Search

The use of graphene quantum dots as biomedical devices and drug delivery systems has been increasing. The nano-platform of pure carbon has shown unique properties and is approved to be safe for human use. In this study, we successfully produced and characterized folic acid-functionalized graphene quantum dots (GQD-FA) to evaluate their antiviral activity against Zika virus (ZIKV) infection in vitro, and for radiolabeling with the alpha -particle emitting radionuclide radium-223. The in vitro results exhibited the low cytotoxicity of the nanoprobe GQD-FA in Vero E6 cells and the antiviral effect against replication of the ZIKV infection. In addition, our findings demonstrated that functionalization with folic acid doesn't improve the antiviral effect of graphene quantum dots against ZIVK replication in vitro. On the other hand, the radiolabeled nanoprobe 223Ra@GQD-FA was also produced as confirmed by the Energy Dispersive X-Ray Spectroscopy analysis. 223Ra@GQD-FA might expand the application of alpha targeted therapy using radium-223 in folate receptor-overexpressing tumors., Carlos Chagas Filho Foundation for Research Support of Rio de Janeiro State (FAPERJ) [E-26/200.815/2021, E-26/010.000981/2019, E-26/010.002362/2019, E-26/211.269/2021, E-26//211.207/2021, E-26/202.320/2021]; CNPq [301069/2018-2]; National Nuclear Energy Commission [01341.011064/2021-71], This study was funded by Carlos Chagas Filho Foundation for Research Support of Rio de Janeiro State (FAPERJ) (Cientista do Nosso Estado: E-26/200.815/2021; Rede NanoSaude: E-26/010.000981/2019, Pesquisa na UEZO: E-26/010.002362/2019; Tematicos: E-26/211.269/2021, Infraestrutura e Pesquisa na UEZO e UERJ: E-26//211.207/2021, Bolsa de Pos Doutorado Senior (PDS): E-26/202.320/2021) CNPq (Bolsa de Produtividade 1B: 301069/2018-2) to Ralph Santos-Oliveira. National Nuclear Energy Commission (Bolsa de Posdoutorado CNEN: 01341.011064/2021-71) to Martha Sahyli Ortega Pijeira.

Adaptive immunity in severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection is decisive for disease control. Delayed activation of T cells is associated with a worse outcome in coronavirus disease 2019 (COVID-19). Although convalescent individuals exhibit solid T-cell immunity, to date, long-term immunity to SARS-CoV-2 is still under investigation.We aimed to characterize the specific T-cell response on the basis of theThe sequence of the SARS-CoV-2 genome was screened, leading to the identification of specific and promiscuous peptides predicted to be recognized by CD4Our results indicated heterogeneous T-cell responsiveness among the participants. Compared with patients who exhibited mild symptoms, hospitalized patients had a significantly higher magnitude of response. In addition, male and older patients showed a lower number of IFN-γ-producing cells. Analysis of samples collected after 180 days revealed a reduction in the number of specific circulating IFN-γ-producing T cells, suggesting decreased immunity against viral peptides.Our data are evidence that

Over the last few decades, several emerging or reemerging viral diseases with no readily available vaccines have ravaged the world. A platform to fastly generate vaccines inducing potent and durable neutralizing antibody and T cell responses is sorely needed. Bioinformatically identified epitope-based vaccines can focus on immunodominant T cell epitopes and induce more potent immune responses than a whole antigen vaccine and may be deployed more rapidly and less costly than whole-gene vaccines. Increasing evidence has shown the importance of the CD4+ T cell response in protection against HIV and other viral infections. The previously described DNA vaccine HIVBr18 encodes 18 conserved, promiscuous epitopes binding to multiple HLA-DR-binding HIV epitopes amply recognized by HIV-1-infected patients. HIVBr18 elicited broad, polyfunctional, and durable CD4

