scholarly journals Strong anti-viral responses in pediatric COVID-19 patients in South Brazil

2021 ◽  
Author(s):  
Tiago Fazolo ◽  
Karina Lima ◽  
Julia C. Fontoura ◽  
Priscila Oliveira de Souza ◽  
Gabriel Hilario ◽  
...  
Keyword(s):  
T Cell ◽  
Immune Responses ◽  
T Cell Responses ◽  
Humoral Immune ◽  
Cell Responses ◽  
Humoral Immune Responses ◽  
Hla Dr ◽  
Data Points ◽  
Viral Responses ◽  
Immune Profiling

AbstractEpidemiological evidence that COVID-19 manifests as a milder disease in children compared to adults has been reported by numerous studies, but the mechanisms underlying this phenomenon have not been characterized. It is still unclear how frequently children get infected, and/or generate immune responses to SARS-CoV-2. We have performed immune profiling of pediatric and adult COVID-19 patients in Brazil, producing over 38 thousand data points, asking if cellular or humoral immune responses could help explain milder disease in children. In this study, pediatric COVID-19 patients presented high viral titers. Though their non-specific immune profile was dominated by naive, non-activated lymphocytes, their dendritic cells expressed high levels of HLA-DR and were low in CX3CR1, indicating competence to generate immune responses that are not targeted to inflamed tissue. Finally, children formed strong specific antibody and T cell responses for viral structural proteins. Children’s T cell responses differed from adults in that their CD8+ TNFα+ T cell responses were low for S peptide but significantly higher against N and M peptide pools. Altogether, our data support a scenario in which SARS-CoV-2 infected children may contribute to transmission, though generating strong and differential responses to the virus that might associate with protection in pediatric COVID-19 presentation.

scholarly journals Strong specific anti-viral responses in pediatric COVID-19 patients in South Brazil

2021 ◽  
Author(s):  
Tiago Fazolo ◽  
Karina Lima ◽  
Julia Fontoura ◽  
Priscila de Souza ◽  
Gabriel Hilario ◽  
...  
Keyword(s):  
T Cell ◽  
Immune Responses ◽  
T Cell Responses ◽  
Humoral Immune ◽  
Cell Responses ◽  
Humoral Immune Responses ◽  
Hla Dr ◽  
Data Points ◽  
Viral Responses ◽  
Immune Profiling

Abstract Epidemiological evidence that COVID-19 manifests as a milder disease in children compared to adults has been reported by numerous studies, but the mechanisms underlying this phenomenon have not been characterized. It is still unclear how frequently children get infected, and/or generate immune responses to SARS-CoV-2. We have performed immune profiling of pediatric and adult COVID-19 patients in Brazil, producing over 38 thousand data points, asking if cellular or humoral immune responses could help explain milder disease in children. In this study, pediatric COVID-19 patients presented high viral titers. Though their non-specific immune profile was dominated by naive, non-activated lymphocytes, their dendritic cells expressed high levels of HLA-DR and were low in CX3CR1, indicating competence to generate immune responses that are not targeted to inflamed tissue. Finally, children formed strong specific antibody and T cell responses for viral structural proteins. Children’s T cell responses differed from adults in that their CD8+ TNFα+ T cell responses were low for S peptide but significantly higher against N and M peptide pools. Altogether, our data support a scenario in which SARS-CoV-2 infected children may contribute to transmission, though generating strong and differential responses to the virus that might associate with protection in pediatric COVID-19 presentation.

EBV-specific immune responses in patients with multiple sclerosis responding to IFNβ therapy

2011 ◽  
Vol 18 (5) ◽  
pp. 605-609 ◽  
Author(s):  
Manuel Comabella ◽  
Kristina Kakalacheva ◽  
Jordi Río ◽  
Christian Münz ◽  
Xavier Montalban ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
T Cell ◽  
Immune Responses ◽  
T Cell Responses ◽  
Lytic Replication ◽  
Nuclear Antigen ◽  
Humoral Immune ◽  
Cell Responses ◽  
Humoral Immune Responses ◽  
Specific Igg

