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1.
Cureus ; 16(4): e59104, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38803727

RESUMO

Myasthenia gravis (MG) is an autoimmune illness characterized by autoantibodies against the acetylcholine receptor (AChR), muscle-specific tyrosine kinase (MuSK), and an increasing number of extra postsynaptic proteins. Pathogenic autoantibodies reduce the number of functional AChRs in the neuromuscular junction's (NMJ) muscle end plate. The cause of the autoimmune response is unknown, but thymic abnormalities and immune regulatory deficiencies are significant. The disease's incidence is likely influenced by genetic predisposition, with sex hormones and exercise playing a role. MG can affect any age, race, or gender and can be caused by any stressor, with infections being the most frequent cause. Treatment focuses on airway support and the triggering incident. MG is a rare autoimmune disease causing fatigue-inducing weakness in the axial, respiratory, leg, and bulbar muscles. Initially affecting the eyes, most MG patients experience at least one worsening symptom during their illness. The disease is mainly caused by antibodies against the AChR, dependence on the immune system within cells, and engagement of the complement system. The complement system plays a significant role in MG, and complement inhibition can both prevent the onset and slow its development. Ocular MG affects around 15% of people, with most patients having blocking antibodies against the cholinergic receptor. There may be correlations between thymoma and other autoimmune conditions, especially thyroid illness. Treatment and management for MG involve removing autoantibodies from circulation or blocking effector mechanisms using techniques such as complement inhibition, plasmapheresis, and B-cell elimination.

2.
Cureus ; 16(3): e56937, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38665749

RESUMO

The Triple "O" model in educational research, meaning the Objectives, Operations, and Outcomes model, is a plan to dive into how research works. Objectives are the reasons for this research, directing what researchers aim to explore. Operations focus on transforming these reasons into actual steps; they navigate the methods for gathering information. As for the Outcomes, they represent significant shifts resulting from the research, such as improved methods of teaching or students achieving their educational targets with better learning outcomes. Using the Triple "O" model, researchers are expected to explore educational research and studies significantly and effectively. This model provides a clear plan on how to conduct research and pay attention to the results. It is ready to change the whole scene of educational research and make good, important differences in learning.

3.
Cureus ; 16(3): e56214, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38618417

RESUMO

In this article, we discuss the ethics of veganism by looking at the moral implications of having a vegan diet or plant-based diet. Veganism is a way of diet that forbids or avoids consuming any animal products. It has drawn a lot of interest recently due to awareness or trends of vegan diet, human health, and ethical behavior benefits. The aim of the research is to look into the moral values that talk about veganism, such as animal welfare, environmental sustainability, and human welfare. In this study, we conduct a thorough assessment of ethical theories and actual evidence in an effort to know about the ethical reasons for veganism and its larger societal impacts. Through an analysis of existing literature and clinical studies, we discuss the various challenges, advantages, lifestyle modification, and nutritional concerns related to a vegan diet.

4.
Cureus ; 16(1): e52727, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-38384651

RESUMO

A suitable portion of the total population still suffers through acne vulgaris, a widespread dermatological illness that mostly affects teens and young adults. Although acne is typically considered to be a cosmetic problem, recent research has concluded that certainly it has a significant role on impacting many physiological aspects of human health. This thorough investigation attempts to examine the intricate effects of acne on human physiology, taking into consideration both systemic and local effects. The study synthesizes research from a number of scientific disciplines, including dermatology, endocrinology, immunology, and psychoneuroimmunology. It investigates the complex interrelationships between several factors, such as sebum production, follicular hyperkeratinization, hormone imbalance, and Propionibacterium acnes colonisation, that lead to the development of acne. The study also sheds information on the intricate physiological mechanisms, oxidative stress, and immune response that contribute to the aetiology of acne. Along with it, the review investigates the relationship between endocrine problems and acne, emphasizing hormonal anomalies and their possible role in acne severity. The psychological effects of acne are also discussed, including the psychological problems, concerns with self-esteem, and decreased quality of life that acne sufferers encounter. On comprehensively examining the diverse physiological aspects affected by acne, this review provides a foundation for future research endeavours and informs the development of targeted therapeutic interventions. Ultimately, the integration of multidisciplinary approaches will enable healthcare professionals to address the physiological complexities of acne and improve the overall well-being of individuals affected by this common skin condition.

