- Brucella: diagnosis, epidemiology, treatment
- Escherichia coli research studies
- SARS-CoV-2 and COVID-19 Research
- Immunotherapy and Immune Responses
- vaccines and immunoinformatics approaches
- Monoclonal and Polyclonal Antibodies Research
- Galectins and Cancer Biology
- Viral gastroenteritis research and epidemiology
- Hepatitis B Virus Studies
- Trypanosoma species research and implications
- COVID-19 Clinical Research Studies
- SARS-CoV-2 detection and testing
- Animal Virus Infections Studies
- Biochemical and Molecular Research
- CAR-T cell therapy research
- Herpesvirus Infections and Treatments
- Mosquito-borne diseases and control
- Cytokine Signaling Pathways and Interactions
- Toxoplasma gondii Research Studies
- Atherosclerosis and Cardiovascular Diseases
- Signaling Pathways in Disease
- Immune cells in cancer
- Bacterial biofilms and quorum sensing
- Salmonella and Campylobacter epidemiology
- Burkholderia infections and melioidosis
Consejo Nacional de Investigaciones Científicas y Técnicas
2016-2025
National University of General San Martín
2015-2025
Universidad Nacional de San Martín
2025
Instituto Tecnológico de Chascomús
2015-2017
Hospital de Clínicas "José de San Martín"
2008-2013
University of Buenos Aires
2008-2013
Institute of Astronomy and Space Physics
2013
Universidad Nacional del Centro de la Provincia de Buenos Aires
2009
ABSTRACT Available vaccines against Brucella spp. are live attenuated strains. In order to engineer a better vaccine be used in animals and humans, our laboratory aims develop an innocuous subunit vaccine. Particularly, we interested the outer membrane proteins (OMPs) of B. abortus : Omp16 Omp19. this study, assessed use these as BALB/c mice. Immunization with lipidated (L-Omp16) or L-Omp19 incomplete Freund's adjuvant (IFA) conferred significant protection infection. Vaccination unlipidated...
As Brucella infections occur mainly through mucosal surfaces, the development of administered vaccines could be radical for control brucellosis. In this work we evaluated potential abortus 19 kDa outer membrane protein (U-Omp19) as an edible subunit vaccine against We investigated protective immune response elicited oral B. infection after vaccination mice with leaves from transgenic plants expressing U-Omp19; or plant-made E. coli-made purified U-Omp19. All tested U-Omp19 formulations...
Knowing the inherent stimulatory properties of lipid moiety bacterial lipoproteins, we first hypothesized that Brucella abortus outer membrane protein (Omp)16 lipoprotein would be able to elicit a protective immune response without need external adjuvants. In this study, demonstrate Omp16 administered by i.p. route confers significant protection against B. infection and evoked is independent lipidation. To date, requirement adjuvants induce similar levels control live vaccine S19. Moreover,...
Abstract In the context of continuous emergence SARS-CoV-2 variants concern (VOCs), one strategy to prevent severe outcomes COVID-19 is developing safe and effective broad-spectrum vaccines. Here, we present preclinical studies a RBD vaccine derived from Gamma variant adjuvanted with Alum. The Gamma-adapted more immunogenic than Ancestral in terms inducing broader neutralizing antibodies. presents B-cell restricted epitopes induces higher proportion specific-B cells plasmablasts version....
Salmonella enterica serovar Typhimurium causes acute diarrhea upon oral infection in humans. The harsh and proteolytic environment found the gastrointestinal tract is first obstacle that these bacteria face after infection. However, mechanisms allow to survive hostile conditions of gut are poorly understood. ecotin gene an extensive range known phyla it encodes a protein has been shown inhibit serine proteases. Thus, present work we studied role host-pathogen interactions. We ∆ strain...
Aberrant Stat3 activation and signaling contribute to malignant transformation by promoting cell cycle progression, inhibiting apoptosis, mediating tumor immune evasion. inhibition in cells induces the expression of chemokines proinflammatory cytokines, so we proposed apply Stat3-inhibited breast cancer as a source immunogens induce an antitumor response. Studies were performed two murine models which is activated: progestin-dependent C4HD 4T1 cells. We immunized BALB/c mice with irradiated...
In this work, we evaluated recombinant receptor binding domain (RBD)-based vaccine formulation prototypes with potential for further clinical development. We assessed different formulations containing RBD plus alum, AddaS03, AddaVax, or the combination of alum and U-Omp19: a novel Brucella spp. protease inhibitor adjuvant. Results show that composed U-Omp19 as adjuvants has better performance: it significantly increased mucosal systemic neutralizing antibodies in comparison to antigen...
A Gamma Variant RBD-based aluminum hydroxide adjuvanted vaccine called ARVAC CG was selected for a first in human clinical trial. Healthy male and female participants (18-55 years old) with complete COVID-19-primary scheme were assigned to receive two intramuscular doses of either low-dose or high-dose CG. The primary endpoint safety. secondary objective humoral immunogenicity. Cellular immune responses studied as an exploratory objective. trial prospectively registered PRIISA.BA...