Background: Symptomatic primary infection with the human γ-herpesvirus Epstein–Barr virus (EBV) and elevated immune responses to EBV are associated with the development and progression of multiple sclerosis (MS). Interferon-beta (IFNβ), first-line treatment for relapse-onset MS, exhibits complex immunoregulatory and antiviral activities. Objective: To determine EBV-specific immune responses in patients with MS during IFNβ therapy. Methods: We evaluated cellular and humoral immune responses to EBV- and human cytomegalovirus (HCMV)-encoded antigens in patients with MS before and 1 year after IFNβ treatment by ELISA and flow cytometry. Twenty-eight patients with MS who showed a clinical response to IFNβ as defined by the absence of relapses and lack of progression on the Expanded Disability Status Scale score during the first 2 years of treatment were included. Results: Clinically effective IFNβ-therapy was associated with a downregulation of proliferative T cell responses to the latent EBV nuclear antigen-1 (EBNA1). EBNA1-specific IgG responses as well as cellular and humoral immune responses to MHC class I restricted EBV antigens expressed during lytic replication and viral B cell transformation were similar before and after IFNβ therapy. Although HCMV-specific IgG levels slightly decreased, proliferative T-cell responses towards HCMV antigens remained unchanged during IFNβ therapy. Conclusion: Clinically effective IFNβ therapy is associated with a reduction of proliferative T-cell responses to EBNA1.

scholarly journals 479 A lymph-node targeted amphiphile vaccine induces potent cellular and humoral immunity to SARS-CoV-2

2020 ◽  
Vol 8 (Suppl 3) ◽  
pp. A513-A513
Author(s):  
Martin Steinbuck ◽  
Peter DeMuth ◽  
Lochana Seenappa ◽  
Christopher Haqq ◽  
Aniela Jakubowski ◽  
...  
Keyword(s):  
Immune Response ◽  
T Cells ◽  
T Cell ◽  
Immune Responses ◽  
Receptor Binding ◽  
Intracellular Cytokine Staining ◽  
T Cell Responses ◽  
Humoral Immune ◽  
Cell Responses ◽  
Humoral Immune Responses

BackgroundThe SARS-CoV-2 pandemic’s public health, economic, and social impacts mandate urgent development of effective vaccines to contain or eradicate infection. To that end, we evaluated a novel amphiphile (AMP) vaccine adjuvant, AMP-CpG, composed of diacyl lipid-modified CpG, admixed with the SARS-CoV-2 Spike-2 receptor binding domain (Spike RBD) protein for immunization (ELI 005) in two mouse models. AMP immunogens are efficiently delivered to lymph nodes, where innate and adaptive immune responses are generated.MethodsFemale, 6 to 8-week-old C57BL/6J and BALB/c mice and 37-week-old C57BL/6J mice received two or more doses of benchmark (alum or CpG) or AMP-modified vaccines, comprised of Spike RBD protein and AMP-CpG adjuvant, subcutaneously injected into the tail base in two-week intervals. Antigen was dose spared to determine if AMP-CpG would maintain the immune response. Cellular immune responses were determined via ELISpot analysis of IFNγ production by splenocytes, intracellular cytokine staining of peripheral blood and lung-resident T-cells, and flowcytometric bead array analysis of Th1/2/17 cytokines. Humoral immune responses were determined via blood serum ELISAs to determine sera antibody binding titers, and pseudoviral neutralization assays for comparison to human convalescent serum.ResultsCompared to alum, AMP immunization induced 29-fold higher antigen-specific T cells which produced multiple Th1 cytokines and trafficked into lung parenchyma. Antibody responses favored Th1 isotypes (IgG2bc, IgG3) and potently neutralized Spike-2-ACE2 receptor binding, with titers >100-fold higher than the natural immune response from convalescent COVID-19 patients; responses were maintained despite 10-fold dose-reduction in Spike antigen. Both cellular and humoral immune responses were preserved in aged mice.ConclusionsELI-005 exhibits the qualities of an optimal SARS-CoV-2 vaccine, which should (1) induce robust and durable CD8+ and CD4+ T cell responses, (2) elicit high magnitude neutralizing antibodies, (3) produce Th1 bias in the elicited antibody and T cell responses, (4) potentially expand pre-existing cross-reactive T cells, (5) enable dose-sparing of required immunogens to improve the speed and cost of broad vaccination campaigns, and (6) be efficacious in elderly populations. These advantages merit clinical translation to SARS-CoV-2 and other protein subunit vaccines.