Although several studies demonstrate that stressful situations, such as sleep disturbances, negatively impact the innate and adaptive arms of the immune system, their influence on invariant Natural Killer T (iNKT) cells remains unclear. iNKT cells are CD1d-restricted innate T cells that recognize glycolipid antigens and rapidly produce polarizing cytokines being key players in several immune responses, and a potential target for immunotherapy. iNKT cells differ in several aspects from conventional T lymphocytes, including a unique dependence on CD1d-expressing double-positive (DP) thymocytes for intrathymic maturation. As a consequence of stress, DP thymocytes undergo glucocorticoid-induced apoptosis, which might compromise iNKT developmental pathway. Therefore, we used a paradoxical sleep deprivation (SD) model to determine the impact of sleep disturbance on iNKT cell biology. After 72 h of SD, C57Bl/6 mice exhibited a significant increase in systemic glucocorticoid levels and thymus atrophy. Despite marked decrease in the number of DP thymocytes, the ratio CD1d+/CD1d− was higher in SD mice, and the number of thymic iNKT cells remained unaltered, suggesting that SD did not compromise the iNKT developmental pathway. In contrast, SD reduced hepatic IFN-γ, but not, IL-4-producing iNKT cells, without further effect in the spleen. Despite this fact, SD did not affect stimulation of IFN-γ production by iNKT cells, or cytokine release, in response to α-galactosylceramide, a specific antigen. Furthermore, although SD impaired splenic NK cells activity against tumor cells, it did not affect iNKT cell-specific cytotoxicity. Thus, our study shows that SD-induced stress did not impair the iNKT cells’ responses to a cognate antigen.

The 2013-2016 West Africa EBOV epidemic was the biggest EBOV outbreak to date. An analysis of virus-specific CD8+ T-cell immunity in 30 survivors showed that 26 of those individuals had a CD8+ response to at least one EBOV protein. The dominant response (25/26 subjects) was specific to the EBOV nucleocapsid protein (NP). It has been suggested that epitopes on the EBOV NP could form an important part of an effective T-cell vaccine for Ebola Zaire. We show that a 9-amino-acid peptide NP44-52 (YQVNNLEEI) located in a conserved region of EBOV NP provides protection against morbidity and mortality after mouse adapted EBOV challenge. A single vaccination in a C57BL/6 mouse using an adjuvanted microsphere peptide vaccine formulation containing NP44-52 is enough to confer immunity in mice. Our work suggests that a peptide vaccine based on CD8+ T-cell immunity in EBOV survivors is conceptually sound and feasible. Nucleocapsid proteins within SARS-CoV-2 contain multiple class I epitopes with predicted HLA restrictions consistent with broad population coverage. A similar approach to a CTL vaccine design may be possible for that virus.

Although the influence of sleep quality on the immune system is well documented, the mechanisms behind its impact on natural host immunity remain unclear. To evaluate the impact of sleep quality on host immunity against a life-threatening parasitic infection, we used a murine model of rapid eye movement (REM) sleep deprivation (SD) integrated with a model of malaria blood-stage Plasmodium yoelii infection. We demonstrate that sleep disturbance during infection compromises the differentiation of T follicular helper (Tfh) cells, increasing host susceptibility to the parasite. Chemical inhibition of glucocorticoid (Glcs) synthesis during SD showed that abnormal Glcs production compromised the transcription of Tfh-associated genes resulting in impaired germinal center (GC) formation and compromised the humoral response. In summary, our data demonstrate that SD-induced abnormal activation of the hypothalamic-pituitary-adrenal axis drives host susceptibility to infection. Understanding the impact of sleep quality in natural resistance to infection may provide insights for disease management.

Background: Obstructive sleep apnea (OSA) is a chronic sleep disorder and its prevalence is increasing worldwide. This disorder has been consistently associated with a number of comorbidities including cardiovascular diseases, obesity, diabetes and cancer. The relationship between OSA and the immune system is a subject that has attracted an increasing amount of attention, but its underlying mechanisms are not yet completely understood. However, it is clear that OSA severity is associated with inflammation, although the trigger for this phenomenon continues to puzzle scientists. Recently, it has been suggested that hypoxia-induced inflammation could be an important mechanism in this context. Methods: Using data from EPISONO research project, an ongoing epidemiological study of a representative sample of the population of the city of Sao Paulo, we analyzed the immune profile of 461 adults according to OSA severity (mild, moderate and severe) and oxygen saturation. Findings: The results indicate that the hallmark of OSA severity – the apnea-hypopnea index (AHI) – weakly correlates with an inflammatory profile. However, individuals who experience lower oxygen saturation are more likely to exhibit higher total leukocyte and neutrophils counts, a higher neutrophil-lymphocyte ratio (NLR), and an increased concentration of C reactive protein. Interpretation: Thus, our data indicated that oxygen saturation might be a better predictor of inflammation than the apnea-hypopnea index (AHI) and an important prognosis for inflammatory diseases. Funding Statement: ERF, GNP, ST and MLA were supported by grants from Associacao Fundo de Incentivo a Pesquisa (AFIP). ERF, ST, MLA and DSR received fellowships from CNPq. DSR was supported by FAPESP. Declaration of Interests: The authors declare no conflict of interest and approved the manuscript submission. Ethics Approval Statement: The Ethics Committee of Federal University of Sao Paulo approved the EPISONO study (610514/14).

