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

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

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

Towards a precise test for malaria diagnosis in the Brazilian Amazon: comparison among field microscopy, a rapid diagnostic test, nested PCR, and a computational expert system based on artificial neural networks

<p>Abstract</p> <p>Background</p> <p>Accurate malaria diagnosis is mandatory for the treatment and management of severe cases. Moreover, individuals with asymptomatic malaria are not usually screened by health care facilities, which further complicates disease control efforts. The present study compared the performances of a malaria rapid diagnosis test (RDT), the thick blood smear method and nested PCR for the diagnosis of symptomatic malaria in the Brazilian Amazon. In addition, an innovative computational approach was tested for the diagnosis of asymptomatic malaria.</p> <p>Methods</p> <p>The study was divided in two parts. For the first part, passive case detection was performed in 311 individuals with malaria-related symptoms from a recently urbanized community in the Brazilian Amazon. A cross-sectional investigation compared the diagnostic performance of the RDT Optimal-IT, nested PCR and light microscopy. The second part of the study involved active case detection of asymptomatic malaria in 380 individuals from riverine communities in Rondônia, Brazil. The performances of microscopy, nested PCR and an expert computational system based on artificial neural networks (MalDANN) using epidemiological data were compared.</p> <p>Results</p> <p>Nested PCR was shown to be the gold standard for diagnosis of both symptomatic and asymptomatic malaria because it detected the major number of cases and presented the maximum specificity. Surprisingly, the RDT was superior to microscopy in the diagnosis of cases with low parasitaemia. Nevertheless, RDT could not discriminate the <it>Plasmodium </it>species in 12 cases of mixed infections (<it>Plasmodium vivax </it>+ <it>Plasmodium falciparum</it>). Moreover, the microscopy presented low performance in the detection of asymptomatic cases (61.25% of correct diagnoses). The MalDANN system using epidemiological data was worse that the light microscopy (56% of correct diagnoses). However, when information regarding plasma levels of interleukin-10 and interferon-gamma were inputted, the MalDANN performance sensibly increased (80% correct diagnoses).</p> <p>Conclusions</p> <p>An RDT for malaria diagnosis may find a promising use in the Brazilian Amazon integrating a rational diagnostic approach. Despite the low performance of the MalDANN test using solely epidemiological data, an approach based on neural networks may be feasible in cases where simpler methods for discriminating individuals below and above threshold cytokine levels are available.</p

Lutzomyia longipalpis Saliva or Salivary Protein LJM19 Protects against Leishmania braziliensis and the Saliva of Its Vector, Lutzomyia intermedia

Leishmaniasis, caused by parasitic protozoa Leishmania, is transmitted by bites of female sand flies that, during blood-feeding, inject humans with parasites and saliva. Sand fly saliva has been investigated as a potential vaccine candidate. It was previously shown that immunization with Lutzomyia longipalpis saliva or salivary proteins protects against cutaneous and visceral leishmaniasis. In the present study, we evaluated if immunization with Lu. longipalpis saliva or DNA plasmid coding for a specific sand fly salivary protein (LJM19) can protect hamsters against L. braziliensis plus another sand fly saliva. Immunization with saliva or LJM19 DNA plasmid induced a mononuclear cell infiltrate which can be a marker of protection. The immune response induced by immunization with these insect molecules was able to protect animals against L. braziliensis infection as shown by the significant reduction in lesion size, parasite load in the ear and draining lymph node. These data show the important role of immune response against sand fly saliva components, suggesting the possibility to develop vaccines using a single component of saliva against Leishmania transmitted by different vectors

Natural Breeding Places for Phlebotomine Sand Flies (Diptera: Psychodidae) in a Semiarid Region of Bahia State, Brazil

Few microhabitats have been previously identified as natural breeding places for phlebotomine sand flies so far, and little is known about the influence of climate variables in their density. The present study was conducted in a dry region with a semiarid climate, where visceral leishmaniasis occurs in humans and dogs. The occurrence of breeding places in specific microhabitats was investigated in soil samples collected from five houses, which were also the location used for sampling of adults. All the microhabitats sampled by our study were identified as natural breeding places due to the occurrence of immature forms of sand flies. On a weekly basis, the number of adult sand flies captured was positively correlated with the mean temperature from preceding weeks. These results, in addition to promoting an advance in the knowledge of sand flies biology, may furnish a tool for optimizing the control of the sand flies, by indicating the most suitable periods and microhabitats for the application of insecticides

Dual effect of Lutzomyia longipalpis saliva on Leishmania braziliensis infection is mediated by distinct saliva-induced cellular recruitment into BALB/c mice ear

Abstract\ud \ud \ud \ud Background\ud \ud Leishmania parasites are transmitted to their vertebrate hosts by infected Phlebotomine sand flies during the blood meal of the flies. Sand fly saliva is known to enhance Leishmania spp. infection, while pre-exposure to saliva protects mice against parasitic infections. In this study, we investigated the initial inflammatory leucocyte composition induced by one or three inocula of salivary gland extract (SGE) from Lutzomyia longipalpis in the presence or absence of Leishmania braziliensis.\ud \ud \ud \ud Results\ud \ud We demonstrated that inoculating SGE once (SGE-1X) or three times (SGE-3X), which represented a co-inoculation or a pre-exposure to saliva, respectively, resulted in different cellular infiltrate profiles. Whereas SGE-1X led to the recruitment of all leucocytes subtypes including CD4+ T cells, CD4+CD25+ T cells, dendritic cells, macrophages and neutrophils, the immune cell profile in the SGE-3X group differed dramatically, as CD4+ T cells, CD4+CD25+ T cells, dendritic cells, macrophages and neutrophils were decreased and CD8+ T cells were increased. The SGE-1X group did not show differences in the ear lesion size; however, the SGE-1X group harbored a higher number of parasites. On the other hand, the SGE-3X group demonstrated a protective effect against parasitic disease, as the parasite burden was lower even in the earlier stages of the infection, a period in which the SGE-1X group presented with larger and more severe lesions. These effects were also reflected in the cytokine profiles of both groups. Whereas the SGE-1X group presented with a substantial increase in IL-10 production, the SGE-3X group showed an increase in IFN-γ production in the draining lymph nodes. Analysis of the inflammatory cell populations present within the ear lesions, the SGE-1X group showed an increase in CD4+FOXP3+ cells, whereas the CD4+FOXP3+ population was reduced in the SGE-3X group. Moreover, CD4+ T cells and CD8+ T cells producing IFN-γ were highly detected in the ears of the SGE-3X mice prior to infection. In addition, upon treatment of SGE-3X mice with anti-IFN-γ monoclonal antibody, we observed a decrease in the protective effect of SGE-3X against L. braziliensis infection.\ud \ud \ud \ud Conclusions\ud \ud These results indicate that different inocula of Lutzomyia longipalpis salivary gland extract can markedly modify the cellular immune response, which is reflected in the pattern of susceptibility or resistance to Leishmania braziliensis infection.We are thankful to FAPESP, CAPES, CNPq, INCTV and FAEPA for their financial support