scholarly journals α-Gal immunization positively impacts Trypanosoma cruzi colonization of heart tissue in a mouse model

2021 ◽  
Vol 15 (7) ◽  
pp. e0009613
Author(s):  
Gisele Macêdo Rodrigues da Cunha ◽  
Maíra Araújo Azevedo ◽  
Denise Silva Nogueira ◽  
Marianna de Carvalho Clímaco ◽  
Edward Valencia Ayala ◽  
...  
Keyword(s):  
Trypanosoma Cruzi ◽  
Parasitic Infection ◽  
Heart Tissue ◽  
Igg Antibody ◽  
Chronic Stage ◽  
Beneficial Effects ◽  
Virus Like Particle ◽  
Antibody Titers ◽  
High Parasite

Chagas disease, caused by the parasite Trypanosoma cruzi, is considered endemic in more than 20 countries but lacks both an approved vaccine and limited treatment for its chronic stage. Chronic infection is most harmful to human health because of long-term parasitic infection of the heart. Here we show that immunization with a virus-like particle vaccine displaying a high density of the immunogenic α-Gal trisaccharide (Qβ-αGal) induced several beneficial effects concerning acute and chronic T. cruzi infection in α1,3-galactosyltransferase knockout mice. Approximately 60% of these animals were protected from initial infection with high parasite loads. Vaccinated animals also produced high anti-αGal IgG antibody titers, improved IFN-γ and IL-12 cytokine production, and controlled parasitemia in the acute phase at 8 days post-infection (dpi) for the Y strain and 22 dpi for the Colombian strain. In the chronic stage of infection (36 and 190 dpi, respectively), all of the vaccinated group survived, showing significantly decreased heart inflammation and clearance of amastigote nests from the heart tissue.

scholarly journals Single-Shot Vaccines against Bovine Respiratory Syncytial Virus (BRSV): Comparative Evaluation of Long-Term Protection after Immunization in the Presence of BRSV-Specific Maternal Antibodies

Vaccines ◽  
2021 ◽  
Vol 9 (3) ◽  
pp. 236
Author(s):  
Jean François Valarcher ◽  
Sara Hägglund ◽  
Katarina Näslund ◽  
Luc Jouneau ◽  
Ester Malmström ◽  
...  
Keyword(s):  
Respiratory Syncytial Virus ◽  
Bovine Respiratory Syncytial Virus ◽  
Single Shot ◽  
Igg Antibody ◽  
Post Vaccination ◽  
Proteomic Data ◽  
Antibody Titers ◽  
Specific Igg ◽  
Syncytial Virus

The induction of long-lasting clinical and virological protection is needed for a successful vaccination program against the bovine respiratory syncytial virus (BRSV). In this study, calves with BRSV-specific maternally derived antibodies were vaccinated once, either with (i) a BRSV pre-fusion protein (PreF) and MontanideTM ISA61 VG (ISA61, n = 6), (ii) BRSV lacking the SH gene (ΔSHrBRSV, n = 6), (iii) a commercial vaccine (CV, n = 6), or were injected with ISA61 alone (n = 6). All calves were challenged with BRSV 92 days later and were euthanized 13 days post-infection. Based on clinical, pathological, and proteomic data, all vaccines appeared safe. Compared to the controls, PreF induced the most significant clinical and virological protection post-challenge, followed by ΔSHrBRSV and CV, whereas the protection of PreF-vaccinated calves was correlated with BRSV-specific serum immunoglobulin (Ig)G antibody responses 84 days post-vaccination, and the IgG antibody titers of ΔSHrBRSV- and CV-vaccinated calves did not differ from the controls on this day. Nevertheless, strong anamnestic BRSV- and PreF-specific IgG responses occurred in calves vaccinated with either of the vaccines, following a BRSV challenge. In conclusion, PreF and ΔSHrBRSV are two efficient one-shot candidate vaccines. By inducing a protection for at least three months, they could potentially improve the control of BRSV in calves.

