Inmunología en el diagnóstico, patogénesis, tratamiento y prevención por las vacunas contra el COVID-19

A pandemia de covid-19 causada pelo SARS-CoV-2 destacou os riscos cada vez mais frequentes das mudanças significativas na Terra. Tanto o aquecimento global, por alterar os ecossistemas, quanto o aumento da mobilidade, promovendo o contato rápido e regular entre as populações em diferentes regiões, estão implicados no surgimento de surtos epidêmicos e pandemias. Ao longo deste evento, a ciência desempenhou um papel proeminente, evidente em vários campos. A biologia promoveu o rápido conhecimento sobre o SARS-CoV-2 e a epidemiologia, ao estudar os padrões de transmissão do vírus e na disseminação da infecção. A matemática e a física contribuíram para a elaboração de modelos para prever a evolução da doença e o impacto das medidas não farmacológicas de contenção, e.g. Em múltiplas especialidades, as ciências da saúde como medicina, fisioterapia e enfermagem também estiveram em evidência. Neste texto, destacamos a contribuição da imunologia por meio de seu papel no campo do diagnóstico, na compreensão dos mecanismos da doença, que levam a métodos de tratamento mais eficazes, e no desenvolvimento de vacinas capazes de proteger contra o mencionado vírus.The COVID-19 pandemic, caused by SARS-CoV-2, highlighted the risks, more and more frequently, from the significant changes on Earth. Global warming, which alters ecosystems, and increased mobility by promoting rapid and regular contact between populations in different regions, are implicated in the emergence of epidemic outbreaks and pandemics. Throughout the COVID-19 pandemic, science played a prominent role. The role of science has been very much in evidence in several fields. In biology, it promoted the rapid knowledge of SARS-CoV-2, in epidemiology, by studying patterns of virus transmission and spread of infection. Mathematics and physics contributed to the elaboration of models to predict the evolution of the disease and the impact of non-pharmacological measures of containment, e.g. In multiple specialties, the health sciences such as medicine, physiotherapy, and nursing, among others, were in evidence. In this text, we highlight the contribution of immunology through its role in the fields of diagnosis, understanding the mechanisms of disease, which lead to more efficient treatment methods, and the development of vaccines capable of protecting against COVID-19.La pandemia de COVID-19, causada por el SARS-CoV-2, puso de relieve los riesgos, cada vez más frecuentes, de los cambios significativos en la Tierra. Tanto el calentamiento global, al alterar los ecosistemas, como el aumento de la movilidad, promoviendo un contacto rápido y regular entre poblaciones de diferentes regiones, están implicados en la aparición de brotes epidémicos y pandemias. Durante la pandemia de COVID-19, la ciencia jugó un papel destacado en varios campos. La biología permitió el rápido conocimiento del SARS-CoV-2 y la epidemiología el estudio de los patrones de transmisión de virus y propagación de la infección. Las matemáticas y la física aportaron la elaboración de modelos para predecir la evolución de la enfermedad y el impacto de las medidas de contención no farmacológicas, e. g. Las múltiples especialidades de las ciencias de la salud, como la medicina, la fisioterapia, o la enfermería, entre otras, también desempeñaron un papel evidente. En este texto, destacamos la contribución de la inmunología a través de su papel en los campos del diagnóstico, la comprensión de los mecanismos de la enfermedad, que conducen a métodos de tratamiento más eficientes, y el desarrollo de vacunas capaces de proteger contra el COVID-19

New Insights on the Inflammatory Role of Lutzomyia longipalpis Saliva in Leishmaniasis

When an haematophagous sand fly vector insect bites a vertebrate host, it introduces its mouthparts into the skin and lacerates blood vessels, forming a hemorrhagic pool which constitutes an intricate environment of cell interactions. In this scenario, the initial performance of host, parasite, and vector “authors” will heavily influence the course of Leishmania infection. Recent advances in vector-parasite-host interaction have elucidated “co-authors” and “new roles” not yet described. We review here the stimulatory role of Lutzomyia longipalpis saliva leading to inflammation and try to connect them in an early context of Leishmania infection

Severe Plasmodium vivax malaria exhibits marked inflammatory imbalance

<p>Abstract</p> <p>Background</p> <p>Despite clinical descriptions of severe vivax malaria cases having been reported, data regarding immunological and inflammatory patterns are scarce. In this report, the inflammatory and immunological status of both mild and severe vivax malaria cases are compared in order to explore immunopathological events in this disease.</p> <p>Methods and Results</p> <p>Active and passive malaria case detections were performed during 2007 in Buritis, Rondônia, in the Brazilian Amazon. A total of 219 participants enrolled the study. Study individuals were classified according to the presence of <it>Plasmodium vivax </it>infection within four groups: non-infected (n = 90), asymptomatic (n = 60), mild (n = 50) and severe vivax infection (n = 19). A diagnosis of malaria was made by microscopy and molecular assays. Since at present no clear criteria define severe vivax malaria, this study adapted the consensual criteria from falciparum malaria. Patients with severe <it>P. vivax </it>infection were younger, had lived for shorter time in the endemic area, and recalled having experienced less previous malaria episodes than individuals with no malaria infection and with mild or asymptomatic infection. Strong linear trends were identified regarding increasing plasma levels of C reactive protein (CRP), serum creatinine, bilirubins and the graduation of disease severity. Plasma levels of tumour necrosis factor (TNF), interferon-gamma(IFN-gamma) and also IFN-gamma/interleukin-10 ratios were increased and exhibited a linear trend with gradual augmentation of disease severity. Both laboratory parameters of organ dysfunction and inflammatory cytokines were reduced during anti-parasite therapy in those patients with severe disease.</p> <p>Conclusion</p> <p>Different clinical presentations of vivax malaria infection present strong association with activation of pro-inflammatory responses and cytokine imbalance. These findings are of utmost importance to improve current knowledge about physiopathological concepts of this serious widespread disease.</p

