Miriam Postan - Academia.edu (original) (raw)
Papers by Miriam Postan
Frontiers in cellular and infection microbiology, Feb 28, 2024
Research Square (Research Square), Apr 28, 2023
Chagas' is a neglected disease caused by the eukaryotic kinetoplastid parasite Trypanosoma cruzi.... more Chagas' is a neglected disease caused by the eukaryotic kinetoplastid parasite Trypanosoma cruzi. Currently there are about 8 million infected people worldwide, most of them at the chronic phase of the disease, which involves cardiac, digestive or neurologic manifestations. There is an urgent need for a vaccine because treatments are only effective at the initial phase of the infection, which is generally underdiagnosed. Selection and combination of antigens, adjuvants, and delivery platforms for vaccine formulations should be designed to trigger mixed humoral and cellular immune responses, considering that T. cruzi has a complex life cycle with both intracellular and bloodstream circulating parasite stages in the vertebrate host. Here we report the effectiveness of the vaccination with a T. cruzi-specific protein family (TcTASV), employing both recombinant proteins with aluminum hydroxide and recombinant baculovirus displaying a TcTASV antigen at the capsid. Vaccination stimulated immunological responses with production of lytic antibodies and antigen-specific CD4+ and CD8+ IFNɣ secreting lymphocytes. More than 90% of vaccinated animals survived after lethal challenges with T. cruzi while all control mice died before 30 days post infection. Vaccination also induced a strong decrease of chronic tissue parasitism, and generated immunological memory that allowed vaccinated and infected animals to control both the reactivation of the infection after immunosuppression as well as a second challenge with T. cruzi. Interestingly, inoculation with wild type baculovirus trained the immune system to partially protect mice against T. cruzi. In brief, we demonstrated, for the first time, that the combination of the baculovirus platform and the TcTASV family provides effective protection against Trypanosoma cruzi, being a promising vaccine for Chagas' disease.
Boletín de la Oficina Sanitaria Panamericana. Pan American Sanitary Bureau, 1987
PLOS ONE, Aug 11, 2014
<p>(<b>A</b>) Representative samples from a control donor and a <i>T. cru... more <p>(<b>A</b>) Representative samples from a control donor and a <i>T. cruzi</i>-infected individual. PBMC were stained with Abs to CD19, CD27, IgD, IgM and IgG, and analyzed by flow cytometry. Numbers correspond to the percentage of cells within the gate. (<b>B</b>) Box and whiskers (min to max) show the percentage of cells expressing the indicated markers for control (n = 8) and infected individuals (n = 18). Groups were compared by the Mann-Whitney nonparametric test or U-test and statistical significance (p values) is indicated.</p
Journal of Immunology, May 1, 2012
In previous studies we have shown that human chronic T. cruzi infection is associated with abnorm... more In previous studies we have shown that human chronic T. cruzi infection is associated with abnormalities of CD8+ and CD4+ T cell compartments, probably as a consequence of chronic antigenic stimulation by persisting parasites. In this study, we measured the levels of circulating B cell subsets in 25 patients chronically infected with T. cruzi and 19 non-infected controls (mean age±SD=41.0±12.2 and 34.9±10.6 y respectively). The results showed that T. cruzi-infected patients had higher percentages of CD19+CD27-IgD+ (naïve; mean%±SD=54.1±16.1) and lower percentages of CD19+CD27+ (Ag-experienced; mean%±SD=35.8±16.5) B lymphocytes compared to controls (mean%±SD=33.8±15.8 and 55.7±18.0, respectively, p<0.05), with similar levels of CD69 or CD86 activation markers. The observed memory B cell reduction comprised switched (IgD-) and no-switched (IgD+) subsets (mean%±SD=17.9±11.2 and 17.9±12.6, respectively) in relation to controls (mean%±SD=30.9±17.8 and 24.8±16.4, respectively; p<0.05). The proportion of CD19+CD27+CD138+ plasma cells in patients was lower than in the controls (mean%±SD=5.0±3.6 and 26.4±27.1 respectively; p<0.05), with no differences in CD19+CD10+ cell levels (immature; mean%±SD=5.6±4.7 and 4.3±3.3, respectively). The accumulation of naïve and loss of memory B cell and plasma cell subsets in chronic Chagas disease patients indicate that T. cruzi infection affects the phenotypic profile of the peripheral blood B cell-compartment. Support: FONCyT PICT 2007 N°1732