Antipneumococcal Seroprotection Years After Vaccination in Allogeneic Hematopoietic Cell Transplant Recipients

2019 ◽  
Vol 71 (8) ◽  
pp. e301-e307
Author(s):  
Christine Robin ◽  
Mathilde Bahuaud ◽  
Rabah Redjoul ◽  
Mohamed Jeljeli ◽  
Mathieu Leclerc ◽  
...  
Keyword(s):  
Chronic Gvhd ◽  
Hematopoietic Cell ◽  
Cell Transplant ◽  
Hematopoietic Cell Transplant ◽  
Igg Antibody ◽  
Seroprotection Rate ◽  
Allogeneic Hematopoietic Cell Transplant ◽  
Cord Blood Unit ◽  
Antibody Titers

Abstract Background International guidelines recommend vaccinating allogeneic hematopoietic cell transplant (HCT) recipients at 3 months after transplant, giving 3 doses of pneumococcal conjugate vaccine (PCV) followed by either a dose of 23-valent pneumococcal polysaccharide vaccine (PSV23) or a fourth PCV dose in the case of graft-versus-host disease (GvHD). However, the long-term immunity after this regimen is unknown, and there is no recommendation from 24 months after transplant regarding boosts. Our objective was to assess the antipneumococcal antibody titers and seroprotection rates of allogeneic HCT recipients years after different schedules of vaccination. Methods We assessed 100 adult HCT recipients a median of 9.3 years (range: 1.7–40) after transplant. All patients had received at least one dose of PCV and were assessed for antipneumococcal immunoglobulin G (IgG) antibody titers against the 7 serotypes shared by PCV7, PCV13, and PSV23. Sixty-six percent of the patients had been vaccinated according to the current guidelines. Results Considering an IgG titer ≥ 0.35 µg/mL as protective for each serotype, the seroprotection rate was 50% for 7/7 serotypes and 70% for 5/7 serotypes, with no differences between the different vaccination schedules. The lack of seroprotection was associated with a transplant performed not in complete remission or from a cord-blood unit, a relapse after transplant, or chronic GvHD at assessment. Conclusion Because only half of the vaccinated patients had long-term protection, pending prospective studies defining the best boost program after the initial one, we recommend the assessment of specific IgG titers starting from 24 months to decide for further doses.

scholarly journals Joint Investigation of Two-Month Post-Diagnosis IgG Antibody Levels and Psychological Measures for Assessing Longer Term Multi-Faceted Recovery among COVID-19 Cases in Northern Cyprus

2020 ◽  
Author(s):  
Burc Barin ◽  
Banu Elcin Yoldascan ◽  
Fatma Savaskan ◽  
Goncagul Ozbalikci ◽  
Tugce Karaderi ◽  
...  
Keyword(s):  
Community Intervention ◽  
Recovery Period ◽  
Traumatic Experience ◽  
Multidisciplinary Research ◽  
Igg Antibody ◽  
Northern Cyprus ◽  
Antibody Titers ◽  
Psychological Experiences ◽  
The Impact

Following the outbreak of COVID-19, multidisciplinary research focusing on the long-term effects of the COVID-19 infection and the complete longer term recovery is still scarce. With regards to long-term consequences, biomarkers of physiological effects as well as the psychological experiences are of significant importance for comprehensively understanding the whole COVID-19 recovery period. The present research surveys the IgG antibody titers and the impact of COVID-19 as a traumatic experience in the aftermath of the active infection period, around two months after diagnosis, in a subset of COVID-19 patients from the first wave of the outbreak in Northern Cyprus. Associations of antibody titers and psychological survey measures with baseline characteristics and disease severity were explored, and correlations among various measures were evaluated. Of the 47 serology tests conducted for presence of IgG antibodies, 39 (83%) were positive. We identified trends demonstrating individuals experiencing severe or critical COVID-19 disease and/or those with comorbidities are more heavily impacted both physiologically and mentally, with higher IgG titers and negative psychological experience compared to those with milder disease and without comorbidities. We also observed that more than half of the COVID-19 cases had negative psychological experiences, being subjected to discrimination and/or verbal harassment/insult, by family/friends. In summary, as the first study co-evaluating immune response together with mental status, our findings suggest that further multidisciplinary research in larger sample populations as well as community intervention plans are needed to holistically address the physiological and psychological effects of COVID-19 among the cases in the long-term.