BALB/c Mice Vaccinated with Leishmania major Ribosomal Proteins Extracts Combined with CpG Oligodeoxynucleotides Become Resistant to Disease Caused by a Secondary Parasite Challenge

Leishmaniasis is an increasing public health problem and effective vaccines are not currently available. We have previously demonstrated that vaccination with ribosomal proteins extracts administered in combination of CpG oligodeoxynucleotides protects susceptible BALB/c mice against primary Leishmania major infection. Here, we evaluate the long-term immunity to secondary infection conferred by this vaccine. We show that vaccinated and infected BALB/c mice were able to control a secondary Leishmania major challenge, since no inflammation and very low number of parasites were observed in the site of reinfection. In addition, although an increment in the parasite burden was observed in the draining lymph nodes of the primary site of infection we did not detected inflammatory lesions at that site. Resistance against reinfection correlated to a predominant Th1 response against parasite antigens. Thus, cell cultures established from spleens and the draining lymph node of the secondary site of infection produced high levels of parasite specific IFN-γ in the absence of IL-4 and IL-10 cytokine production. In addition, reinfected mice showed a high IgG2a/IgG1 ratio for anti-Leishmania antibodies. Our results suggest that ribosomal vaccine, which prevents pathology in a primary challenge, in combination with parasite persistence might be effective for long-term maintenance of immunity

Anti-Anopheles darlingi saliva antibodies as marker of Plasmodium vivax infection and clinical immunity in the Brazilian Amazon

<p>Abstract</p> <p>Background</p> <p>Despite governmental and private efforts on providing malaria control, this disease continues to be a major health threat. Thus, innovative strategies are needed to reduce disease burden. The malaria vectors, through the injection of saliva into the host skin, play important role on disease transmission and may influence malaria morbidity. This study describes the humoral immune response against <it>Anopheles (An.) darlingi </it>saliva in volunteers from the Brazilian Amazon and addresses the association between levels of specific antibodies and clinical presentation of <it>Plasmodium (P.) vivax </it>infection.</p> <p>Methods</p> <p>Adult volunteers from communities in the Rondônia State, Brazil, were screened in order to assess the presence of <it>P. vivax </it>infection by light microscopy and nested PCR. Non-infected volunteers and individuals with symptomatic or symptomless infection were randomly selected and plasma collected. <it>An. darlingi </it>salivary gland sonicates (SGS) were prepared and used to measure anti-saliva antibody levels. Plasma interleukin (IL)-10 and interferon (IFN)-γ levels were also estimated and correlated to anti-SGS levels.</p> <p>Results</p> <p>Individuals infected with <it>P. vivax </it>presented higher levels of anti-SGS than non-infected individuals and antibody levels could discriminate infection. Furthermore, anti-saliva antibody measurement was also useful to distinguish asymptomatic infection from non-infection, with a high likelihood ratio. Interestingly, individuals with asymptomatic parasitaemia presented higher titers of anti-SGS and lower IFN-γ/IL-10 ratio than symptomatic ones. In <it>P. vivax</it>-infected asymptomatic individuals, the IFN-γ/IL-10 ratio was inversely correlated to anti-SGS titers, although not for while in symptomatic volunteers.</p> <p>Conclusion</p> <p>The estimation of anti-<it>An. darlingi </it>antibody levels can indicate the probable <it>P. vivax </it>infection status and also could serve as a marker of disease severity in this region of Brazilian Amazon.</p

Arginase levels and their association with Th17-related cytokines, soluble adhesion molecules (sICAM-1 and sVCAM-1) and hemolysis markers among steady-state sickle cell anemia patients

