scholarly journals IL-12 DNA as molecular vaccine adjuvant increases the cytotoxic T cell responses and breadth of humoral immune responses in SIV DNA vaccinated macaques

2012 ◽  
Vol 8 (11) ◽  
pp. 1620-1629 ◽  
Author(s):  
Rashmi Jalah ◽  
Vainav Patel ◽  
Viraj Kulkarni ◽  
Margherita Rosati ◽  
Candido Alicea ◽  
...  
Keyword(s):  
T Cell ◽  
Immune Responses ◽  
T Cell Responses ◽  
Cytotoxic T Cell ◽  
Vaccine Adjuvant ◽  
Humoral Immune ◽  
Cell Responses ◽  
Humoral Immune Responses ◽  
Cytotoxic T Cell Responses

scholarly journals Killer artificial antigen-presenting cells: a novel strategy to delete specific T cells

Blood ◽  
2008 ◽  
Vol 111 (7) ◽  
pp. 3546-3552 ◽  
Author(s):  
Christian Schütz ◽  
Martin Fleck ◽  
Andreas Mackensen ◽  
Alessia Zoso ◽  
Dagmar Halbritter ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Immune Responses ◽  
Fas Ligand ◽  
T Cell Responses ◽  
Antigen Presenting Cells ◽  
Cytotoxic T Cell ◽  
Cell Responses ◽  
Cytotoxic T Cell Responses ◽  
Antigen Presenting

Abstract Several cell-based immunotherapy strategies have been developed to specifically modulate T cell–mediated immune responses. These methods frequently rely on the utilization of tolerogenic cell–based antigen-presenting cells (APCs). However, APCs are highly sensitive to cytotoxic T-cell responses, thus limiting their therapeutic capacity. Here, we describe a novel bead-based approach to modulate T-cell responses in an antigen-specific fashion. We have generated killer artificial APCs (κaAPCs) by coupling an apoptosis-inducing α-Fas (CD95) IgM mAb together with HLA-A2 Ig molecules onto beads. These κaAPCs deplete targeted antigen-specific T cells in a Fas/Fas ligand (FasL)–dependent fashion. T-cell depletion in cocultures is rapidly initiated (30 minutes), dependent on the amount of κaAPCs and independent of activation-induced cell death (AICD). κaAPCs represent a novel technology that can control T cell–mediated immune responses, and therefore has potential for use in treatment of autoimmune diseases and allograft rejection.

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 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 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 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.

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 HIV mRNA Vaccines—Progress and Future Paths

Vaccines ◽  
2021 ◽  
Vol 9 (2) ◽  
pp. 134
Author(s):  
Zekun Mu ◽  
Barton F. Haynes ◽  
Derek W. Cain
Keyword(s):  
T Cell ◽  
Neutralizing Antibodies ◽  
Vaccination Strategy ◽  
T Cell Responses ◽  
Neutralizing Antibody ◽  
Cytotoxic T Cell ◽  
Therapeutic Vaccines ◽  
Cell Responses ◽  
Broadly Neutralizing Antibody ◽  
Cytotoxic T Cell Responses

The SARS-CoV-2 pandemic introduced the world to a new type of vaccine based on mRNA encapsulated in lipid nanoparticles (LNPs). Instead of delivering antigenic proteins directly, an mRNA-based vaccine relies on the host’s cells to manufacture protein immunogens which, in turn, are targets for antibody and cytotoxic T cell responses. mRNA-based vaccines have been the subject of research for over three decades as a platform to protect against or treat a variety of cancers, amyloidosis and infectious diseases. In this review, we discuss mRNA-based approaches for the generation of prophylactic and therapeutic vaccines to HIV. We examine the special immunological hurdles for a vaccine to elicit broadly neutralizing antibodies and effective T cell responses to HIV. Lastly, we outline an mRNA-based HIV vaccination strategy based on the immunobiology of broadly neutralizing antibody development.

Melanocyte-specific, cytotoxic T cell responses in vitiligo: the effective variant of melanoma immunity?

2005 ◽  
Vol 18 (4) ◽  
pp. 234-242 ◽  
Author(s):  
Silvia Garbelli ◽  
Stefania Mantovani ◽  
Belinda Palermo ◽  
Claudia Giachino
Keyword(s):  
T Cell ◽  
T Cell Responses ◽  
Cytotoxic T Cell ◽  
Cell Responses ◽  
Cytotoxic T Cell Responses

Cytotoxic T Cell Responses against Mesothelioma by Apoptotic Cell-pulsed Dendritic Cells

2004 ◽  
Vol 169 (12) ◽  
pp. 1322-1330 ◽  
Author(s):  
Frédéric Ebstein ◽  
Carole Sapede ◽  
Pierre-Joseph Royer ◽  
Marie Marcq ◽  
Catherine Ligeza-Poisson ◽  
...  
Keyword(s):  
Dendritic Cells ◽  
T Cell ◽  
Apoptotic Cell ◽  
T Cell Responses ◽  
Cytotoxic T Cell ◽  
Cell Responses ◽  
Cytotoxic T Cell Responses
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