scholarly journals Humoral response to the BBIBP-CorV vaccine over time in healthcare workers with or without exposure to SARS-CoV-2

2021 ◽  
Author(s):  
María Noel Badano ◽  
Florencia Sabbione ◽  
Irene Keitelman ◽  
Matias Pereson ◽  
Natalia Aloisi ◽  
...  
Keyword(s):  
Single Dose ◽  
Sharp Increase ◽  
Healthcare Workers ◽  
Humoral Response ◽  
Igg Antibody ◽  
Antibody Titers ◽  
Humoral Responses ◽  
Antibody Levels ◽  
Over Time

AbstractSARS-CoV-2-specific humoral response was analyzed over time in a group of healthcare workers with or without exposure to SARS-CoV-2, who underwent vaccination with BBIBP-CorV (Sinopharm) vaccine in Argentina.Seroconversion rates in unexposed subjects after the first and second doses were 40% and 100%, respectively, showing a significant increase in antibody concentrations from dose 1 to dose 2 (p<0.0001).The highest antibody concentrations were found in younger subjects and women, remaining significantly associated in a multivariable linear regression model (p=0.005).A single dose of the BBIBP-CorV vaccine induced a strong antibody response in individuals with prior SARS-CoV-2infection, while a second dose did not increase this response. A sharp increase in antibody concentrations was observed following SARS-CoV-2 infection in those participants who became infected after the first and second doses (p=0.008).Individuals with SARS-CoV-2 exposure prior to vaccination showed significantly higher anti-spike IgG antibody levels, at all-time points, than those not exposed (p<0.001). Higher antibody titers were induced by a single dose in previously SARS-CoV-2 infected individuals than those induced in naïve subjects by two doses of the vaccine (p<0.0001). Three months after the second dose both groups showed a decline in antibody levels, being more abrupt in unexposed subjects.Overall, our results showed a trend towards lower antibody concentrations over time following BBIBP-CorV vaccination. Sex and age seem to influence the magnitude of the humoral response in unexposed subjects while the combination of exposure to SARS-CoV-2 plus vaccination, whatever the sequence of the events was, produced a sharp increase in antibody levels.Evaluation of the humoral responses over time and the analysis of the induction and persistence of memory B and T cell responses, are needed to assess long-term immune protection induced by BBIBP-CorV vaccine.

scholarly journals Joint Investigation of 2-Month Post-diagnosis IgG Antibody Levels and Psychological Measures for Assessing Longer Term Multi-Faceted Recovery Among COVID-19 Cases in Northern Cyprus

2021 ◽  
Vol 8 ◽  
Author(s):  
Burc Barin ◽  
Banu Elcin Yoldascan ◽  
Fatma Savaskan ◽  
Goncagul Ozbalikci ◽  
Tugce Karaderi ◽  
...  
Keyword(s):  
Community Intervention ◽  
Traumatic Experience ◽  
Long Term Effects ◽  
Multidisciplinary Research ◽  
Igg Antibody ◽  
Northern Cyprus ◽  
Antibody Titers ◽  
Psychological Experiences ◽  
The Impact

Following the outbreak of COVID-19, multidisciplinary research focusing on the long-term effects of the COVID-19 infection and the complete recovery is still scarce. With regards to long-term consequences, biomarkers of physiological effects as well as the psychological experiences are of significant importance for comprehensively understanding the complete COVID-19 recovery. The present research surveys the IgG antibody titers and the impact of COVID-19 as a traumatic experience in the aftermath of the active infection period, around 2 months after diagnosis, in a subset of COVID-19 patients from the first wave (March-April 2020) of the outbreak in Northern Cyprus. Associations of antibody titers and psychological survey measures with baseline characteristics and disease severity were explored, and correlations among various measures were evaluated. Of the 47 serology tests conducted for presence of IgG antibodies, 39 (83%) were positive. We identified trends demonstrating individuals experiencing severe or critical COVID-19 disease and/or those with comorbidities are more heavily impacted both physiologically and mentally, with higher IgG titers and negative psychological experience compared to those with milder disease and without comorbidities. We also observed that more than half of the COVID-19 cases had negative psychological experiences, being subjected to discrimination and verbal harassment/insult, by family/friends. In summary, as the first study co-evaluating immune response together with mental status in COVID-19, our findings suggest that further multidisciplinary research in larger sample populations as well as community intervention plans are needed to holistically address the physiological and psychological effects of COVID-19 among the cases.

