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.

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.

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.

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 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 Immunogenicity and Cross-Reactivity of Rhesus Adenoviral Vectors

2018 ◽  
Vol 92 (11) ◽  
Author(s):  
M. Justin Iampietro ◽  
Rafael A. Larocca ◽  
Nicholas M. Provine ◽  
Peter Abbink ◽  
Zi Han Kang ◽  
...  
Keyword(s):  
T Cell ◽  
Neutralizing Antibodies ◽  
Vaccine Development ◽  
T Cell Responses ◽  
Adenoviral Vectors ◽  
Cross Reactivity ◽  
Human Populations ◽  
Humoral Immune ◽  
Cell Responses ◽  
The Impact

ABSTRACT Adenovirus (Ad) vectors are being investigated as vaccine candidates, but baseline antivector immunity exists in human populations to both human Ad (HuAd) and chimpanzee Ad (ChAd) vectors. In this study, we investigated the immunogenicity and cross-reactivity of a panel of recently described rhesus adenoviral (RhAd) vectors. RhAd vectors elicited T cells with low exhaustion markers and robust anamnestic potential. Moreover, RhAd vector immunogenicity was unaffected by high levels of preexisting anti-HuAd immunity. Both HuAd/RhAd and RhAd/RhAd prime-boost vaccine regimens were highly immunogenic, despite a degree of cross-reactive neutralizing antibodies (NAbs) between phylogenetically related RhAd vectors. We observed extensive vector-specific cross-reactive CD4 T cell responses and more limited CD8 T cell responses between RhAd and HuAd vectors, but the impact of vector-specific cellular responses was far less than that of vector-specific NAbs. These data suggest the potential utility of RhAd vectors and define novel heterologous prime-boost strategies for vaccine development. IMPORTANCE To date, most adenoviral vectors developed for vaccination have been HuAds from species B, C, D, and E, and human populations display moderate to high levels of preexisting immunity. There is a clinical need for new adenoviral vectors that are not hindered by preexisting immunity. Moreover, the development of RhAd vector vaccines expands our ability to vaccinate against multiple pathogens in a population that may have received other HuAd or ChAd vectors. We evaluated the immunogenicity and cross-reactivity of RhAd vectors, which belong to the poorly described adenovirus species G. These vectors induced robust cellular and humoral immune responses and were not hampered by preexisting anti-HuAd vector immunity. Such properties make RhAd vectors attractive as potential vaccine vectors.

Generation of Cytotoxic T Cell Responses Directed to HLA Class I Restricted Epitopes from the Aspergillus f16 Allergen.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 1644-1644
Author(s):  
Gamal Ramadan ◽  
Barbara Davies ◽  
Viswanath P. Kurup ◽  
Carolyn A. Keever-Taylor
Keyword(s):  
T Cells ◽  
T Cell ◽  
Cd8 T Cells ◽  
Cell Response ◽  
T Cell Responses ◽  
Peptide Pool ◽  
Hla Class I ◽  
T Cell Response ◽  
Class I ◽  
Cell Responses

Abstract Invasive pulmonary aspergillosis is a primary cause of morbidity and mortality in immunocompromised patients such as hematopoietic progenitor cell transplant patients. Studies both in patients with allergic bronchopulmonary aspergillosis and murine models demonstrated the importance of a CD4+ Th1 T cell response in conferring protection from infection or preventing disease progression. The role of CD8+ T cell response to A. fumigatus is less clear. Our efforts to develop effective immunotherapeutic approaches against A. fumigatus included preparation of 104 overlapping pentadecapeptides spanning the 427 aa coding region of the aspergillus allergen, Asp f16 previously shown to induce T cell responses. Each 15 aa peptide overlaps the preceding peptide by 11 aa. Monocytes from healthy donors were treated with GM-CSF and IL-4 for 2-3 days to generate immature dendritic cells (fast DC), pulsed with a pool containing 1 μg of each pentadecapeptide, then matured with inflammatory cytokines (IL-1β, IL-6, PGE2 and TNF-alpha) for 2 days. Mature, pulsed fast DC were used to prime proliferative and CTL responses (weekly primings). T cells from 5/5 donors proliferated to the peptide pool. CTL lines were obtained from each of the first two donors that were primed. After 4 weeks the line from donor #2 was strongly cytotoxic to autologous peptide pool-pulsed and aspergillus culture extract-pulsed DC and peptide pool pulsed HLA Class I matched BLCL. Supernatant from this line killed fresh aspergillus conidia. Six of 21 smaller pools of 4-11 peptides showed reactivity. Specificity could be narrowed by screening peptides shared by the pools to 3 candidate peptides. Pool-pulsed BLCL matched for only 1 or 2 HLA alleles were used to demonstrate CTL restriction by HLA-B-3501. A database search of peptides likely to be restricted to B3501 identified the likely sequences as YFKYTAAAL, LPLCSAQTW, and GTRFPQTPM. Each induced similar reactivity when pulsed onto B-3501+ targets. CD8+ T cells steadily increased from 5.2% at week 3 to 19.0% after the 7th priming. CTL activity and IFNγ production were exclusively mediated by CD8+ T cells and CD107a was expressed by 42% of the CD8+ T cells in response to pool-pulsed BLCL indicating degranulation. CTL cross-reacted with pool pulsed B3503+ BLCL but not B3502+, or B3508+ BLCL. B3503+ BLCL presented YFKYTAAAL and to a lesser extent GTRFPQTPM but not peptide LPLCSAQTW. Our data show that DC pulsed with a pentadecapeptide pool from Asp f16 are capable of inducing a CD8+, HLA-Class I restricted Aspergillus-specific T cell response directed to multiple peptides contained within the pool. Further characterization of this system is in progress to identify additional immunogenic peptides from Asp f16 that might be useful in clinical immunotherapy protocols to prime protective immune responses to prevent or treat aspergillus infection.

A simple and efficient method for the monitoring of antigen-specific T cell responses using peptide pool arrays in a modified ELISpot assay

2001 ◽  
Vol 254 (1-2) ◽  
pp. 59-66 ◽  
Author(s):  
Timothy W Tobery ◽  
Su Wang ◽  
Xin-Min Wang ◽  
Michael P Neeper ◽  
Kathrin U Jansen ◽  
...  
Keyword(s):  
T Cell ◽  
Efficient Method ◽  
Elispot Assay ◽  
T Cell Responses ◽  
Peptide Pool ◽  
Cell Responses
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