Alexandre V. Machado

ORCID: 0000-0003-1506-4093
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About
Contact & Profiles
Research Areas
  • Influenza Virus Research Studies
  • Trypanosoma species research and implications
  • Research on Leishmaniasis Studies
  • Respiratory viral infections research
  • SARS-CoV-2 and COVID-19 Research
  • Immune Cell Function and Interaction
  • Immune Response and Inflammation
  • Pneumonia and Respiratory Infections
  • COVID-19 Clinical Research Studies
  • interferon and immune responses
  • Parasitic Infections and Diagnostics
  • Animal Disease Management and Epidemiology
  • Viral gastroenteritis research and epidemiology
  • Mosquito-borne diseases and control
  • Virus-based gene therapy research
  • Immunotherapy and Immune Responses
  • Toxoplasma gondii Research Studies
  • Primate Behavior and Ecology
  • Cytomegalovirus and herpesvirus research
  • vaccines and immunoinformatics approaches
  • Vaccine Coverage and Hesitancy
  • Malaria Research and Control
  • Neutropenia and Cancer Infections
  • HIV/AIDS oral health manifestations
  • Insect symbiosis and bacterial influences

Fundação Oswaldo Cruz
2016-2025

Universidade Federal de Minas Gerais
2004-2024

ORCID
2024

Instituto Butantan
2019

Universidade Nove de Julho
2019

Universidade São Judas Tadeu
2019

Centre National de la Recherche Scientifique
2003-2005

Institut Pasteur
2003-2005

ABSTRACT A heterologous prime-boost strategy using plasmid DNA, followed by replication-defective recombinant adenovirus 5, is being proposed as a powerful way to elicit CD4 + and CD8 T-cell-mediated protective immunity against intracellular pathogens. We confirmed this concept furthered existing research providing evidence that the regimen gene encoding amastigote surface protein 2 elicited (reduction of acute parasitemia prolonged survival) experimental infection with Trypanosoma cruzi ....

10.1128/iai.01459-08 article EN Infection and Immunity 2009-08-04

Influenza virus A (IAV) causes annual epidemics and intermittent pandemics that affect millions of people worldwide. Potent inflammatory responses are commonly associated with severe cases IAV infection. The complement system, an important mechanism innate humoral immune to infections, is activated during primary infection mediates, in association natural IgM, viral neutralization by virion aggregation coating hemmagglutinin. Increased levels the anaphylatoxin C5a were found patients fatally...

10.1371/journal.pone.0064443 article EN cc-by PLoS ONE 2013-05-16

Chagas disease (CD), caused by the protozoan Trypanosoma cruzi, is a prototypical neglected tropical disease. Specific immunity promotes acute phase survival. Nevertheless, one-third of CD patients develop chronic chagasic cardiomyopathy (CCC) associated with parasite persistence and immunological unbalance. Currently, therapeutic management only mitigates CCC symptoms. Therefore, vaccine arises as an alternative to stimulate protective thereby prevent, delay progression even reverse CCC. We...

10.1371/journal.ppat.1004594 article EN cc-by PLoS Pathogens 2015-01-24

Protection against protozoan parasite Trypanosoma cruzi has been shown to be dependent on the induction of type 1 immune responses. Replication-deficient human 5 recombinant adenoviruses have an unsurpassed ability induce Thus, we constructed two encoding antigens trans-sialidase (rAdTS) and amastigote surface protein-2 (rAdASP2). Both were genetically engineered secrete products in order both optimal antibody T cell Immunizations mice with rAdASP2 rAdTS induced high levels serum antibodies...

10.1089/hum.2006.17.898 article EN Human Gene Therapy 2006-09-01

Abstract Interference or competition between CD8+ T cells restricted by distinct MHC-I molecules can be a powerful means to establish an immunodominant response. However, its importance during infections is still questionable. In this study, we describe that following infection of mice with the human pathogen Trypanosoma cruzi, cell immune response developed directed H-2Kb-restricted epitope expressed members trans-sialidase family surface proteins. To determine whether immunodominance was...

10.4049/jimmunol.180.3.1737 article EN The Journal of Immunology 2008-02-01

Influenza A virus causes annual epidemics which affect millions of people worldwide. recent pandemic brought new awareness over the health impact disease. It is thought that a severe inflammatory response against contributes to disease severity and death. Therefore, modulating effects mediators may represent therapy infection. Platelet activating factor (PAF) receptor (PAFR) deficient mice were used evaluate role gene in model experimental infection with A/WSN/33 H1N1 or reassortant H3N1...