Sickle cell anemia (SCA) is characterized by a marked endothelial dysfunction, owing to many factors. Arginine metabolism can be related to the inflammatory chronic state presented by patients, playing a key role in their clinical outcome and vascular endothelium. We investigated the serum arginase levels in 50 SCA patients (22 men and 28 women, mean age of 17 ± 10.5 years) and 28 healthy controls. Serum arginase levels were associated with biochemical hemolysis markers and cytokines involved in Th17 response, as well as levels of soluble intercellular adhesion molecule-1 (sICAM-1) and vascular cell adhesion molecule-1 (sVCAM-1). Arginase concentrations were higher in SCA patients, compared with controls (p = 0.005), and were significantly and positively associated with total bilirubin (p = 0.004), indirect bilirubin (p = 0.04), and aspartate aminotransferase (AST; p = 0.039) in the SCA patient group. Moreover, arginase was significantly and positively associated with transforming growth factor-beta (TGF-beta; p = 0.008) among SCA patients. sICAM-1 was significantly and positively associated to reticulocytes (p = 0.014) and AST (p = 0.04). sVCAM-1 was likewise associated with lactate dehydrogenase (p = 0.03). These data suggest a new insight into arginase metabolism, as we show here a shift in arginine catabolism, where TGF-beta may induces the arginase pathway instead of the nitric oxide pathway and a possible involvement of the vascular activation and the serum arginase in chronic hemolysis among SCA patients. Additional studies should be carried out in order to investigate the mechanisms by which TGF-beta participates in the metabolism of arginase in SCA patients

Personal data usage and privacy considerations in the COVID-19 global pandemic

Data has become increasingly important and valuable for both scientists and health authorities searching for answers to the COVID-19 crisis. Due to difficulties in diagnosing this infection in populations around the world, initiatives supported by digital technologies are being developed by governments and private companies to enable the tracking of the public’s symptoms, contacts and movements. Considering the current scenario, initiatives designed to support infection surveillance and monitoring are essential and necessary. Nonetheless, ethical, legal and technical questions abound regarding the amount and types of personal data being collected, processed, shared and used in the name of public health, as well as the concomitant or posterior use of this data. These challenges demonstrate the need for new models of responsible and transparent data and technology governance in efforts to control SARS-COV2, as well as in future public health emergencies

Leishmania major Ribosomal Proteins Extracts Combined with CpG Oligodeoxynucleotides Become Resistant to Disease Caused by a Secondary Parasite Challenge

Leishmaniasis is an increasing public health problem and effective vaccines are not currently available. We have previously demonstrated that vaccination with ribosomal proteins extracts administered in combination of CpG oligodeoxynucleotides protects susceptible BALB/c mice against primary Leishmania major infection. Here, we evaluate the long-term immunity to secondary infection conferred by this vaccine. We show that vaccinated and infected BALB/c mice were able to control a secondary Leishmania major challenge, since no inflammation and very low number of parasites were observed in the site of reinfection. In addition, although an increment in the parasite burden was observed in the draining lymph nodes of the primary site of infection we did not detected inflammatory lesions at that site. Resistance against reinfection correlated to a predominant Th1 response against parasite antigens. Thus, cell cultures established from spleens and the draining lymph node of the secondary site of infection produced high levels of parasite specific IFN-γ in the absence of IL-4 and IL-10 cytokine production. In addition, reinfected mice showed a high IgG2a/IgG1 ratio for anti-Leishmania antibodies. Our results suggest that ribosomal vaccine, which prevents pathology in a primary challenge, in combination with parasite persistence might be effective for long term maintenance of immunity

Towards development of novel immunization strategies against leishmaniasis using PLGA nanoparticles loaded with kinetoplastid membrane protein-11

Background: Vaccine development has been a priority in the fight against leishmaniases, which are vector-borne diseases caused by Leishmania protozoa. Among the different immunization strategies employed to date is inoculation of plasmid DNA coding for parasite antigens, which has a demonstrated ability to induce humoral and cellular immune responses. In this sense, inoculation of plasmid DNA encoding Leishmania kinetoplasmid membrane protein-11 (KMP-11) was able to confer protection against visceral leishmaniasis. However, recently the use of antigen delivery systems such as poly(lactic-co-glycolic acid) (PLGA) nanoparticles has also proven effective for eliciting protective immune responses. Methods: In the present work, we tested two immunization strategies with the goal of obtaining protection, in terms of lesion development and parasite load, against cutaneous leishmaniasis caused by L. braziliensis. One strategy involved immunization with plasmid DNA encoding L. infantum chagasi KMP-11. Alternatively, mice were primed with PLGA nanoparticles loaded with the recombinant plasmid DNA and boosted using PLGA nanoparticles loaded with recombinant KMP-11. Results: Both immunization strategies elicited detectable cellular immune responses with the presence of both proinflammatory and anti-inflammatory cytokines; mice receiving the recombinant PLGA nanoparticle formulations also demonstrated anti-KMP-11 IgG1 and IgG2a. Mice were then challenged with L. braziliensis, in the presence of sand fly saliva. Lesion development was not inhibited following either immunization strategy. However, immunization with PLGA nanoparticles resulted in a more prominent reduction in parasite load at the infection site when compared with immunization using plasmid DNA alone. This effect was associated with a local increase in interferon-gamma and in tumor necrosis factor-alpha. Both immunization strategies also resulted in a lower parasite load in the draining lymph nodes, albeit not significantly. Conclusion: Our results encourage the pursuit of immunization strategies employing nanobased delivery systems for vaccine development against cutaneous leishmaniasis caused by L. braziliensis infection. © 2012 Santos et al, publisher and licensee Dove Medical Press Ltd.Government of Navarra; CAN Foundation and CYTEDPeer Reviewe