5.
Cureus ; 15(1): e34027, 2023 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-36814731

RESUMO

Ulcerative colitis (UC) causes diffuse friability and superficial wall degeneration that is accompanied by bleeding. UC, now recognized as a global illness, affects millions of people globally. The most effective treatment for UC is Ileal Pouch Anal Anastomosis (IPAA). Many medical experts and patients favor proctocolectomy with IPAA because it improves bowel function and allows feces to pass via the anus. Considering the most recent research, systematic reviews, statistical analysis, and recommendations, a selective literature search was carried out. The database used was PubMed. The current work provides a summary of surgical alternatives, results, and pre-and postoperative treatment for UC patients. In the course of their illness, about 30% of UC patients will need surgery. Due to its natural limitation to the colon and rectum, UC may mostly be treated surgically. The preferred surgical process is a restorative proctocolectomy with an IPAA. A 30% postoperative complication rate and a 0.1% death rate for this operation are both shown in large studies. One of the biggest things preventing UC from being successfully treated surgically is pouchitis. A long-run success rate of the pouch is >90% after 10 follow-ups, despite a significant surgical complication rate. For patients with UC to have the best possible outcome, extensive collaboration among the various specialties in the pre and postoperative context is crucial. In skilled centers, more than 90% of the total patients can eventually achieve a decent quality of life despite a 30% likelihood of early postoperative problems. UC patients may be cured with proctocolectomy, but there is a risk of morbidity that must be considered, especially in pediatric patients. As a result of advancements in our comprehension of the pathogenic mechanisms causing UC, new therapies have been proposed, the most significant change being the emergence of anti-tumor necrosis factor (TNF) medications.

6.
PLoS Pathog ; 18(12): e1010994, 2022 12.
Artigo em Inglês | MEDLINE | ID: mdl-36508467

RESUMO

The emergence of new variants of SARS-CoV-2 necessitates unremitting efforts to discover novel therapeutic monoclonal antibodies (mAbs). Here, we report an extremely potent mAb named P4A2 that can neutralize all the circulating variants of concern (VOCs) with high efficiency, including the highly transmissible Omicron. The crystal structure of the P4A2 Fab:RBD complex revealed that the residues of the RBD that interact with P4A2 are a part of the ACE2-receptor-binding motif and are not mutated in any of the VOCs. The pan coronavirus pseudotyped neutralization assay confirmed that the P4A2 mAb is specific for SARS-CoV-2 and its VOCs. Passive administration of P4A2 to K18-hACE2 transgenic mice conferred protection, both prophylactically and therapeutically, against challenge with VOCs. Overall, our data shows that, the P4A2 mAb has immense therapeutic potential to neutralize the current circulating VOCs. Due to the overlap between the P4A2 epitope and ACE2 binding site on spike-RBD, P4A2 may also be highly effective against a number of future variants.


Assuntos
Enzima de Conversão de Angiotensina 2 , Anticorpos Neutralizantes , COVID-19 , SARS-CoV-2 , Animais , Humanos , Camundongos , Enzima de Conversão de Angiotensina 2/química , Anticorpos Monoclonais/uso terapêutico , Anticorpos Neutralizantes/uso terapêutico , Anticorpos Antivirais/uso terapêutico , COVID-19/imunologia , COVID-19/terapia , Camundongos Transgênicos , Testes de Neutralização , SARS-CoV-2/genética , SARS-CoV-2/imunologia , Glicoproteína da Espícula de Coronavírus/genética
7.
Vaccines (Basel) ; 10(10)2022 Oct 20.
Artigo em Inglês | MEDLINE | ID: mdl-36298628