scholarly journals TNF/TNFR1 signaling up-regulates CCR5 expression by CD8+ T lymphocytes and promotes heart tissue damage during Trypanosoma cruzi infection: beneficial effects of TNF-α blockade

2008 ◽  
Vol 103 (4) ◽  
pp. 375-385 ◽  
Author(s):  
Karina Kroll-Palhares ◽  
Jaline Coutinho Silvério ◽  
Andrea Alice da Silva ◽  
Vladimir Michailowsky ◽  
Ana Paula Marino ◽  
...  
Keyword(s):  
T Lymphocytes ◽  
Trypanosoma Cruzi ◽  
Tissue Damage ◽  
Heart Tissue ◽  
Ccr5 Expression ◽  
Beneficial Effects ◽  
Cd8 T Lymphocytes ◽  
Tnf Α ◽  
Cruzi Infection

scholarly journals Spatial metabolomics identifies localized chemical changes in heart tissue during chronic cardiac Chagas disease

2020 ◽  
Author(s):  
Danya A. Dean ◽  
Gautham ◽  
Jair L. Siqueira-Neto ◽  
James H. McKerrow ◽  
Pieter C. Dorrestein ◽  
...  
Keyword(s):  
Trypanosoma Cruzi ◽  
Chagas Disease ◽  
Parasite Burden ◽  
Heart Tissue ◽  
Blood Transfusions ◽  
Organ Transplants ◽  
Chronic Stage ◽  
Congenital Transmission ◽  
Cardiac Symptoms ◽  
The Impact

AbstractChagas disease (CD) is one of thirteen neglected tropical diseases caused by the parasite Trypanosoma cruzi. CD is a vector-borne disease transmitted by triatomines but CD can also be transmitted through blood transfusions, organ transplants and congenital transmission. While endemic to Latin America, T. cruzi infects 7-8 million people worldwide and can induce severe cardiac symptoms including apical aneurysms, thromboembolisms and arrhythmias during the chronic stage of CD. However, these cardiac clinical manifestations and CD disease pathogenesis are not fully understood. Using spatial metabolomics (chemical cartography), we sought to understand the localized impact of infection on the cardiac metabolome of mice chronically infected with two divergent T. cruzi strains. Our data showed chemical differences in localized cardiac regions upon chronic T. cruzi infection, indicating that parasite infection changes the host metabolome at select sites in chronic CD. These sites were distinct from the sites of highest parasite burden. In addition, we identified acylcarnitines and phosphocholines as discriminatory chemical families within each heart region, comparing infected and uninfected samples. Overall, our study indicated overall and positional metabolic differences common to infection with different T. cruzi strains, and identified select infection-modulated pathways. These results provide further insight into CD pathogenesis and demonstrate the advantage of a spatial perspective to understand infectious disease tropism.Author SummaryChagas disease (CD) is a tropical disease caused by the parasite Trypanosoma cruzi. CD originated in South America; however, there are now 7-8 million people infected worldwide due to population movements. CD is transmitted through a triatomine vector, organ transplants, blood transfusions and congenital transmission. It occurs in two stages, an acute stage (usually asymptomatic) and the chronic stage. Chronic stage CD presents with severe cardiac symptoms such as heart failure, localized aneurysms and cardiomyopathy. Unfortunately, what causes severe cardiac symptoms in some individuals in chronic CD is not fully understood. Therefore, we used liquid chromatography-tandem mass spectrometry to analyze the heart tissue of chronically T. cruzi-infected and uninfected mice, to understand the impact of infection on the tissue metabolome. We identified discriminatory small molecules related to T. cruzi infection. We also determined that regions with the highest parasite burden are distinct from the regions with the largest changes in overall metabolite profile; these locations of high metabolic perturbation provide a molecular mechanism to why localized cardiac symptoms occur in CD. Overall, our work gives insight to chronic cardiac CD symptom development and shapes a framework for novel treatment and biomarker development.

