; 81(1): 79-107, 2024 Jan 25.
Artigo em Inglês | MEDLINE | ID: mdl-37548019

RESUMO

Skeletal remains of two prehispanic male adult individuals (antiquity ≈ 550 BP) recovered from a burial cave located in Montaña Blanca (Las Cañadas del Teide) at an altitude of 2450 m above sea level, in the highlands of Tenerife (Canary Islands) showed some unusual features. Femora and tibiae of both individuals showed increased bone density, with irregular thickening of the midshaft diaphyses. One individual showed a cystic lesion in the distal third of the left femoral diaphysis, surrounded by a subtle sclerotic reaction of the spongiosa and a thin cortex that was partially fractured. Periosteal thickening was present, but not around the cystic lesion. A thoracic vertebra with rachischisis was also recovered. The bone density of vertebrae and iliac bones were normal, and one recovered jaw was also normal. The tibiae of one individual showed an abnormal location of the foramen nutritium. Hypoplasia of the lesser trochanter and an abnormally thin left femoral neck were also observed. It is possible that both individuals were affected by diaphyseal dysplasia (possibly Camurati Engelmann or Ribbing disease). One of them also showed a lesion compatible with a unicameral bone cyst. The alternative possibility of a Klippel-Trenaunay-Weber disease, with a bone aneurysmal cyst, also exists.


Assuntos
Cistos Ósseos , Síndrome de Camurati-Engelmann , Adulto , Humanos , Masculino , Espanha , Sepultamento , Canadá
5.
J Fungi (Basel) ; 9(10)2023 Oct 08.
Artigo em Inglês | MEDLINE | ID: mdl-37888252

RESUMO

(1) Background: The entomopathogenic fungus Metarhizium anisopliae sensu lato forms a species complex, comprising a tight cluster made up of four species, namely M. anisopliae sensu stricto, M. pinghaense, M. robertsii and M. brunneum. Unambiguous species delineation within this "PARB clade" that enables both the taxonomic assignment of new isolates and the identification of potentially new species is highly solicited. (2) Methods: Species-discriminating primer pairs targeting the ribosomal intergenic spacer (rIGS) sequence were designed and a diagnostic PCR protocol established. A partial rIGS sequence, referred to as rIGS-ID800, was introduced as a molecular taxonomic marker for PARB species delineation. (3) Results: PARB species from a validation strain set not implied in primer design were clearly discriminated using the diagnostic PCR protocol developed. Using rIGS-ID800 as a single sequence taxonomic marker gave rise to a higher resolution and statistically better supported delineation of PARB clade species. (4) Conclusions: Reliable species discrimination within the Metarhizium PARB clade is possible through both sequencing-independent diagnostic PCR and sequencing-dependent single marker comparison, both based on the rIGS marker.

6.
Front Cell Dev Biol ; 11: 1209589, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37842096

RESUMO

A powerful method to qualitatively analyze a 2D system is the use of nullclines, curves which separate regions of the plane where the sign of the time derivatives is constant, with their intersections corresponding to steady states. As a quick way to sketch the phase portrait of the system, they can be sufficient to understand the qualitative dynamics at play without integrating the differential equations. While it cannot be extended straightforwardly for dimensions higher than 2, sometimes the phase portrait can still be projected onto a 2-dimensional subspace, with some curves becoming pseudo-nullclines. In this work, we study cell signaling models of dimension higher than 2 with behaviors such as oscillations and bistability. Pseudo-nullclines are defined and used to qualitatively analyze the dynamics involved. Our method applies when a system can be decomposed into 2 modules, mutually coupled through 2 scalar variables. At the same time, it helps track bifurcations in a quick and efficient manner, key for understanding the different behaviors. Our results are both consistent with the expected dynamics, and also lead to new responses like excitability. Further work could test the method for other regions of parameter space and determine how to extend it to three-module systems.