RESUMO

The underlying factors contributing to the evolution of SARS-CoV-2-specific T cell responses during COVID-19 infection remain unidentified. To address this, we characterized innate and adaptive immune responses with metabolomic profiling longitudinally at three different time points (0-3, 7-9, and 14-16 days post-COVID-19 positivity) from young, mildly symptomatic, active COVID-19 patients infected during the first wave in mid-2020. We observed that anti-RBD IgG and viral neutralization are significantly reduced against the delta variant, compared to the ancestral strain. In contrast, compared to the ancestral strain, T cell responses remain preserved against the delta and omicron variants. We determined innate immune responses during the early stage of active infection, in response to TLR 3/7/8-mediated activation in PBMCs and serum metabolomic profiling. Correlation analysis indicated PBMCs-derived proinflammatory cytokines, IL-18, IL-1ß, and IL-23, and the abundance of plasma metabolites involved in arginine biosynthesis were predictive of a robust SARS-CoV-2-specific Th1 response at a later stage (two weeks after PCR positivity). These observations may contribute to designing effective vaccines and adjuvants that promote innate immune responses and metabolites to induce a long-lasting anti-SARS-CoV-2-specific T cell response.

9.
ACS Infect Dis ; 8(10): 2119-2132, 2022 10 14.
Artigo em Inglês | MEDLINE | ID: mdl-36129193

RESUMO

The engineering of virus-like particles (VLPs) is a viable strategy for the development of vaccines and for the identification of therapeutic targets without using live viruses. Here, we report the generation and characterization of quadruple-antigen SARS-CoV-2 VLPs. VLPs were generated by transient transfection of two expression cassettes in adherent HEK293T cells─one cassette containing Mpro for processing of three structural proteins (M, E, and N), and the second cassette expressing the Spike protein. Further characterization revealed that the VLPs retain close morphological and antigenic similarity with the native virus and also bind strongly to the SARS-CoV-2 receptor hACE-2 in an in vitro binding assay. Interestingly, the VLPs were found to internalize into U87-MG cells through cholesterol-rich domains in a dynamin-dependent process. Finally, our results showed that mice immunized with VLPs induce robust humoral and cellular immune responses mediated by enhanced levels of IL-4, IL-17, and IFNγ. Taken together, our results demonstrate that VLPs mimic the native virus and induce a strong immune response, indicating the possible use of these particles as an alternative vaccine candidate against SARS-CoV-2. VLPs can also be effective in mapping the initial stages of virus entry and screening inhibitors.


Assuntos
COVID-19 , SARS-CoV-2 , Animais , COVID-19/prevenção & controle , Células HEK293 , Humanos , Interleucina-17 , Interleucina-4 , Camundongos , Glicoproteína da Espícula de Coronavírus/genética , Internalização do Vírus
10.
3 Biotech ; 12(9): 202, 2022 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-35928502

RESUMO

We used human semi-synthetic phage antibody gene libraries to select anti-SARS-CoV-2 RBD scFv antibody fragment and subsequent characterization of this novel tetravalent monoclonal antibody targeting conformational epitopes in the receptor binding domain of SARS-CoV-2. Binding studies suggest that II62 tetravalent antibody cross-reacts with RBD protein of SARS-CoV2 and its different variants of concerns. The epitope mapping data reveals that II62 tetravalent antibody targets an epitope that does not directly interferes with RBD: ACE2 interaction. Neutralization studies with live authentic SARS-CoV2 virus suggests that increase in valency of II62 mAb from monovalent to tetravalent doesn't perturbate virus interactions with the ACE2 expressing host cells in cytopathic effect-based (CPE) assay. Supplementary Information: The online version contains supplementary material available at 10.1007/s13205-022-03272-6.