PLOS ONE, Aug 11, 2014
<p>The levels of sCD27 were measured by ELISA in individuals with different degrees of card... more <p>The levels of sCD27 were measured by ELISA in individuals with different degrees of cardiac dysfunction and controls. Bars represent the mean and SD for each group. Statistical significance was determined with One-way ANOVA followed by Bonferroni’s post-test. *p<0.05. <b><sup>ƒ</sup></b> N, normal and A, abnormal.</p
The Journal of Immunology
Trypanosoma cruzi was shown to induce the loss of parasite-specific IgG-producing B cells during ... more Trypanosoma cruzi was shown to induce the loss of parasite-specific IgG-producing B cells during the acute infection of mice, which was proposed to hamper B cell responses and favor parasite replication and chronicity (Zuñiga et al. 2002). Herein, we measured the levels of circulating memory and MZ-like B cells in 12 individuals chronically infected with T. cruzi and 9 healthy controls based on the expression of CD19, IgM IgD, IgG, and CD27. T. cruzi-infected individuals had significantly lower percentages of IgM+IgD-CD27+ (IgM-only), IgM-IgD-CD27+ (isotype-switched) and IgG+IgD-CD27+ memory B cells compared to controls (p<0.05). Also, the percentage of IgM+IgD+CD27+ (MZ-like) B cells was reduced in infected individuals while the proportion of IgG+IgD-CD27- memory B cells was increased (p<0.05). The levels of memory B cells were further analyzed according to ECG findings in infected individuals (asymptomatic [ASY] and chronic Chagas heart disease [CHD]). IgG+IgD-CD27+, IgM+IgD...
The Journal of Immunology
In previous studies we have shown that human chronic T. cruzi infection is associated with abnorm... more In previous studies we have shown that human chronic T. cruzi infection is associated with abnormalities of CD8+ and CD4+ T cell compartments, probably as a consequence of chronic antigenic stimulation by persisting parasites. In this study, we measured the levels of circulating B cell subsets in 25 patients chronically infected with T. cruzi and 19 non-infected controls (mean age±SD=41.0±12.2 and 34.9±10.6 y respectively). The results showed that T. cruzi-infected patients had higher percentages of CD19+CD27-IgD+ (naïve; mean%±SD=54.1±16.1) and lower percentages of CD19+CD27+ (Ag-experienced; mean%±SD=35.8±16.5) B lymphocytes compared to controls (mean%±SD=33.8±15.8 and 55.7±18.0, respectively, p<0.05), with similar levels of CD69 or CD86 activation markers. The observed memory B cell reduction comprised switched (IgD-) and no-switched (IgD+) subsets (mean%±SD=17.9±11.2 and 17.9±12.6, respectively) in relation to controls (mean%±SD=30.9±17.8 and 24.8±16.4, respectively; p<0....
Frontiers in Cellular and Infection Microbiology, 2017
Frontiers in Immunology, 2021
Experimental Parasitology, 2021
This is a PDF file of an article that has undergone enhancements after acceptance, such as the ad... more This is a PDF file of an article that has undergone enhancements after acceptance, such as the addition of a cover page and metadata, and formatting for readability, but it is not yet the definitive version of record. This version will undergo additional copyediting, typesetting and review before it is published in its final form, but we are providing this version to give early visibility of the article. Please note that, during the production process, errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.