10.1371/journal.ppat.1001171 article EN cc-by PLoS Pathogens 2010-11-04

MHC class Ia-restricted CD8(+) T cells are important mediators of the adaptive immune response against infections caused by intracellular microorganisms. Whereas antigen-specific effector can clear infection pathogens, in some circumstances, is suboptimal and microorganisms survive, causing host death or chronic infection. Here, we explored cellular molecular mechanisms that could explain why cell-mediated immunity during with human protozoan parasite Trypanosoma cruzi not optimal. For...

10.1371/journal.ppat.1002699 article EN cc-by PLoS Pathogens 2012-05-17

Rationale: Influenza A infections are a leading cause of morbidity and mortality worldwide especially when associated with secondary pneumococcal infections. Inflammation is important to control pathogen proliferation but may also tissue injury death. CXCR1/2 chemokine receptors relevant for the recruitment neutrophils. We investigated role during influenza, post-influenza Methods: Mice were infected influenza virus (IAV) or Streptococcus pneumoniae then treated daily antagonist DF2162. To...

10.3389/fimmu.2017.01799 article EN cc-by Frontiers in Immunology 2017-12-12

Abstract Both T cells and B have been shown to be generated after infection with SARS-CoV-2 yet protocols or experimental models study one the other are less common. Here, we generate a chimeric protein (SpiN) that comprises receptor binding domain (RBD) from Spike (S) nucleocapsid (N) antigens SARS-CoV-2. Memory CD4 + CD8 specific for SpiN could detected in blood of both individuals vaccinated Coronavac vaccine COVID-19 convalescent donors. In mice, elicited strong IFN-γ response by high...

10.1038/s41467-022-32547-y article EN cc-by Nature Communications 2022-08-17

Protective immunity against lethal infection is developed when BALB/c or C57BL/6 mice are immunized with plasmids containing genes from the protozoan parasite Trypanosoma cruzi. However, genetic vaccination of highly susceptible mouse strain A/Sn promoted limited survival after challenge. This observation questioned whether this type would be appropriate for individuals. Here, we compared protective efficacy and immune response individual combined encoding trans-sialidase (TS) amastigote...

10.1089/hum.2004.15.878 article EN Human Gene Therapy 2004-09-01

Recently, we described a heterologous prime-boost strategy using plasmid DNA followed by replication-defective human recombinant adenovirus type 5 as powerful to elicit long-lived CD8(+) T-cell-mediated protective immunity against experimental systemic infection of mice with intracellular protozoan parasite, Trypanosoma cruzi. In the present study, further characterized T cells. We compared several functional and phenotypic aspects specific cells 14 or 98 days after last immunizing dose...

10.1128/iai.01190-10 article EN cc-by Infection and Immunity 2011-03-01

During adaptive immune response, pathogen-specific CD8+ T cells recognize preferentially a small number of epitopes, phenomenon known as immunodominance. Its biological implications during natural or vaccine-induced responses are still unclear. Earlier, we have shown that experimental infection, the human intracellular pathogen Trypanosoma cruzi restricts repertoire generating strong We hypothesized this could be mechanism used by parasite to reduce breath and magnitude favoring parasitism,...

10.1371/journal.pone.0022011 article EN cc-by PLoS ONE 2011-07-14

The current COVID-19 vaccines protect against severe disease, but are not effective in controlling replication of the Variants Concern (VOCs). Here, we used existing pre-clinical models and moderate to evaluate efficacy a Spike-based DNA vaccine (pCTV-WS) for protection different VOCs. Immunization transgenic (K18-hACE2) mice hamsters induced significant levels neutralizing antibodies (nAbs) Wuhan Delta isolates, Gamma Omicron variants. Nevertheless, pCTV-WS offered all Consistently, lung...

10.1038/s41541-023-00616-y article EN cc-by npj Vaccines 2023-02-13

In this work, we explored an original vaccination protocol using recombinant influenza and adenovirus. We constructed viruses harboring dicistronic NA segments containing the surface antigen 2 (SAG2) from Toxoplasma gondii under control of duplicated 3' promoter. Recombinant were able to drive expression foreign SAG2 sequence in cell culture replicate efficiently both lungs infected mice. addition, mice primed with virus boosted a adenovirus encoding elicited humoral cellular immune...