11.
Int J Biol Macromol ; 217: 19-26, 2022 Sep 30.
Artigo em Inglês | MEDLINE | ID: mdl-35817240

RESUMO

Dengue virus is transmitted by Aedes mosquitoes and dengue is endemic in many regions of the world. Severe dengue results in complications that may lead to death. Although some vaccine candidates are in clinical trials and one vaccine Dengvaxia, with restricted efficacy, is available, there are currently no specific therapies to completely prevent or treat dengue. The dengue virus structural protein E (envelope) exists as a head-to-tail dimer on mature virus, is targeted by broadly neutralizing antibodies and is suitable for developing vaccine immunogens. Here, we have used a redesigned dengue prME expression construct and immunoaffinity chromatography with conformational/quaternary antibody A11 to purify soluble DENV4 sE(A259C) (E ectodomain) dimers from mammalian expression system to ~99 % purity. These dimers retain glycosylation reported for native DENV E, display the three major broadly neutralizing antibody epitopes, and form well-ordered structure. This strategy can be used for developing subunit vaccine candidates against dengue and other flaviviruses.


Assuntos
Vírus da Dengue , Dengue , Animais , Anticorpos Neutralizantes , Anticorpos Antivirais , Dengue/prevenção & controle , Vírus da Dengue/genética , Vírus da Dengue/metabolismo , Humanos , Mamíferos/metabolismo , Proteínas do Envelope Viral/metabolismo
12.
Nat Microbiol ; 7(7): 974-985, 2022 07.
Artigo em Inglês | MEDLINE | ID: mdl-35681012

RESUMO

BBV152 is a whole-virion inactivated vaccine based on the Asp614Gly variant. BBV152 is the first alum-imidazoquinolin-adjuvanted vaccine authorized for use in large populations. Here we characterized the magnitude, quality and persistence of cellular and humoral memory responses up to 6 months post vaccination. We report that the magnitude of vaccine-induced spike and nucleoprotein antibodies was comparable with that produced after infection. Receptor binding domain-specific antibodies declined against variants in the order of Alpha (B.1.1.7; 3-fold), Delta (B.1.617.2; 7-fold) and Beta (B.1.351; 10-fold). However, pseudovirus neutralizing antibodies declined up to 2-fold against the Delta followed by the Beta variant (1.7-fold). Vaccine-induced memory B cells were also affected by the Delta and Beta variants. The SARS-CoV-2-specific multicytokine-expressing CD4+ T cells were found in ~85% of vaccinated individuals. Only a ~1.3-fold reduction in efficacy was observed in CD4+ T cells against the Beta variant. We found that antigen-specific CD4+ T cells were present in the central memory compartment and persisted for at least up to 6 months post vaccination. Vaccine-induced CD8+ T cells were detected in ~50% of individuals. Importantly, the vaccine was capable of inducing follicular T helper cells that exhibited B-cell help potential. These findings show that inactivated vaccine BBV152 induces robust immune memory to SARS-CoV-2 and variants of concern that persists for at least 6 months after vaccination.


Assuntos
COVID-19 , Vacinas Virais , Linfócitos T CD8-Positivos , COVID-19/prevenção & controle , Vacinas contra COVID-19 , Humanos , Memória Imunológica , SARS-CoV-2 , Vacinas de Produtos Inativados , Vírion
13.
Elife ; 112022 01 11.
Artigo em Inglês | MEDLINE | ID: mdl-35014610

RESUMO

Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection in the Golden Syrian hamster causes lung pathology that resembles human coronavirus disease (COVID-19). However, extrapulmonary pathologies associated with SARS-CoV-2 infection and post-COVID sequelae remain to be understood. Here, we show, using a hamster model, that the early phase of SARS-CoV-2 infection leads to an acute inflammatory response and lung pathologies, while the late phase of infection causes cardiovascular complications (CVCs) characterized by ventricular wall thickening associated with increased ventricular mass/body mass ratio and interstitial coronary fibrosis. Molecular profiling further substantiated our findings of CVC as SARS-CoV-2-infected hamsters showed elevated levels of serum cardiac troponin I, cholesterol, low-density lipoprotein, and long-chain fatty acid triglycerides. Serum metabolomics profiling of SARS-CoV-2-infected hamsters identified N-acetylneuraminate, a functional metabolite found to be associated with CVC, as a metabolic marker was found to be common between SARS-CoV-2-infected hamsters and COVID-19 patients. Together, we propose hamsters as a suitable animal model to study post-COVID sequelae associated with CVC, which could be extended to therapeutic interventions.