Frontiers in Cellular and Infection Microbiology, 2020
Boletin De La Oficina Sanitaria Panamericana, 1987
Frontiers in cellular and infection microbiology, Feb 28, 2024
Research Square (Research Square), Apr 28, 2023
Chagas' is a neglected disease caused by the eukaryotic kinetoplastid parasite Trypanosoma cruzi.... more Chagas' is a neglected disease caused by the eukaryotic kinetoplastid parasite Trypanosoma cruzi. Currently there are about 8 million infected people worldwide, most of them at the chronic phase of the disease, which involves cardiac, digestive or neurologic manifestations. There is an urgent need for a vaccine because treatments are only effective at the initial phase of the infection, which is generally underdiagnosed. Selection and combination of antigens, adjuvants, and delivery platforms for vaccine formulations should be designed to trigger mixed humoral and cellular immune responses, considering that T. cruzi has a complex life cycle with both intracellular and bloodstream circulating parasite stages in the vertebrate host. Here we report the effectiveness of the vaccination with a T. cruzi-specific protein family (TcTASV), employing both recombinant proteins with aluminum hydroxide and recombinant baculovirus displaying a TcTASV antigen at the capsid. Vaccination stimulated immunological responses with production of lytic antibodies and antigen-specific CD4+ and CD8+ IFNɣ secreting lymphocytes. More than 90% of vaccinated animals survived after lethal challenges with T. cruzi while all control mice died before 30 days post infection. Vaccination also induced a strong decrease of chronic tissue parasitism, and generated immunological memory that allowed vaccinated and infected animals to control both the reactivation of the infection after immunosuppression as well as a second challenge with T. cruzi. Interestingly, inoculation with wild type baculovirus trained the immune system to partially protect mice against T. cruzi. In brief, we demonstrated, for the first time, that the combination of the baculovirus platform and the TcTASV family provides effective protection against Trypanosoma cruzi, being a promising vaccine for Chagas' disease.
Boletín de la Oficina Sanitaria Panamericana. Pan American Sanitary Bureau, 1987
PLOS ONE, Aug 11, 2014
<p>(<b>A</b>) Representative samples from a control donor and a <i>T. cru... more <p>(<b>A</b>) Representative samples from a control donor and a <i>T. cruzi</i>-infected individual. PBMC were stained with Abs to CD19, CD27, IgD, IgM and IgG, and analyzed by flow cytometry. Numbers correspond to the percentage of cells within the gate. (<b>B</b>) Box and whiskers (min to max) show the percentage of cells expressing the indicated markers for control (n = 8) and infected individuals (n = 18). Groups were compared by the Mann-Whitney nonparametric test or U-test and statistical significance (p values) is indicated.</p
Journal of Immunology, May 1, 2012
In previous studies we have shown that human chronic T. cruzi infection is associated with abnorm... more In previous studies we have shown that human chronic T. cruzi infection is associated with abnormalities of CD8+ and CD4+ T cell compartments, probably as a consequence of chronic antigenic stimulation by persisting parasites. In this study, we measured the levels of circulating B cell subsets in 25 patients chronically infected with T. cruzi and 19 non-infected controls (mean age±SD=41.0±12.2 and 34.9±10.6 y respectively). The results showed that T. cruzi-infected patients had higher percentages of CD19+CD27-IgD+ (naïve; mean%±SD=54.1±16.1) and lower percentages of CD19+CD27+ (Ag-experienced; mean%±SD=35.8±16.5) B lymphocytes compared to controls (mean%±SD=33.8±15.8 and 55.7±18.0, respectively, p<0.05), with similar levels of CD69 or CD86 activation markers. The observed memory B cell reduction comprised switched (IgD-) and no-switched (IgD+) subsets (mean%±SD=17.9±11.2 and 17.9±12.6, respectively) in relation to controls (mean%±SD=30.9±17.8 and 24.8±16.4, respectively; p<0.05). The proportion of CD19+CD27+CD138+ plasma cells in patients was lower than in the controls (mean%±SD=5.0±3.6 and 26.4±27.1 respectively; p<0.05), with no differences in CD19+CD10+ cell levels (immature; mean%±SD=5.6±4.7 and 4.3±3.3, respectively). The accumulation of naïve and loss of memory B cell and plasma cell subsets in chronic Chagas disease patients indicate that T. cruzi infection affects the phenotypic profile of the peripheral blood B cell-compartment. Support: FONCyT PICT 2007 N°1732