7.
Nat Commun ; 14(1): 4641, 2023 08 15.
Artigo em Inglês | MEDLINE | ID: mdl-37582830

RESUMO

The indigenous population of the Canary Islands, which colonized the archipelago around the 3rd century CE, provides both a window into the past of North Africa and a unique model to explore the effects of insularity. We generate genome-wide data from 40 individuals from the seven islands, dated between the 3rd-16rd centuries CE. Along with components already present in Moroccan Neolithic populations, the Canarian natives show signatures related to Bronze Age expansions in Eurasia and trans-Saharan migrations. The lack of gene flow between islands and constant or decreasing effective population sizes suggest that populations were isolated. While some island populations maintained relatively high genetic diversity, with the only detected bottleneck coinciding with the colonization time, other islands with fewer natural resources show the effects of insularity and isolation. Finally, consistent genetic differentiation between eastern and western islands points to a more complex colonization process than previously thought.


Assuntos
Deriva Genética , Genômica , Humanos , Espanha , África do Norte , Povos Indígenas , Ilhas , Variação Genética , Genética Populacional
8.
Diagnostics (Basel) ; 13(8)2023 Apr 10.
Artigo em Inglês | MEDLINE | ID: mdl-37189486

RESUMO

Since the Bosniak cysts classification is highly reader-dependent, automated tools based on radiomics could help in the diagnosis of the lesion. This study is an initial step in the search for radiomic features that may be good classifiers of benign-malignant Bosniak cysts in machine learning models. A CCR phantom was used through five CT scanners. Registration was performed with ARIA software, while Quibim Precision was used for feature extraction. R software was used for the statistical analysis. Robust radiomic features based on repeatability and reproducibility criteria were chosen. Excellent correlation criteria between different radiologists during lesion segmentation were imposed. With the selected features, their classification ability in benignity-malignity terms was assessed. From the phantom study, 25.3% of the features were robust. For the study of inter-observer correlation (ICC) in the segmentation of cystic masses, 82 subjects were prospectively selected, finding 48.4% of the features as excellent regarding concordance. Comparing both datasets, 12 features were established as repeatable, reproducible, and useful for the classification of Bosniak cysts and could serve as initial candidates for the elaboration of a classification model. With those features, the Linear Discriminant Analysis model classified the Bosniak cysts in terms of benignity or malignancy with 88.2% accuracy.

9.
Sci Rep ; 13(1): 529, 2023 01 11.
Artigo em Inglês | MEDLINE | ID: mdl-36631477

RESUMO

In this article, we consider a double phosphorylation cycle, a ubiquitous signaling component, having the ability to display bistability, a behavior strongly related to the existence of positive feedback loops. If this component is connected to other signaling elements, it very likely undergoes some sort of protein-protein interaction. In several cases, these interactions result in a non-explicit negative feedback effect, leading to interlinked positive and negative feedbacks. This combination was studied in the literature as a way to generate relaxation-type oscillations. Here, we show that the two feedbacks together ensure two types of oscillations, the relaxation-type ones and a smoother type of oscillations functioning in a very narrow range of frequencies, in such a way that outside that range, the amplitude of the oscillations is severely compromised. Even more, we show that the two feedbacks are essential for both oscillatory types to emerge, and it is their hierarchy what determines the type of oscillation at work. We used bifurcation analyses and amplitude vs. frequency curves to characterize and classify the oscillations. We also applied the same ideas to another simple model, with the goal of generalizing what we learned from signaling models. The results obtained display the wealth of oscillatory dynamics that exists in a system with a bistable module nested within a negative feedback loop, showing how to transition between different types of oscillations and other dynamical behaviors such as excitability. Our work provides a framework for the study of other oscillatory systems based on bistable modules, from simple two-component models to more complex examples like the MAPK cascade and experimental cases like cell cycle oscillators.