10.1016/j.vaccine.2010.02.003 article EN publisher-specific-oa Vaccine 2010-02-27

Influenza A virus (IAV) infects millions of people annually and predisposes to secondary bacterial infections. Inhalation fungi within the Cryptococcus complex causes pulmonary disease with meningo-encephalitis. Underlying is a strong risk factor for development C. gattii cryptococcosis though effect concurrent infection IAV has not been studied. We developed an in vivo model H1N1 coinfection. Coinfection resulted major increase morbidity mortality, severe lung damage high brain fungal...

10.3389/fcimb.2017.00419 article EN cc-by Frontiers in Cellular and Infection Microbiology 2017-09-26

Immunisation with Amastigote Surface Protein 2 (asp-2) and trans-sialidase (ts) genes induces protective immunity in highly susceptible A/Sn mice, against infection parasites of the Y strain Trypanosoma cruzi. Based on immunological biological variations T. cruzi parasites, our goal was to validate vaccination results using different parasite strains. Due importance CD8+ T cells immunity, we initially determined which strains expressed immunodominant H-2Kk-restricted epitope TEWETGQI. We...

10.1016/j.vaccine.2009.07.013 article EN publisher-specific-oa Vaccine 2009-07-26

Inflammation triggered by influenza A virus (IAV) infection is important for viral clearance, induction of adaptive responses, and return to lung homeostasis. However, an exaggerated immune response, characterized the overproduction chemokines, can lead intense injury, contributing mortality. Chemokine scavenger receptors, such as ACKR2, control levels CC chemokines influencing responses. Among chemokine targets CCL5 recruit activate lymphocytes. We investigated role ACKR2 during IAV in...

10.1152/ajplung.00134.2019 article EN AJP Lung Cellular and Molecular Physiology 2020-01-29

In the present study we evaluated protection raised by immunization with recombinant influenza viruses carrying sequences coding for polypeptides corresponding to medial and carboxi-terminal moieties of Trypanosoma cruzi ´s amastigote surface protein 2 (ASP2). Those were used in sequential adenovirus (heterologous prime-boost protocol) encoding complete sequence ASP2 (Ad-ASP2) two mouse strains (C57BL/6 C3H/He). The CD8 effector response elicited this protocol was comparable that observed...

10.1371/journal.pone.0061795 article EN cc-by PLoS ONE 2013-04-24

Heterologous prime-boost vaccination using plasmid DNA followed by replication-defective adenovirus vector generates a large number of specific CD8+ T effector memory (TEM) cells that provide long-term immunity against variety pathogens. In the present study, we initially characterized frequency, phenotype, and function these in vaccinated mice were subjected to infectious challenge with human protozoan parasite Trypanosoma cruzi. We observed frequency spleens increased after challenge....

10.1089/hum.2013.218 article EN Human Gene Therapy 2014-02-25

T-cell mediated immune responses are critical for acquired immunity against infection by the intracellular protozoan parasite Trypanosoma cruzi. Despite its importance, it is currently unknown where protective T cells primed and whether they need to re-circulate in order exert their anti-parasitic effector functions. Here, we show that after subcutaneous challenge, CD11c(+)-dependent specific CD8(+) response immunodominant epitopes arises almost simultaneously draining lymph node (LN)...

10.1016/j.vaccine.2012.02.037 article EN publisher-specific-oa Vaccine 2012-02-28

: Influenza A virus (IAV) infection causes severe pulmonary disease characterized by intense leukocyte infiltration. Phosphoinositide-3 kinases (PI3Ks) are central signaling enzymes, involved in cell growth, survival and migration. Class IB PI3K or PI3Kγ, mainly expressed leukocytes, migration during inflammation. Here, we investigated the contribution of PI3Kγ for inflammatory antiviral responses to IAV. knock out (KO) mice were highly susceptible lethality following with influenza A/WSN/33...

10.3389/fimmu.2018.00975 article EN cc-by Frontiers in Immunology 2018-05-15

The β1i, β2i and β5i immunoproteasome subunits have an important role in defining the repertoire of MHC class I-restricted epitopes. However, impact combined deficiency three development protective immunity to intracellular pathogens has not been investigated. Here, we demonstrate that immunoproteasomes play a key host resistance genetic vaccination-induced protection against human pathogen Trypanosoma cruzi (the causative agent Chagas disease), which is dependent on CD8+ T cells IFN-γ...

10.1371/journal.ppat.1005593 article EN cc-by PLoS Pathogens 2016-04-29
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