scholarly journals Melioidosis Patient Survival Correlates With Strong IFN-γ Secreting T Cell Responses Against Hcp1 and TssM

2021 ◽  
Vol 12 ◽  
Author(s):  
Sineenart Sengyee ◽  
Atchara Yarasai ◽  
Rachan Janon ◽  
Chumpol Morakot ◽  
Orawan Ottiwet ◽  
...  
Keyword(s):  
T Cell ◽  
Immune Responses ◽  
Clinical Manifestations ◽  
T Cell Responses ◽  
Peptide Pool ◽  
Humoral Immune ◽  
Cell Responses ◽  
Humoral Immune Responses ◽  
Healthy Donors ◽  
Ifn Γ

Melioidosis, caused by the Gram-negative bacterium Burkholderia pseudomallei, is a serious infectious disease with diverse clinical manifestations. The morbidity and mortality of melioidosis is high in Southeast Asia and no licensed vaccines currently exist. This study was aimed at evaluating human cellular and humoral immune responses in Thai adults against four melioidosis vaccine candidate antigens. Blood samples from 91 melioidosis patients and 100 healthy donors from northeast Thailand were examined for immune responses against B. pseudomallei Hcp1, AhpC, TssM and LolC using a variety of cellular and humoral immune assays including IFN-γ ELISpot assays, flow cytometry and ELISA. PHA and a CPI peptide pool were also used as control stimuli in the ELISpot assays. Hcp1 and TssM stimulated strong IFN-γ secreting T cell responses in acute melioidosis patients which correlated with survival. High IFN-γ secreting CD4+ T cell responses were observed during acute melioidosis. Interestingly, while T cell responses of melioidosis patients against the CPI peptide pool were low at the time of enrollment, the levels increased to the same as in healthy donors by day 28. Although high IgG levels against Hcp1 and AhpC were detected in acute melioidosis patients, no significant differences between survivors and non-survivors were observed. Collectively, these studies help to further our understanding of immunity against disease following natural exposure of humans to B. pseudomallei as well as provide important insights for the selection of candidate antigens for use in the development of safe and effective melioidosis subunit vaccines.

scholarly journals Pediatric COVID-19 patients in South Brazil show abundant viral mRNA and strong specific anti-viral responses

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Tiago Fazolo ◽  
Karina Lima ◽  
Julia C. Fontoura ◽  
Priscila Oliveira de Souza ◽  
Gabriel Hilario ◽  
...  
Keyword(s):  
T Cell ◽  
T Cell Responses ◽  
Peptide Pool ◽  
Viral Mrna ◽  
Humoral Immune ◽  
Cell Responses ◽  
Humoral Immune Responses ◽  
The Difference ◽  
Viral Responses ◽  
Underlying Mechanisms

AbstractCOVID-19 manifests as a milder disease in children than adults, but the underlying mechanisms are not fully characterized. Here we assess the difference in cellular or humoral immune responses of pediatric and adult COVID-19 patients to see if these factors contribute to the severity dichotomy. Children’s non-specific immune profile is dominated by naive lymphocytes and HLA-DRhighCX3CR1low dendritic cells; meanwhile, children show strong specific antibody and T cell responses for viral structural proteins, with their T cell responses differing from adults by having weaker CD8+TNF+ T cells responses to S peptide pool but stronger responses to N and M peptide pools. Finally, viral mRNA is more abundant in pediatric patients. Our data thus support a scenario in which SARS-CoV-2 infected children contribute to transmission yet are less susceptible to COVID-19 symptoms due to strong and differential responses to the virus.