Assuntos
Retroalimentação Fisiológica , Transdução de Sinais , Retroalimentação , Sistema de Sinalização das MAP Quinases , Fosforilação , Modelos Biológicos
10.
Anthropol Anz ; 80(2): 205-223, 2023 Mar 16.
Artigo em Inglês | MEDLINE | ID: mdl-36458989

RESUMO

We describe diffuse microporotic lesions observed in most of the scattered skeletal remains belonging to a ≈ 6 months-old female (genetic sexing) prehispanic (antiquity ≈ 600 years BP) individual recovered from a small recess of a basaltic burial cave in the highlands (2300 m above sea level) of Tenerife. Although sphenoid wings were lacking, microporotic lesions were present in several bones, especially in the hard palate, basilar part of the occipital bone, outer aspect of the maxilla, and proximal half of the right humerus, accompanied by a subtle periosteal reaction. Although non-specific, bone lesions may be compatible with scurvy, possibly in the context of malnutrition, that probably also affected the mother, given the young age of the infant and her dependence on maternal feeding. Pathophysiological connections among iron deficiency, vitamin C deficiency and vitamin D deficiency are discussed. Both observational reports on paleopathological cases of diffuse microporotic lesions as well as experimental studies devoted to discern the relative and combined effects of hypoxia-mediated bone marrow expansion, protein-calorie malnutrition, ascorbate, vitamin D or iron deficiency on such lesions are needed.


Assuntos
Escorbuto , Humanos , Lactente , Feminino , Escorbuto/patologia , Osso e Ossos , Ácido Ascórbico , Vitamina D , Vitaminas
11.
J Clin Sleep Med ; 19(3): 595-603, 2023 03 01.
Artigo em Inglês | MEDLINE | ID: mdl-36546360

RESUMO

Detailed primary data collected from sleep studies should lead to specific and clear reports with evidence-based clinical recommendations that, when introduced by sleep medicine specialists, create a window of opportunity to support our non-sleep medicine referring teams and to engage patients and caregivers in their care as recipients of the reports. This is how sleep study reporting differs from other test reports; currently, there is wide variation in how the data collected are presented and summarized. The goal of this document is to offer recommendations for structured reporting of sleep studies. We offer a practical, complete, and relevant document and a structure that can be implemented across sleep centers nationwide and does not burden the interpreter. We anticipate some readers will opine that some of the content is beyond the scope of what the interpreter physician needs to include, while others will propose missing data that they feel should have been included. We feel that the flexibility of the proposal accommodates for this and allows for a "first step" toward standardization of physician reporting of sleep studies. High-quality structured reporting of sleep studies is becoming ever more important for patient care, benefiting patients, caregivers, clinicians, durable medical equipment companies, and payers. CITATION: Lastra AC, Ingram D, Park J, et al. Moving toward standardization: physician reporting of sleep studies. J Clin Sleep Med. 2023;19(3):595-603.


Assuntos
Equipamentos Médicos Duráveis , Humanos , Polissonografia , Padrões de Referência
12.
Cureus ; 15(12): e50402, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-38213354

RESUMO

Lymphangiomas are benign deformities of the lymphatic system that are most common in pediatric populations and are usually found in the neck, axilla, chest wall, cervicofacial, and pelvic regions, as they are areas with more lymphatic activity. Herein, we report the case of a 43-year-old African-American male who presented with bilateral inguinal lymphangiomas, the first documented incidence of its kind. This patient presented with several months of bilateral swellings in his groin area, accompanied by increased tenderness and discomfort. A physical exam revealed that the left groin swelling was larger than the right groin swelling and that the left lymph node was about < 2 cm in size. Bilaterally, there was no tenderness of the lymph nodes in the area and no skin changes, ulceration, induration, discharge, or bleeding from the site. The diagnostic assessment included ultrasound, a left inguinal lymphadenectomy, and a frozen section biopsy to provide a definitive diagnosis. The pathology report described the lesion as a benign lymphangioma and was negative for lymphoproliferative lesions.

13.
Medicina (B Aires) ; 82(6): 927-933, 2022.
Artigo em Espanhol | MEDLINE | ID: mdl-36571532

RESUMO

The systematic registry of contacts with the objective of identifying and treating those with tuberculosis infection is one of the pillars established by the WHO in the end Tuberculosis Strategy. The risk of tuberculosis infection in school contacts, although lower than in households, is significant. However, compliance with preventive treatment is low and several points are open to discussion, such as the cutoff of the tuberculin test to be used, the usefulness of starting a chemoprophylactic treatment in the absence of confirmed infection or carrying out studies in contacts of non-bacilliferous index cases. This paper addresses these issues and proposes, with updated evidence, a screening modality for contacts in higher education institutions. This screening proposes to identify those infected using the cut-off point of 5 mm in the tuberculin test, offering preventive treatment and active follow-up only to those with a positive test.