Assuntos
COVID-19 , Doenças Cardiovasculares , SARS-CoV-2/metabolismo , Animais , COVID-19/sangue , COVID-19/complicações , COVID-19/patologia , Doenças Cardiovasculares/sangue , Doenças Cardiovasculares/etiologia , Doenças Cardiovasculares/patologia , Doenças Cardiovasculares/virologia , Colesterol/sangue , Modelos Animais de Doenças , Feminino , Humanos , Lipoproteínas LDL/sangue , Mesocricetus , Triglicerídeos/sangue , Troponina I/sangue
14.
Lancet Infect Dis ; 22(4): 473-482, 2022 04.
Artigo em Inglês | MEDLINE | ID: mdl-34838183

RESUMO

BACKGROUND: SARS-CoV-2 variants of concern (VOCs) have threatened COVID-19 vaccine effectiveness. We aimed to assess the effectiveness of the ChAdOx1 nCoV-19 vaccine, predominantly against the delta (B.1.617.2) variant, in addition to the cellular immune response to vaccination. METHODS: We did a test-negative, case-control study at two medical research centres in Faridabad, India. All individuals who had a positive RT-PCR test for SARS-CoV-2 infection between April 1, 2021, and May 31, 2021, were included as cases and individuals who had a negative RT-PCR test were included as controls after matching with cases on calendar week of RT-PCR test. The primary outcome was effectiveness of complete vaccination with the ChAdOx1 nCoV-19 vaccine against laboratory-confirmed SARS-CoV-2 infection. The secondary outcomes were effectiveness of a single dose against SARS-CoV-2 infection and effectiveness of a single dose and complete vaccination against moderate-to-severe disease among infected individuals. Additionally, we tested in-vitro live-virus neutralisation and T-cell immune responses to the spike protein of the wild-type SARS-CoV-2 and VOCs among healthy (anti-nucleocapsid antibody negative) recipients of the ChAdOx1 nCoV-19 vaccine. FINDINGS: Of 2379 cases of confirmed SARS-CoV-2 infection, 85 (3·6%) were fully vaccinated compared with 168 (8·5%) of 1981 controls (adjusted OR [aOR] 0·37 [95% CI 0·28-0·48]), giving a vaccine effectiveness against SARS-CoV-2 infection of 63·1% (95% CI 51·5-72·1). 157 (6·4%) of 2451 of cases and 181 (9·1%) of 1994) controls had received a single dose of the ChAdOx1 nCoV-19 vaccine (aOR 0·54 [95% CI 0·42-0·68]), thus vaccine effectiveness of a single dose against SARS-CoV-2 infection was 46·2% (95% CI 31·6-57·7). One of 84 cases with moderate-to-severe COVID-19 was fully vaccinated compared with 84 of 2295 cases with mild COVID-19 (aOR 0·19 [95% CI 0·01-0·90]), giving a vaccine effectiveness of complete vaccination against moderate-to-severe disease of 81·5% (95% CI 9·9-99·0). The effectiveness of a single dose against moderate-to-severe disease was 79·2% (95% CI 46·1-94·0); four of 87 individuals with moderate-to-severe COVID-19 had received a single dose compared with 153 of 2364 participants with mild disease (aOR 0·20 [95% CI 0·06-0·54]). Among 49 healthy, fully vaccinated individuals, neutralising antibody responses were lower against the alpha (B.1.1.7; geometric mean titre 244·7 [95% CI 151·8-394·4]), beta (B.1.351; 97·6 [61·2-155·8]), kappa (B.1.617.1; 112·8 [72·7-175·0]), and delta (88·4 [61·2-127·8]) variants than against wild-type SARS-CoV-2 (599·4 [376·9-953·2]). However, the antigen-specific CD4 and CD8 T-cell responses were conserved against both the delta variant and wild-type SARS-CoV-2. INTERPRETATION: The ChAdOx1 nCoV-19 vaccine remained effective against moderate-to-severe COVID-19, even during a surge that was dominated by the highly transmissible delta variant of SARS-CoV-2. Spike-specific T-cell responses were maintained against the delta variant. Such cellular immune protection might compensate for waning humoral immunity. FUNDING: Department of Biotechnology India, Council of Scientific and Industrial Research India, and Fondation Botnar.