PLOS ONE, Aug 11, 2014
<p>The levels of sCD27 were measured by ELISA in individuals with different degrees of card... more <p>The levels of sCD27 were measured by ELISA in individuals with different degrees of cardiac dysfunction and controls. Bars represent the mean and SD for each group. Statistical significance was determined with One-way ANOVA followed by Bonferroni’s post-test. *p<0.05. <b><sup>ƒ</sup></b> N, normal and A, abnormal.</p
The Journal of Immunology
Trypanosoma cruzi was shown to induce the loss of parasite-specific IgG-producing B cells during ... more Trypanosoma cruzi was shown to induce the loss of parasite-specific IgG-producing B cells during the acute infection of mice, which was proposed to hamper B cell responses and favor parasite replication and chronicity (Zuñiga et al. 2002). Herein, we measured the levels of circulating memory and MZ-like B cells in 12 individuals chronically infected with T. cruzi and 9 healthy controls based on the expression of CD19, IgM IgD, IgG, and CD27. T. cruzi-infected individuals had significantly lower percentages of IgM+IgD-CD27+ (IgM-only), IgM-IgD-CD27+ (isotype-switched) and IgG+IgD-CD27+ memory B cells compared to controls (p<0.05). Also, the percentage of IgM+IgD+CD27+ (MZ-like) B cells was reduced in infected individuals while the proportion of IgG+IgD-CD27- memory B cells was increased (p<0.05). The levels of memory B cells were further analyzed according to ECG findings in infected individuals (asymptomatic [ASY] and chronic Chagas heart disease [CHD]). IgG+IgD-CD27+, IgM+IgD...
The Journal of Immunology
In previous studies we have shown that human chronic T. cruzi infection is associated with abnorm... more In previous studies we have shown that human chronic T. cruzi infection is associated with abnormalities of CD8+ and CD4+ T cell compartments, probably as a consequence of chronic antigenic stimulation by persisting parasites. In this study, we measured the levels of circulating B cell subsets in 25 patients chronically infected with T. cruzi and 19 non-infected controls (mean age±SD=41.0±12.2 and 34.9±10.6 y respectively). The results showed that T. cruzi-infected patients had higher percentages of CD19+CD27-IgD+ (naïve; mean%±SD=54.1±16.1) and lower percentages of CD19+CD27+ (Ag-experienced; mean%±SD=35.8±16.5) B lymphocytes compared to controls (mean%±SD=33.8±15.8 and 55.7±18.0, respectively, p<0.05), with similar levels of CD69 or CD86 activation markers. The observed memory B cell reduction comprised switched (IgD-) and no-switched (IgD+) subsets (mean%±SD=17.9±11.2 and 17.9±12.6, respectively) in relation to controls (mean%±SD=30.9±17.8 and 24.8±16.4, respectively; p<0....
Frontiers in Cellular and Infection Microbiology, 2017
Frontiers in Immunology, 2021
Experimental Parasitology, 2021
This is a PDF file of an article that has undergone enhancements after acceptance, such as the ad... more This is a PDF file of an article that has undergone enhancements after acceptance, such as the addition of a cover page and metadata, and formatting for readability, but it is not yet the definitive version of record. This version will undergo additional copyediting, typesetting and review before it is published in its final form, but we are providing this version to give early visibility of the article. Please note that, during the production process, errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.
Frontiers in Cellular and Infection Microbiology, 2020
Boletin De La Oficina Sanitaria Panamericana, 1987