El catastro sistemático de contactos con el objetivo de identificar y tratar a aquellos con infección tuberculosa es uno de los pilares establecidos por la OMS en su Estrategia de Fin a la Tuberculosis. El riesgo de infección tuberculosa en contactos escolares, aunque menor que en los domiciliarios, es significativo. Sin embargo, es bajo el cumplimiento del tratamiento preventivo y varios puntos se prestan a discusión, como ser el corte de la prueba tuberculínica a utilizar, el beneficio de iniciar un tratamiento quimioprofiláctico en ausencia de infección demostrada o de realizar estudios en contactos de casos índice no bacilíferos. Este escrito aborda dichos temas y propone, con evidencia actualizada, una modalidad de estudio para contactos en instituciones de enseñanza secundaria. Dicho catastro propone identificar a los infectados utilizando el punto de corte de 5 mm en la prueba de tuberculina, ofreciendo tratamiento preventivo y seguimiento activo solamente a aquellos con una prueba positiva.


Assuntos
Tuberculose Latente , Tuberculose , Humanos , Tuberculose/diagnóstico , Tuberculose/epidemiologia , Tuberculose/prevenção & controle , Teste Tuberculínico , Tuberculose Latente/diagnóstico , Programas de Rastreamento , Instituições Acadêmicas
14.
Medicina (B.Aires) ; 82(6): 927-933, dic. 2022. graf
Artigo em Espanhol | LILACS-Express | LILACS | ID: biblio-1422088

RESUMO

Resumen El catastro sistemático de contactos con el objetivo de identificar y tratar a aquellos con infección tuberculosa es uno de los pilares establecidos por la OMS en su Estrategia de Fin a la Tuberculosis. El riesgo de infección tuberculosa en contactos escolares, aunque menor que en los domiciliarios, es significativo. Sin embargo, es bajo el cumplimiento del tratamiento preventivo y varios puntos se prestan a discusión, como ser el corte de la prueba tuberculínica a utilizar, el beneficio de iniciar un tratamiento quimioprofiláctico en ausencia de infección demostrada o de realizar estudios en contactos de casos índice no bacilíferos. Este escrito aborda dichos temas y propone, con evidencia actualizada, una modalidad de estudio para contactos en instituciones de enseñanza secundaria. Dicho catastro propone identificar a los infectados utilizando el punto de corte de 5 mm en la prueba de tuberculina, ofreciendo tratamiento preventivo y seguimiento activo solamente a aquellos con una prueba positiva.


Abstract The systematic registry of contacts with the objective of identifying and treating those with tuberculosis infection is one of the pillars established by the WHO in the end Tuberculosis Strategy. The risk of tuberculosis infection in school contacts, although lower than in households, is significant. However, compliance with preventive treatment is low and several points are open to discussion, such as the cutoff of the tuberculin test to be used, the usefulness of starting a chemoprophylactic treatment in the absence of confirmed infection or carrying out studies in contacts of non-bacilliferous index cases. This paper ad dresses these issues and proposes, with updated evidence, a screening modality for contacts in higher education institutions. This screening proposes to identify those infected using the cut-off point of 5 mm in the tuberculin test, offering preventive treatment and active follow-up only to those with a positive test.