Assuntos
COVID-19 , SARS-CoV-2 , Formação de Anticorpos , COVID-19/epidemiologia , COVID-19/prevenção & controle , Vacinas contra COVID-19 , Estudos de Casos e Controles , ChAdOx1 nCoV-19 , Humanos , Vacinação
15.
Int Immunopharmacol ; 101(Pt B): 108187, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34649114

RESUMO

Cross-reactivity among the two diverse viruses is believed to originate from the concept of antibodies recognizing similar epitopes on the two viral surfaces. Cross-reactive antibody responses have been seen in previous variants of SARS and SARS-CoV-2, but little is known about the cross reactivity with other similar RNA viruses like HIV-1. In the present study, we examined the reactivity the SARS-CoV-2 directed antibodies, via spike, immunized mice sera and demonstrated whether they conferred any cross-reactive neutralization against HIV-1. Our findings show that SARS-CoV-2 spike immunized mice antibodies cross-react with the HIV-1 Env protein. Cross-neutralization among the two viruses is uncommon, suggesting the presence of a non-neutralizing antibody response to conserved epitopes amongst the two viruses. Our results indicate, that SARS-CoV-2 spike antibody cross reactivity is targeted towards the gp41 region of the HIV-1 Env (gp160) protein. Overall, our investigation not only answers a crucial question about the understanding of cross-reactive epitopes of antibodies generated in different viral infections, but also provides critical evidence for developing vaccine immunogens and novel treatment strategies with enhanced efficacy capable of recognising diverse pathogens with similar antigenic features.


Assuntos
Anticorpos Antivirais/imunologia , Proteína gp41 do Envelope de HIV/imunologia , Glicoproteína da Espícula de Coronavírus/imunologia , Animais , Reações Cruzadas , Camundongos Endogâmicos BALB C , Camundongos Endogâmicos C57BL , Proteínas Recombinantes/imunologia , Glicoproteína da Espícula de Coronavírus/genética
16.
Appl Microbiol Biotechnol ; 105(16-17): 6315-6332, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-34423407

RESUMO

The route of administration of a therapeutic agent has a substantial impact on its success. Therapeutic antibodies are usually administered systemically, either directly by intravenous route, or indirectly by intramuscular or subcutaneous injection. However, treatment of diseases contained within a specific tissue necessitates a better alternate route of administration for targeting localised infections. Inhalation is a promising non-invasive strategy for antibody delivery to treat respiratory maladies because it provides higher concentrations of antibody in the respiratory airways overcoming the constraints of entry through systemic circulation and uncertainity in the amount reaching the target tissue. The nasal drug delivery route is one of the extensively researched modes of administration, and nasal sprays for molecular drugs are deemed successful and are presently commercially marketed. This review highlights the current state and future prospects of inhaled therapies, with an emphasis on the use of monoclonal antibodies for the treatment of respiratory infections, as well as an overview of their importance, practical challenges, and clinical trial outcomes.Key points• Immunologic strategies for preventing mucosal transmission of respiratory pathogens.• Mucosal-mediated immunoprophylaxis could play a major role in COVID-19 prevention.• Applications of monoclonal antibodies in passive immunisation.