Effect of epitopes derived from the mutated region of cytoplasmatic nucleophosmine 1 (NPM1) on CD4+ and CD8+ T-cell responses in patients with acute myeloid leukemia.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. 6567-6567
Author(s):  
Jochen Greiner ◽  
Yoko Ono ◽  
Susanne Hofmann ◽  
Vanessa Schneider ◽  
Anita Schmitt ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Immune Responses ◽  
Healthy Volunteers ◽  
Cd4 T Cells ◽  
T Cell Responses ◽  
Cd8 T Cell ◽  
Chromium Release ◽  
Cell Responses ◽  
Hla Dr

6567 Background: Mutations of the nucleophosmin gene (NPM1mut) are one of the most frequent molecular alterations in AML and constitute an important prognostic marker. The impact of NPM1mut on leukemogenesis and progression remains to be elucidated. Immune responses against NPM1mut might contribute to the favourable prognosis of AML patients with NPM1mut. Therefore, we examined T cell responses against NPM1mut. Methods: NPM1 wildtype as well as NPM1mut were screened for HLA-A*0201 binding T cell epitopes with the help of different algorithm programs. Ten peptides with most favourable characteristics were tested with ELISpot analysis for interferon-γ and granzyme B in 33 healthy volunteers and 30 AML patients. Tetramer assays against most interesting epitopes were performed and chromium release assays were used to show the cytotoxicity of peptide-specific CD8+ T cells. Moreover, HLA-DR-binding epitopes were used to test the role of CD4+ T cells in NPM1 immunogenicity. Results: Two epitopes (#1 and #3) derived from NPM1mut induced CD8+ T cell responses in a high frequency. In healthy volunteers, immune responses were detected in 39%/18% against #1 and #3, and in 33%/44% of NPM1mut AML patients against #1 and #3. NPM1-peptide primed effector T cells showed specific lysis of pulsed T2 cells as well as leukemic blasts in chromium release assays. In tetramer assays a significant CD8+ T cell population could be detected. To obtain a robust and continuous T cell reaction, the help of CD4+ T cells is indispensable. Therefore, we investigated the increase of CD8+ T cell responses by the activation of CD4+ T cells stimulated with longer peptides called overlapping peptides (OL). Potent HLA-DR epitopes were predicted and several favourable peptides (OL 1 to 8) were synthesized. OL8 showed favourable results to activate both CD8+ and CD4+ T cells. Conclusions: Taken together, NPM1mut represents a candidate for immunotherapeutic approaches and we hypothesize that it is also potentially involved in immunogenic rejection of NPM1mut leukemic blasts. Therefore, NPM1mut is a promising target structure for specific immunotherapies in AML patients.

scholarly journals SARS-CoV-2 specific T cell and humoral immune responses upon vaccination with BNT162b2

2021 ◽  
Author(s):  
Junko S Takeuchi ◽  
Ami Fukunaga ◽  
Shohei Yamamoto ◽  
Akihito Tanaka ◽  
Kouki Matsuda ◽  
...  
Keyword(s):  
T Cell ◽  
Immune Responses ◽  
Neutralizing Antibodies ◽  
T Cell Responses ◽  
Neutralizing Antibody ◽  
Igg Antibody ◽  
Humoral Immune ◽  
Cell Responses ◽  
Cell Assays ◽  
Specific Igg

Background. The humoral and cellular immune responses against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) upon coronavirus disease 2019 (COVID-19) vaccination remain to be clarified. Hence, we aimed to investigate the chronological changes in SARS-CoV-2 specific IgG antibody, neutralizing antibody, and T cell responses during and after receiving the BNT162b2 vaccine. Methods. We performed serological, neutralization, and T cell assays among 100 hospital workers aged 22-73 years who received the vaccine. We conducted five surveys on day 1, day 15, day 29 (seven days after the second dose), day 61, and days 82-96 following the first dose. Results. SARS-CoV-2 spike protein-specific IgG (IgG-S) titers and T cell responses increased significantly following the first vaccination dose. The highest titers were observed on day 29 and decreased gradually until the end of the follow-up period. There was no correlation between IgG-S and T cell responses. Notably, T cell responses were detected on day 15, earlier than the onset of neutralizing activity. Conclusions. This study demonstrated that both IgG-S and T cell responses were detected before acquiring sufficient levels of SARS-CoV-2 neutralizing antibodies. These early immune responses are sustained for approximately six-ten weeks following the second vaccination dose.