15.
Pharmaceutics ; 14(11)2022 Oct 22.
Artigo em Inglês | MEDLINE | ID: mdl-36365077

RESUMO

The development of X-ray-absorbing scintillating nanoparticles is of high interest for solving the short penetration depth problem of visible and infrared light in photodynamic therapy (PDT). Thus, these nanoparticles are considered a promising treatment for several types of cancer. Herein, gadolinium oxide nanoparticles doped with europium ions (Gd2O3:Eu3+) were obtained by using polyvinyl alcohol as a capping agent. Hybrid silica nanoparticles decorated with europium-doped gadolinium oxide (SiO2-Gd2O3:Eu3+) were also prepared through the impregnation method. The synthesized nanoparticles were structurally characterized and tested to analyze their biocompatibility. X-ray diffraction, scanning electron microscopy, and transmission electron microscopy confirmed the high crystallinity and purity of the Gd2O3:Eu3+ particles and the homogeneous distribution of nanostructured rare earth oxides throughout the fumed silica matrix for SiO2-Gd2O3:Eu3+. Both nanoparticles displayed stable negative ζ-potentials. The photoluminescence properties of the materials were obtained using a Xe lamp as an excitation source, and they exhibited characteristic Eu3+ bands, including at 610 nm, which is the most intense transition band of this ion. Cytotoxicity studies on mouse glioblastoma GL261 cells indicated that these materials appear to be nontoxic from 10 to 500 µg·mL-1 and show a small reduction in viability in non-tumor cell lines. All these findings demonstrate their possible use as alternative materials in PDT.

16.
BMJ Case Rep ; 15(9)2022 Sep 28.
Artigo em Inglês | MEDLINE | ID: mdl-36171011

RESUMO

A woman in her 30s with medically intractable epilepsy and Lennox-Gastaut Syndrome on multiple antiseizure medications and with a deep brain stimulator presented to the epilepsy monitoring unit with increased seizure frequency. She was noted to have periods of apparent apnoea time linked to bursts of epileptiform activity on continuous video EEG monitoring. Once the clinical seizures were controlled, she was discharged to the sleep laboratory. She was noted to have obstructive and central sleep apnoea, which improved with the use of positive airway pressure. Central sleep apnoeas were time linked to electrographic seizures. Ictal central apnoea can easily be overlooked and is likely more common than currently recognised in patients with epilepsy. Ictal central apnoea may be a biomarker for sudden unexpected death in epilepsy.


Assuntos
Epilepsia Resistente a Medicamentos , Epilepsia , Apneia do Sono Tipo Central , Apneia , Morte Súbita , Epilepsia Resistente a Medicamentos/complicações , Epilepsia Resistente a Medicamentos/terapia , Eletroencefalografia , Epilepsia/complicações , Feminino , Humanos , Convulsões , Apneia do Sono Tipo Central/complicações , Apneia do Sono Tipo Central/diagnóstico
17.
Infect Dis (Lond) ; 54(11): 810-818, 2022 11.
Artigo em Inglês | MEDLINE | ID: mdl-35854671

RESUMO

BACKGROUND: COVID-19 may trigger an acute hyperinflammatory syndrome characterised by heightened levels of acute phase reactants and is associated with adverse outcomes among hospitalised individuals. The relationship between 48-hour changes in acute phase reactants and adverse outcomes is unclear. This study evaluated the relationship between change in four acute phase reactants (interleukin-6, procalcitonin, ferritin, and C-reactive protein), and the risk for in-hospital death and invasive mechanical ventilation. METHODS: A retrospective cohort among 2,523 adult patients hospitalised with COVID-19 pneumonia was conducted. Changes in IL-6, procalcitonin, ferritin, and CRP from admission to 48 h after admission were recorded. Delta was calculated using the difference in each acute phase reactant at admission and at 48-hours. Delta in acute phase reactants and the risk for in-hospital death and invasive mechanical ventilation was assessed using logistic regression models adjusting for demographics and comorbidities. RESULTS: Patients with both admission and 48-hour measurement for interleukin-6 (IL-6) (n = 541), procalcitonin (n = 828), ferritin (n = 1022), and C-reactive protein (CRP) (n = 1919) were included. Baseline characteristics were similar across all four populations. Increases in ferritin associated with a heightened risk of in-hospital death (OR 1.00032; 95%CI 1.00007- 1.00056; p < .001) and invasive mechanical ventilation (OR 1.00035; 95%CI 1.00014- 1.00055; p = .001). Therefore, for every 100 ng/mL increase in ferritin, the odds for in-hospital death and invasive mechanical ventilation increase by 3.2% and 3.5%, respectively. CONCLUSIONS: Delta in ferritin is associated with in-hospital death and invasive mechanical ventilation. Other acute phase reactants were not associated with these outcomes among COVID-19 inpatients.