Assuntos
COVID-19 , Anticorpos Monoclonais/uso terapêutico , Humanos , Imunização Passiva , Imunoterapia , SARS-CoV-2
17.
Int Immunopharmacol ; 99: 108020, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34426117

RESUMO

The spike protein of the SARS-CoV-2 virus is the foremost target for the designing of vaccines and therapeutic antibodies and also acts as a crucial antigen in the assessment of COVID-19 immune responses. The enveloped viruses; such as SARS-CoV-2, Human Immunodeficiency Virus-1 (HIV-1) and influenza, often hijack host-cell glycosylation pathways and influence pathobiology and immune selection. These glycan motifs can lead to either immune evasion or viral neutralization by the production of cross-reactive antibodies that can lead to antibody-dependent enhancement (ADE) of infection. Potential cross-protection from influenza vaccine has also been reported in COVID-19 infected individuals in several epidemiological studies recently; however, the scientific basis for these observations remains elusive. Herein, we show that the anti-SARS-CoV2 antibodies cross-reacts with the Hemagglutinin (HA) protein. This phenomenon is common to both the sera from convalescent SARS-CoV-2 donors and spike immunized mice, although these antibodies were unable to cross-neutralize, suggesting the presence of a non-neutralizing antibody response. Epitope mapping suggests that the cross-reactive antibodies are targeted towards glycan epitopes of the SARS-CoV-2 spike and HA. Overall, our findings address the cross-reactive responses, although non-neutralizing, elicited against RNA viruses and warrant further studies to investigate whether such non-neutralizing antibody responses can contribute to effector functions such as antibody-dependent cellular cytotoxicity (ADCC) or ADE.


Assuntos
COVID-19/imunologia , Reações Cruzadas/imunologia , Glicoproteínas de Hemaglutininação de Vírus da Influenza/imunologia , Glicoproteína da Espícula de Coronavírus/imunologia , Animais , Anticorpos Neutralizantes , Reações Antígeno-Anticorpo , Sítios de Ligação de Anticorpos/imunologia , Técnicas de Cultura de Células , Chlorocebus aethiops , Cães , Mapeamento de Epitopos , Epitopos/imunologia , Glicosilação , Humanos , Vacinas contra Influenza/imunologia , Células Madin Darby de Rim Canino , Glicoproteínas de Membrana/metabolismo , Camundongos , Camundongos Endogâmicos C57BL , SARS-CoV-2/imunologia , Células Vero
18.
Mol Ther Nucleic Acids ; 26: 321-332, 2021 Dec 03.
Artigo em Inglês | MEDLINE | ID: mdl-34188971

RESUMO

The recent SARS-CoV-2 outbreak has been declared a global health emergency. It will take years to vaccinate the whole population to protect them from this deadly virus, hence the management of SARS-CoV-2 largely depends on the widespread availability of an accurate diagnostic test. Toward addressing the unmet need of a reliable diagnostic test in the current work by utilizing the power of Systematic Evolution of Ligands by EXponential enrichment, a 44-mer G-quadruplex-forming DNA aptamer against spike trimer antigen of SARS-CoV-2 was identified. The lead aptamer candidate (S14) was characterized thoroughly for its binding, selectivity, affinity, structure, and batch-to-batch variability by utilizing various biochemical, biophysical, and in silico techniques. S14 has demonstrated a low nanomolar KD, confirming its tight binding to a spike antigen of SARS-CoV-2. S14 can detect as low as 2 nM of antigen. The clinical evaluation of S14 aptamer on nasopharyngeal swab specimens (n = 232) has displayed a highly discriminatory response between SARS-CoV-2 infected individuals from the non-infected one with a sensitivity and specificity of ∼91% and 98%, respectively. Importantly, S14 aptamer-based test has evinced a comparable performance with that of RT-PCR-based assay. Altogether, this study established the utility of aptamer technology for the detection of SARS-CoV-2.