Abstract Background Central nervous system (CNS) invasion by bacteria of the genus Brucella results in an inflammatory disorder called neurobrucellosis. We have recently demonstrated that B. abortus infects microglia and astrocytes, eliciting production a variety pro-inflammatory cytokines which contribute to CNS damage. Matrix metalloproteinases (MMP) been implicated tissue destruction range pathological situations CNS. Increased MMP secretion is induced diseases characterized...
Abstract In this study, we demonstrate that the unlipidated (U) outer membrane protein (Omp) 19 from Brucella spp. is a competitive inhibitor of human cathepsin L. U-Omp19 inhibits lysosome cathepsins and APC-derived microsome activity in vitro partially lysosomal L within live APCs. Codelivery with Ag can reduce intracellular digestion increases half-life dendritic cells (DCs). retains Lamp-2+ compartments after its internalization promotes sustained expression MHC class I/peptide complexes...
Trypanosoma brucei are protozoan parasites that cause sleeping sickness in humans and nagana cattle. Inside the mammalian host, a quorum sensing-like mechanism coordinates its differentiation from slender replicative form into quiescent stumpy form, limiting growth activating metabolic pathways beneficial to parasite insect host. The post-translational modification of proteins with Small Ubiquitin-like MOdifier (SUMO) enables dynamic regulation cellular metabolism. SUMO can be conjugated...
We report here that a bacterial protease inhibitor from Brucella spp. called U-Omp19 behaves as an ideal constituent for vaccine formulation against infectious diseases. When co-administered orally with antigen (Ag), U-Omp19: i) can bypass the harsh environment of gastrointestinal tract by inhibiting stomach and intestine proteases consequently increases half-life Ag at immune inductive sites: Peyer's patches mesenteric lymph nodes while ii) it induces recruitment activation presenting cells...
Most pathogens infect through mucosal surfaces and parenteral immunization typically fails to induce effective immune responses at these sites. Development of oral administered vaccines capable inducing as well systemic immunity while bypassing the issues antigen degradation tolerance could be crucial for control enteropathogens. This study, demonstrates that U-Omp19, a bacterial protease inhibitor with immunostimulatory features, co-administered Salmonella antigens by route, enhances in...
Pathogenic microorganisms confront several proteolytic events in the molecular interplay with their host, highlighting that proteolysis and its regulation play an important role during infection. Microbial inhibitors, along target endogenous/exogenous enzymes, may directly affect host's defense mechanisms promote Omp19 is a Brucella spp. conserved lipoprotein anchored by lipid portion outer membrane. Previous work demonstrated purified unlipidated (U-Omp19) has protease inhibitor activity...
The discovery of novel mucosal adjuvants will help to develop new formulations control infectious and allergic diseases. In this work we demonstrate that U-Omp16 from Brucella spp. delivered by the nasal route (i.n.) induced an inflammatory immune response in bronchoalveolar lavage (BAL) lung tissues. Nasal co-administration with model antigen (Ag) ovalbumin (OVA) increased amount Ag tissues OVA-specific systemic IgG T helper (Th) 1 responses. usefulness was also assessed a mouse food...
The study of capture and processing antigens (Ags) by intestinal epithelial cells is very important for development new oral administration systems. Efficient Ag delivery systems must resist enzymatic degradation gastric proteases deliver the across biological barriers. recombinant unlipidated outer membrane protein from Brucella spp. (U-Omp19) a protease inhibitor with immunostimulatory properties used as adjuvant in vaccine formulations. In present work we further characterized its...
SUMMARY Background In view of the emergence SARS-CoV-2 immune escape variants and evidence waning immunity, new immunisation strategies variant-adapted vaccines are needed. Based on preclinical proof concept studies requirement booster vaccines, Gamma Variant RBD-based ARVAC-CG vaccine was selected for a first clinical trial in humans. Methods Eighty participants (healthy adults, 18-55 years-old) were sequentially assigned to receive two (28 days apart) intramuscular doses 25-μg (n=60) or...
Abstract The COVID-19 pandemic continues with the emergence of successive new variants concern (VOC). One strategy to prevent breakthrough infections is developing safe and effective broad-spectrum vaccines. Here, we present preclinical studies a RBD recombinant vaccine candidate derived from Gamma SARS-CoV-2 variant adjuvanted alum. RBD-derived antigen elicited better neutralizing antibody T cell responses than formulation containing ancestral antigen. Gamma-adapted subunit long-lasting...
Abstract Background This study (ARVAC-F2-3-002) assessed the immunogenicity, safety, and tolerability of a recombinant booster vaccine (ARVAC) containing receptor binding domain SARS-CoV-2 Spike protein in three different versions: Gamma (ARVACGamma), Omicron BA.4/5 (ARVACOmicron), Gamma/Omicron Bivalent (ARVACBivalent). Methods Randomized, double-blind, crossover, placebo-controlled, multicenter (11 centers Argentina) Phase II/III trial including adult volunteers previously vaccinated...