scholarly journals SARS-CoV-2 ferritin nanoparticle vaccine induces robust innate immune activity driving polyfunctional spike-specific T cell responses

npj Vaccines ◽  
2021 ◽  
Vol 6 (1) ◽  
Author(s):  
Joshua M. Carmen ◽  
Shikha Shrivastava ◽  
Zhongyan Lu ◽  
Alexander Anderson ◽  
Elaine B. Morrison ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
T Cell Responses ◽  
Innate Immune ◽  
Humoral Immune ◽  
Cell Responses ◽  
Adaptive Immune ◽  
Humoral Immune Responses ◽  
Specific Memory ◽  
Antigen Presenting

AbstractThe emergence of variants of concern, some with reduced susceptibility to COVID-19 vaccines underscores consideration for the understanding of vaccine design that optimizes induction of effective cellular and humoral immune responses. We assessed a SARS-CoV-2 spike-ferritin nanoparticle (SpFN) immunogen paired with two distinct adjuvants, Alhydrogel® or Army Liposome Formulation containing QS-21 (ALFQ) for unique vaccine evoked immune signatures. Recruitment of highly activated multifaceted antigen-presenting cells to the lymph nodes of SpFN+ALFQ vaccinated mice was associated with an increased frequency of polyfunctional spike-specific memory CD4+ T cells and Kb spike-(539–546)-specific long-lived memory CD8+ T cells with effective cytolytic function and distribution to the lungs. The presence of this epitope in SARS-CoV, suggests that generation of cross-reactive T cells may be induced against other coronavirus strains. Our study reveals that a nanoparticle vaccine, combined with a potent adjuvant that effectively engages innate immune cells, enhances SARS-CoV-2-specific durable adaptive immune T cell responses.

scholarly journals Characterization of SARS-CoV-2-Specific Humoral and Cellular Immune Responses Induced by Inactivated COVID-19 Vaccines in a Real-World Setting

2021 ◽  
Vol 12 ◽  
Author(s):  
Ziwei Li ◽  
Tiandan Xiang ◽  
Boyun Liang ◽  
Hui Deng ◽  
Hua Wang ◽  
...  
Keyword(s):  
T Cell ◽  
Immune Responses ◽  
Real World ◽  
Vaccine Dose ◽  
T Cell Responses ◽  
Neutralizing Antibody ◽  
Humoral Immune ◽  
Cell Responses ◽  
Effector Cytokines

While the immunogenicity of inactivated vaccines against coronavirus disease 2019 (COVID‐19) has been characterized in several well-conducted clinical trials, real-world evidence concerning immune responses against severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) raised by such vaccines is currently missing. Here, we comprehensively characterized various parameters of SARS-CoV-2-specific cellular and humoral immune responses induced by inactivated COVID-19 vaccines in 126 individuals under real-world conditions. After two doses of vaccination, S-receptor binding domain IgG (S-RBD IgG) and neutralizing antibody (NAb) were detected in 87.06% (74/85) and 78.82% (67/85) of individuals, respectively. Female participants developed higher concentrations of S-RBD IgG and NAb compared to male vaccinees. Interestingly, a longer dosing interval between the first and second vaccination resulted in a better long-term SARS-CoV-2 S-RBD IgG response. The frequencies of CD4+ T cells that produce effector cytokines (IFN-γ, IL-2, and TNF-α) in response to stimulation with peptide pools corresponding to the SARS-CoV-2 spike (S), nucleocapsid (N) or membrane (M) protein were significantly higher in individuals received two doses of vaccine than those received one dose of vaccine and unvaccinated individuals. S, N, or M-specific CD4+ and CD8+ T cell responses were detectable in 95.83% (69/72) and 54.16% (39/72) of double-vaccinated individuals, respectively. The longitudinal analysis demonstrated that CD4+ T cell responses recognizing S, N, and M waned quickly after a single vaccine dose, but were boosted and became more sustained following a second dose. Overall, we provide a comprehensive characterization of immune responses induced by inactivated COVID-19 vaccines in real-world settings, suggesting that both humoral and cellular SARS-CoV-2-specific immunity are elicited in the majority of individuals after two doses of inactivated COVID-19 vaccines.

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