19.
Front Immunol ; 12: 641447, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34108961

RESUMO

The newly emerged novel coronavirus, SARS-CoV-2, the causative agent of COVID-19 has proven to be a threat to the human race globally, thus, vaccine development against SARS-CoV-2 is an unmet need driving mass vaccination efforts. The receptor binding domain of the spike protein of this coronavirus has multiple neutralizing epitopes and is associated with viral entry. Here we have designed and characterized the SARS-CoV-2 spike protein fragment 330-526 as receptor binding domain 330-526 (RBD330-526) with two native glycosylation sites (N331 and N343); as a potential subunit vaccine candidate. We initially characterized RBD330-526 biochemically and investigated its thermal stability, humoral and T cell immune response of various RBD protein formulations (with or without adjuvant) to evaluate the inherent immunogenicity and immunomodulatory effect. Our result showed that the purified RBD immunogen is stable up to 72 h, without any apparent loss in affinity or specificity of interaction with the ACE2 receptor. Upon immunization in mice, RBD generates a high titer humoral response, elevated IFN-γ producing CD4+ cells, cytotoxic T cells, and robust neutralizing antibodies against live SARS-CoV-2 virus. Our results collectively support the potential of RBD330-526 as a promising vaccine candidate against SARS-CoV-2.


Assuntos
Anticorpos Antivirais/sangue , Vacinas contra COVID-19/administração & dosagem , Imunidade Humoral/efeitos dos fármacos , Imunogenicidade da Vacina , Fragmentos de Peptídeos/administração & dosagem , Glicoproteína da Espícula de Coronavírus/administração & dosagem , Células Th1/efeitos dos fármacos , Adjuvantes Imunológicos/administração & dosagem , Animais , Biomarcadores/sangue , Vacinas contra COVID-19/imunologia , Chlorocebus aethiops , Estabilidade de Medicamentos , Glicosilação , Células HEK293 , Humanos , Imunização , Interferon gama/sangue , Masculino , Camundongos Endogâmicos C57BL , Fragmentos de Peptídeos/imunologia , Domínios e Motivos de Interação entre Proteínas , Estabilidade Proteica , Glicoproteína da Espícula de Coronavírus/imunologia , Células Th1/imunologia , Células Th1/metabolismo , Vacinas de Subunidades Antigênicas/administração & dosagem , Vacinas de Subunidades Antigênicas/imunologia , Células Vero
20.
Am J Trop Med Hyg ; 105(1): 66-72, 2021 05 18.
Artigo em Inglês | MEDLINE | ID: mdl-34003792

RESUMO

Clinical and epidemiological characteristics of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are now widely available, but there are few data regarding longitudinal serology in large cohorts, particularly those from low-income and middle-income countries. We established an ongoing prospective cohort of 3,840 SARS-CoV-2-positive individuals according to RT-PCR in the Delhi-National Capital Region of India to document clinical and immunological characteristics during illness and convalescence. The immunoglobulin G (IgG) responses to the receptor binding domain (RBD) and nucleocapsid were assessed at 0 to 7 days, 10 to 28 days, and 6 to 10 weeks after infection. The clinical predictors of seroconversion were identified by multivariable regression analysis. The seroconversion rates during the postinfection windows of 0 to 7 days, 10 to 28 days, and 6 to 10 weeks were 46%, 84.7%, and 85.3%, respectively (N = 743). The proportion with a serological response increased with the severity of coronavirus disease 2019 (COVID-19). All participants with severe disease, 89.6% with mild to moderate infection, and 77.3% of asymptomatic participants had IgG antibodies to the RBD antigen. The threshold values for the nasopharyngeal viral RNA RT-PCR of a subset of asymptomatic and symptomatic seroconverters were comparable (P = 0.48) to those of nonseroconverters (P = 0.16) (N = 169). This is the first report of longitudinal humoral immune responses to SARS-CoV-2 over a period of 10 weeks in South Asia. The low seropositivity of asymptomatic participants and differences between assays highlight the importance of contextualizing the understanding of population serosurveys.


Assuntos
COVID-19/sangue , COVID-19/virologia , SARS-CoV-2 , Adolescente , Adulto , Anticorpos Antivirais/sangue , COVID-19/epidemiologia , Criança , Pré-Escolar , Estudos de Coortes , Feminino , Humanos , Imunoglobulina G/sangue , Índia/epidemiologia , Lactente , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Fatores de Risco , SARS-CoV-2/imunologia , Soroconversão , Adulto Jovem
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