Publications by authors named "Jorge Kalil"

Introduction: The rapid development and deployment of multiple safe and effective COVID-19 vaccines were critical cornerstones of pandemic control. However, vaccine inequity and the emergence of new variants of concern (VOCs) highlighted major gaps in the global strategy to control SARS-CoV-2 infection. Despite the use of distinct platforms, most approved vaccines utilize the Spike protein as the main antigen due to its pivotal role in virus entry, mediated by the receptor binding domain (RBD).

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The novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), identified in late 2019, spurred a global pandemic, prompting an unprecedented international mobilization in vaccination and public health strategies. Although the pandemic is now under greater control, the worldwide dissemination of variants of concern (VOCs) has led to resistance and decreased vaccine efficacy, highlighting the urgent need for broad-spectrum therapeutic and preventive solutions. In this study, we employed hybridoma technology to generate monoclonal antibodies (mAbs) from mice immunized with the SARS-CoV-2 Wuhan Spike protein trimer.

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During the SARS-CoV-2 pandemic, the receptor-binding domain (RBD) of the spike protein emerged as a critical target for neutralizing antibodies. While immunoinformatics predicts binding sites, confirmation of epitope-antibody interactions remains a challenge. Here, we present a modular and highly sensitive square wave voltammetry immunosensor platform based on zinc oxide nanorods (ZnONRs) for detecting antibody responses to SARS-CoV-2 variant epitopes.

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COVID-19 pandemic continues to challenge the world with a major public health problem, long COVID (LC), which is estimated to affect over 400 million people worldwide. Many unknowns remain regarding the mechanisms involved in LC. We investigated the impact of anti-SARS-CoV-2 antibody and IFN-γ responses on the development of LC and its various phenotypes.

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Background: Atopic dermatitis (AD) is a chronic inflammatory skin disease that occurs more frequently in children but can also manifest in adults. Approximately 15-20% of children are affected worldwide. Persistent AD may be present in approximately 50% of patients during childhood.

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Introduction: Human infection with the protozoan causes Chagas disease, which may lead to a deadly dilated cardiomyopathy resulting from T-cell-mediated inflammation. We found that specific HLA-DRB1 alleles (*0103, *0402, *1301, and *1302) that display the DERAA motif are linked to this severe clinical manifestation of Chagas disease.

Methods: We employed computational analysis, functional assays, and single-cell RNA sequencing to determine the response of CD4+ T cells from indeterminate (IND) and cardiac (CCC) Chagas patients to peptides selected on DERAA-bearing alleles.

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Chagas disease, caused by the protozoan parasite (), is a neglected disease affecting around 6 million people, with no effective antiparasitic drugs or vaccines. About 40% of Chagas disease patients develop symptomatic forms in the chronic phase of infection, chronic Chagas cardiomyopathy (CCC) or digestive forms like megaoesophagus and megacolon, while most infected patients (60%) remain asymptomatic (ASY) in the so-called indeterminate form (IF). CCC is an inflammatory cardiomyopathy that occurs decades after the initial infection.

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The emergence of SARS-CoV-2 variants has reduced antibody effectiveness, affecting vaccine protection. This study evaluated neutralizing antibodies against Wuhan strain and several variants, including Alpha, Beta, Gamma, Delta, and Omicron, in Brazilians vaccinated twice with CoronaVac, ChAdOx1-S, or BNT162b2 before Delta and Omicron emerged. After the booster, strong antibody responses to the Wuhan strain were seen in all groups, but BNT162b2 resulted in higher anti-Spike and anti-RBD IgG levels.

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Background: Allergen immunotherapy is the only treatment that may modify the natural course of allergic diseases. Sublingual immunotherapy (SLIT) is a promising treatment, especially for children. Few studies currently exist related to optimal dosing for .

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Immunocompromised individuals were considered high-risk for severe disease due to SARS COV-2 infection. This study aimed to describe the safety of two doses of COVID-19 adsorbed inactivated vaccine (CoronaVac; Sinovac/Butantan), followed by additional doses of mRNA BNT162b2 (Pfizer/BioNTech) in immunocompromised (IC) adults, compared to immunocompetent/healthy (H) individuals. This phase 4, multicenter, open label study included solid organ transplant and hematopoietic stem cell transplant recipients, cancer patients and people with inborn errors of immunity with defects in antibody production, rheumatic, end-stage chronic kidney or liver disease, who were enrolled in the IC group.

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The COVID-19 pandemic has prompted a quest to understand why certain individuals remain uninfected or asymptomatic despite repetitive exposure to SARS-CoV-2. Here, we focused on six exposed females residing with their symptomatic and reinfected SARS-CoV-2 PCR-positive COVID-19 partners. Peripheral blood mononuclear cell samples from couples were analysed for poly (I:C)-induced mRNA expression of type I/III interferons and interferon-stimulated genes (ISGs).