scholarly journals Anti-CD4 abrogates rejection and reestablishes long-term tolerance to syngeneic newborn hearts grafted in mice chronically infected with Trypanosoma cruzi.

1992 ◽  
Vol 175 (1) ◽  
pp. 29-39 ◽  
Author(s):  
R R dos Santos ◽  
M A Rossi ◽  
J L Laus ◽  
J S Silva ◽  
W Savino ◽  
...  
Keyword(s):  
T Cells ◽  
Trypanosoma Cruzi ◽  
Cd4 T Cells ◽  
Heart Tissue ◽  
Major Mechanism ◽  
Heart Graft ◽  
Heart Pathology

The contribution of autoimmunity in the genesis of chronic Chagas' heart pathology is not clear. In the present study, we show that: (a) BALB/c mice chronically infected with Trypanosoma cruzi reject syngeneic newborn hearts; (b) in vivo treatment with anti-CD4 but not anti-CD8 monoclonal antibodies (mAbs) abrogates rejection; (c) CD4+ T cells from chronically infected mice proliferate in vitro to syngeneic myocardium antigens and induce heart graft destruction when injected in situ; (d) anti-CD4 treatment of chronically infected mice establishes long-term tolerance to syngeneic heart grafts; and (e) the state of tolerance is related to in vitro and in vivo unresponsiveness of the CD4+ T cells. These findings allow us to suggest that autoimmunity is the major mechanism implicated in the rejection of syngeneic heart tissues grafted into the pinna of the ear of mice chronically infected with T. cruzi. The similarity of the lesions to those found in humans suggests that autoimmunity is involved in the pathogenesis of chagasic cardiomyopathy in humans. Moreover, this could imply therapeutic strategies by reestablishing long-term tissue-specific tolerance with anti-CD4 mAb treatment, mediating anergy, or deleting the responder CD4+ T cells to heart tissue antigens.

scholarly journals Trypanosoma cruzi amastigotes that persist in the colon during chronic stage murine infections have a reduced replication rate

Open Biology ◽  
2020 ◽  
Vol 10 (12) ◽  
pp. 200261
Author(s):  
Alexander I. Ward ◽  
Francisco Olmo ◽  
Richard L. Atherton ◽  
Martin C. Taylor ◽  
John M. Kelly
Keyword(s):  
Trypanosoma Cruzi ◽  
Acute Stage ◽  
Host Cells ◽  
Replication Rate ◽  
Chronic Infections ◽  
Chronic Stage ◽  
Highly Sensitive ◽  
Parasite Replication ◽  
Reduced Rate

Chronic Trypanosoma cruzi infections are typically lifelong, with small numbers of parasites surviving in restricted tissue sites, which include the gastrointestinal tract. There is considerable debate about the replicative status of these persistent parasites and whether there is a role for dormancy in long-term infection. Here, we investigated T. cruzi proliferation in the colon of chronically infected mice using 5-ethynyl-2′deoxyuridine incorporation into DNA to provide ‘snapshots’ of parasite replication status. Highly sensitive imaging of the extremely rare infection foci, at single-cell resolution, revealed that parasites are three times more likely to be in S-phase during the acute stage than during the chronic stage. By implication, chronic infections of the colon are associated with a reduced rate of parasite replication. Despite this, very few host cells survived infection for more than 14 days, suggesting that T. cruzi persistence continues to involve regular cycles of replication, host cell lysis and re-infection. We could find no evidence for wide-spread dormancy in parasites that persist in this tissue reservoir.

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