Assuntos
COVID-19 , Adulto , Proteína C-Reativa , COVID-19/terapia , Ferritinas , Mortalidade Hospitalar , Humanos , Interleucina-6 , Pró-Calcitonina , Respiração Artificial , Estudos Retrospectivos , SARS-CoV-2
18.
N Engl J Med ; 386(25): 2377-2386, 2022 06 23.
Artigo em Inglês | MEDLINE | ID: mdl-35731653

RESUMO

BACKGROUND: Although human respiratory syncytial virus (RSV) is an important cause of illness and death in older adults, no RSV vaccine has been licensed. METHODS: In a phase 2a study, we randomly assigned healthy adults (18 to 50 years of age), in a 1:1 ratio, to receive a single intramuscular injection of either bivalent prefusion F (RSVpreF) vaccine or placebo. Approximately 28 days after injection, participants were inoculated intranasally with the RSV A Memphis 37b challenge virus and observed for 12 days. The per-protocol prespecified primary end points were the following: reverse-transcriptase-quantitative polymerase-chain-reaction (RT-qPCR)-confirmed detectable RSV infection on at least 2 consecutive days with at least one clinical symptom of any grade from two categories or at least one grade 2 symptom from any category, the total symptom score from day 1 to discharge, and the area under the curve (AUC) for the RSV viral load in nasal-wash samples measured by means of RT-qPCR from day 2 after challenge to discharge. In addition, we assessed immunogenicity and safety. RESULTS: After participants were inoculated with the challenge virus, vaccine efficacy of 86.7% (95% CI, 53.8 to 96.5) was observed for symptomatic RSV infection confirmed by any detectable viral RNA on at least 2 consecutive days. The median AUC for the RSV viral load (hours × log10 copies per milliliter) as measured by RT-qPCR assay was 0.0 (interquartile range, 0.0 to 19.0) in the vaccine group and 96.7 (interquartile range, 0.0 to 675.3) in the placebo group. The geometric mean factor increase from baseline in RSV A-neutralizing titers 28 days after injection was 20.5 (95% CI, 16.6 to 25.3) in the vaccine group and 1.1 (95% CI, 0.9 to 1.3) in the placebo group. More local injection-site pain was noted in the vaccine group than in the placebo group. No serious adverse events were observed in either group. CONCLUSIONS: RSVpreF vaccine was effective against symptomatic RSV infection and viral shedding. No evident safety concerns were identified. These findings provide support for further evaluation of RSVpreF vaccine in a phase 3 efficacy study. (Funded by Pfizer; EudraCT number, 2020-003887-21; ClinicalTrials.gov number, NCT04785612.).


Assuntos
Infecções por Vírus Respiratório Sincicial , Vacinas contra Vírus Sincicial Respiratório , Vírus Sincicial Respiratório Humano , Idoso , Anticorpos Neutralizantes/uso terapêutico , Anticorpos Antivirais , Humanos , Injeções Intramusculares , Infecções por Vírus Respiratório Sincicial/prevenção & controle , Vacinas contra Vírus Sincicial Respiratório/efeitos adversos , Eficácia de Vacinas
19.
N Engl J Med ; 386(17): 1615-1626, 2022 04 28.
Artigo em Inglês | MEDLINE | ID: mdl-35476650