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The aim of this study is to investigate the inflammasome dysregulation in peripheral blood leukocytes of VEXAS patients. The constitutive and in vitro triggered activation of inflammasome in PBMC and neutrophils was analyzed in two Brazilian patients with typical UBA1 mutations, and compared with healthy donors. Our findings highlight the constitutive activation of caspase-1 in VEXAS leukocytes, accompanied by increased plasma levels of IL-18.

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Protective immunity to dengue virus (DENV) requires antibody response to all four serotypes. Systems vaccinology identifies a multi-OMICs pre-vaccination signature and mechanisms predictive of broad antibody responses after immunization with a tetravalent live attenuated DENV vaccine candidate (Butantan-DV/TV003). Anti-inflammatory pathways, including TGF-β signaling expressed by CD68 monocytes, and the metabolites phosphatidylcholine (PC) and phosphatidylethanolamine (PE) positively correlate with broadly neutralizing antibody responses against DENV.

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Background: The Coronaviridae family comprises seven viruses known to infect humans, classified into alphacoronaviruses (HCoV-229E and HCoV-NL63) and betacoronaviruses (HCoV-OC43 and HCoV-HKU1), which are considered endemic. Additionally, it includes SARS-CoV (severe acute respiratory syndrome), MERS-CoV (Middle East respiratory syndrome), and the novel coronavirus SARS-CoV-2, responsible for COVID-19. SARS-CoV-2 induces severe respiratory complications, particularly in the elderly, immunocompromised individuals and those with underlying diseases.

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Hereditary angioedema (HAE) encompasses a group of diseases characterized by recurrent, genetically mediated angioedema associated with increased vascular permeability primarily due to bradykinin. The disease poses diagnostic challenges, leading to underdiagnosis and delayed therapy. Severe manifestations include laryngeal and intestinal angioedema, contributing to significant morbidity and mortality.

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Introduction: Post-COVID-19 condition (PCC) is characterised by a plethora of symptoms, with fatigue appearing as the most frequently reported. The alterations that drive both the persistent and post-acute disease newly acquired symptoms are not yet fully described. Given the lack of robust knowledge regarding the mechanisms of PCC we have examined the impact of inflammation in PCC, by evaluating serum cytokine profile and its potential involvement in inducing the different symptoms reported.

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Article Synopsis
  • Endometriosis is associated with elevated levels of soluble MICA (sMICA), which hinders the activity of natural killer (NK) cells, leading to decreased immune response.
  • Researchers measured sMICA in serum and peritoneal fluid and assessed NK cell function, discovering that higher sMICA levels correlate with advanced endometriosis and impaired NK cell effectiveness.
  • The study suggests that sMICA plays a significant role in the progression of endometriosis by causing defects in NK cell activity and contributing to the persistence of ectopic endometrial tissue.
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Article Synopsis
  • Operation Warp Speed was a U.S. initiative aimed at speeding up the development of Covid-19 vaccines through collaboration and funding.
  • The National Institutes of Health managed a data and safety monitoring board that was responsible for overseeing the trials associated with Operation Warp Speed.
  • The article highlights the difficulties encountered in monitoring these vaccine trials and suggests strategies for improving similar efforts in the future.
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Background: Butantan-Dengue Vaccine (Butantan-DV) is an investigational, single-dose, live, attenuated, tetravalent vaccine against dengue disease, but data on its overall efficacy are needed.

Methods: In an ongoing phase 3, double-blind trial in Brazil, we randomly assigned participants to receive Butantan-DV or placebo, with stratification according to age (2 to 6 years, 7 to 17 years, and 18 to 59 years); 5 years of follow-up is planned. The objectives of the trial were to evaluate overall vaccine efficacy against symptomatic, virologically confirmed dengue of any serotype occurring more than 28 days after vaccination (the primary efficacy end point), regardless of serostatus at baseline, and to describe safety up to day 21 (the primary safety end point).

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Chagas disease (CD), caused by the protozoan parasite , is a neglected disease affecting around 6 million people. About 30% of CD patients develop chronic Chagas disease cardiomyopathy (CCC), an inflammatory cardiomyopathy that occurs decades after the initial infection, while most infected patients (60%) remain asymptomatic in the so-called indeterminate form (IF). Death results from heart failure or arrhythmia in a subset of CCC patients.

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Parasitemia and inflammatory markers are cross-sectionally associated with chronic Chagas cardiomyopathy (CCC) among patients with . However, the prospective association of the parasite load and host immune response-related characteristics with CCC (that is, progressors) among seropositive individuals has only been partially defined. In a cohort of seropositive patients in Montes Claros and São Paulo, Brazil who were followed over 10 years, we identified the association of a baseline parasite load and systemic markers of inflammation with a decline in cardiac function and/or the presence of cardiac congestion 10 years later.

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