Summary Although the influence of sleep quality on the immune system is well documented, the mechanisms behind its impact on natural host immunity remain unclear. Meanwhile, it has been suggested that neuroimmune interactions play an important role in this phenomenon. To evaluate the impact of stress-induced sleep disturbance on host immunity, we used a murine model of rapid eye movement sleep deprivation (RSD) integrated with a model of malaria blood-stage infection. We demonstrate that sleep disturbance compromises the differentiation of T follicular helper cells, increasing host susceptibility to the parasite. Chemical inhibition of glucocorticoid (Glcs) synthesis showed that abnormal Glcs production compromised the transcription of Tfh-associated genes resulting in impaired germinal center formation and humoral immune response. Our data demonstrate that RSD-induced abnormal activation of the hypothalamic-pituitary-adrenal axis drives host susceptibility to infection. Understanding the impact of sleep quality in natural resistance to infection may provide insights for disease management., Graphical Abstract, Highlights • REM sleep deprivation (RSD) worsens malaria induced by Plasmodium yoelii infection • RSD decreases germinal center formation and impairs specific antibody production • Exacerbated glucocorticoid production impairs T lymphocyte differentiation • The relationship between sleep and immunity is a target for malaria management, Behavioral Neuroscience; Immunology

One of the most promising vaccine candidates against the erythrocytic forms of malaria is the 19 kDa C-terminal region of the merozoite surface protein 1 (MSP1 19 ). As part of our studies aimed at the development of a Plasmodium vivax malaria vaccine, we characterized the immunogenic properties of a new bacterial recombinant protein containing the P. vivax MSP1 19 and two helper T-cell epitopes, the synthetic universal pan allelic DR epitope (PADRE) and a new internal MSP1 P. vivax epitope (DYDVVYLKPLAGMYK). We found that the recognition of His 6 MSP1 19 -DYDVVYLKPLAGMYK-PADRE was as good as the recognition of His 6 MSP1 19 indicating that the presence of the T-cell epitopes PADRE and DYDVVYLKPLAGMYK did not modify the MSP1 19 epitopes recognized by human IgG. The recombinant protein His 6 MSP1 19 -DYDVVYLKPLAGMYK-PADRE proved to be highly immunogenic in marmosets ( Callithrix jacchus jacchus ) when administered in incomplete Freund's adjuvant. However, when administered in other adjuvant formulations such as Quil A, CpG ODN 2006 or MPL/TDM, antibody titers to MSP1 19 were significantly lower. Among these three adjuvants, Quil A proved to be the most efficient one generating antibody titers significantly higher than the others. These results indicated that under the circumstances evaluated, adjuvants were key for the immunogenicity of the recombinant protein His 6 MSP1 19 -DYDVVYLKPLAGMYK-PADRE.

Malaria remains a major global health problem and cerebral malaria (CM) is one of the most serious complications of this disease. Recent years have seen important advances in our understanding of the pathogenesis of cerebral malaria. Parasite sequestration, a hallmark of this syndrome, is thought to be solely responsible for the pathological process. However, this phenomenon cannot explain all aspects of the pathogenesis of CM. The use of an animal model, Plasmodium berghei ANKA in mice, has allowed the identification of specific pathological components of CM. Although multiple pathways may lead to CM, an important role for CD8 + T cells has been clarified. Other cells, including platelets, and mediators such as cytokines also have an important role. In this review we have focused on the role of T cells, and discuss what remains to be studied to understand the pathways by which these cells mediate CM.