RESUMO

BACKGROUND: Respiratory syncytial virus (RSV), a major cause of illness and death in infants worldwide, could be prevented by vaccination during pregnancy. The efficacy, immunogenicity, and safety of a bivalent RSV prefusion F protein-based (RSVpreF) vaccine in pregnant women and their infants are uncertain. METHODS: In a phase 2b trial, we randomly assigned pregnant women, at 24 through 36 weeks' gestation, to receive either 120 or 240 µg of RSVpreF vaccine (with or without aluminum hydroxide) or placebo. The trial included safety end points and immunogenicity end points that, in this interim analysis, included 50% titers of RSV A, B, and combined A/B neutralizing antibodies in maternal serum at delivery and in umbilical-cord blood, as well as maternal-to-infant transplacental transfer ratios. RESULTS: This planned interim analysis included 406 women and 403 infants; 327 women (80.5%) received RSVpreF vaccine. Most postvaccination reactions were mild to moderate; the incidence of local reactions was higher among women who received RSVpreF vaccine containing aluminum hydroxide than among those who received RSVpreF vaccine without aluminum hydroxide. The incidences of adverse events in the women and infants were similar in the vaccine and placebo groups; the type and frequency of these events were consistent with the background incidences among pregnant women and infants. The geometric mean ratios of 50% neutralizing titers between the infants of vaccine recipients and those of placebo recipients ranged from 9.7 to 11.7 among those with RSV A neutralizing antibodies and from 13.6 to 16.8 among those with RSV B neutralizing antibodies. Transplacental neutralizing antibody transfer ratios ranged from 1.41 to 2.10 and were higher with nonaluminum formulations than with aluminum formulations. Across the range of assessed gestational ages, infants of women who were immunized had similar titers in umbilical-cord blood and similar transplacental transfer ratios. CONCLUSIONS: RSVpreF vaccine elicited neutralizing antibody responses with efficient transplacental transfer and without evident safety concerns. (Funded by Pfizer; ClinicalTrials.gov number, NCT04032093.).


Assuntos
Infecções por Vírus Respiratório Sincicial , Vacinas contra Vírus Sincicial Respiratório , Vírus Sincicial Respiratório Humano , Proteínas Virais de Fusão , Hidróxido de Alumínio/efeitos adversos , Anticorpos Neutralizantes/sangue , Anticorpos Neutralizantes/imunologia , Anticorpos Antivirais/imunologia , Feminino , Humanos , Lactente , Gravidez , Infecções por Vírus Respiratório Sincicial/imunologia , Infecções por Vírus Respiratório Sincicial/prevenção & controle , Vacinas contra Vírus Sincicial Respiratório/efeitos adversos , Vacinas contra Vírus Sincicial Respiratório/imunologia , Vacinas contra Vírus Sincicial Respiratório/uso terapêutico , Vírus Sincicial Respiratório Humano/imunologia , Vacinação , Proteínas Virais de Fusão/imunologia
20.
J Infect Dis ; 226(7): 1204-1214, 2022 09 28.
Artigo em Inglês | MEDLINE | ID: mdl-35188974

RESUMO

BACKGROUND: A longitudinal study was performed to determine the breadth, kinetics, and correlations of systemic and mucosal antibody responses to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. METHODS: Twenty-six unvaccinated adults with confirmed coronavirus disease 2019 (COVID-19) were followed for 6 months with 3 collections of blood, nasal secretions, and stool. Control samples were obtained from 16 unvaccinated uninfected individuals. SARS-CoV-2 neutralizing and binding antibody responses were respectively evaluated by pseudovirus assays and multiplex bead arrays. RESULTS: Neutralizing antibody responses to SARS-CoV-2 were detected in serum and respiratory samples for 96% (25/26) and 54% (14/26), respectively, of infected participants. Robust binding antibody responses against SARS-CoV-2 spike protein and S1, S2, and receptor binding (RBD) domains occurred in serum and respiratory nasal secretions, but not in stool samples. Serum neutralization correlated with RBD-specific immunoglobulin (Ig)G, IgM, and IgA in serum (Spearman ρ = 0.74, 0.66, and 0.57, respectively), RBD-specific IgG in respiratory secretions (ρ = 0.52), disease severity (ρ = 0.59), and age (ρ = 0.40). Respiratory mucosal neutralization correlated with RBD-specific IgM (ρ = 0.42) and IgA (ρ = 0.63). CONCLUSIONS: Sustained antibody responses occurred after SARS-CoV-2 infection. Notably, there was independent induction of IgM and IgA binding antibody and neutralizing responses in systemic and respiratory compartments. These observations have implications for current vaccine strategies and understanding SARS-CoV-2 reinfection and transmission.


Assuntos
COVID-19 , Adulto , Anticorpos Neutralizantes , Anticorpos Antivirais , Humanos , Imunidade nas Mucosas , Imunoglobulina A , Imunoglobulina G , Imunoglobulina M , Estudos Longitudinais , SARS-CoV-2 , Glicoproteína da Espícula de Coronavírus
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