scholarly journals IL-2 and IFN-[gamma] are biomarkers of SARS-CoV-2 specific cellular response in whole blood stimulation assays

2021 ◽  
Author(s):  
Begona Perez-Cabezas ◽  
Ricardo Ribeiro ◽  
Ines Costa ◽  
Sofia Esteves ◽  
Ana Rafaela Teixeira ◽  
...  
Keyword(s):  
Whole Blood ◽  
Cellular Response ◽  
Stimulation Index ◽  
Interleukin 2 ◽  
Cellular Responses ◽  
Cell Responses ◽  
Cellular Immune Responses ◽  
Ifn Γ ◽  
Cellular Immune ◽  
Whole Blood Stimulation

Objectives: A proper description of the immune response to SARS-CoV-2 will be critical for the assessment of protection elicited after both infection and vaccination. Uncoupled T and B cell responses have been described in acute and convalescent patients and exposed individuals. We aimed to assess the potential usefulness of whole blood stimulation assays to identify functional cellular immune responses to SARS-CoV-2. Methods: Blood from COVID-19 recovered individuals (5 months after infection) and negative subjects was stimulated for 24 hours with HLA predicted peptide megapools of the Spike and Nucleoprotein, or the mixture of them. After stimulation, cytokines were quantified using a beads-based multiplex assay. Results: Interleukin-2 and IFN-γ were found to be specific biomarkers of SARS-CoV-2 cellular response. Using the Spike and Nucleoprotein mixture, 91.3% of COVID-19 recovered individuals presented an IL-2 stimulation index over the cut-off, while 82.6% showed IFN-γ. All the negative individuals presented an IL-2 response under the cut-off, while 5.3% of these subjects presented positive IFN-γ stimulation indexes. Moreover, IL-2 production correlated with IgG levels for Spike 1, RBD, and Nucleocapsid. Conclusion: We demonstrate the potential of whole blood stimulation assays and the quantification of IL-2 and IFN-γ for the analysis of SARS-CoV-2 functional cellular responses.

scholarly journals Humoral and Cellular Immune Responses to Trypanosoma cruzi-Derived Paraflagellar Rod Proteins in Patients with Chagas' Disease

2003 ◽  
Vol 71 (6) ◽  
pp. 3165-3171 ◽  
Author(s):  
Vladimir Michailowsky ◽  
Keith Luhrs ◽  
Manoel Otávio C. Rocha ◽  
David Fouts ◽  
Ricardo T. Gazzinelli ◽  
...  
Keyword(s):  
Trypanosoma Cruzi ◽  
Immune Responses ◽  
Chagas Disease ◽  
Mononuclear Cells ◽  
Clinical Symptoms ◽  
Cellular Responses ◽  
Peripheral Blood Mononuclear ◽  
Cellular Immune Responses ◽  
Ifn Γ ◽  
Cellular Immune

ABSTRACT Sera and peripheral blood mononuclear cells (PBMC) from patients displaying different clinical symptoms as well as from normal uninfected individuals (NI) were used to evaluate the humoral and cellular responses of Chagas' disease patients to Trypanosoma cruzi-derived paraflagellar rod proteins (PFR). Our results show that sera from both asymptomatic Chagas' disease patients (ACP) and cardiac Chagas' disease patients (CCP) have higher levels of antibodies to PFR than sera from NI. Immunoglobulin G1 (IgG1) and IgG3 were the main Ig isotypes that recognized PFR. We also tested three recombinant forms of PFR, named rPAR-1, rPAR-2, and rPAR-3, by Western blot analysis. Sera from seven out of eight patients with Chagas' disease recognized one of the three rPAR forms. Sera from 75, 50, and 37.5% of Chagas' disease patients tested recognized rPAR-3, rPAR-2, and rPAR-1, respectively. PFR induced proliferation of 100 and 70% of PBMC from ACP and CCP, respectively. Further, stimulation of cells from Chagas' disease patients with PFR enhanced the frequencies of both small and large CD4+ CD25+ and CD4+ CD69+ lymphocytes, as well as that of small CD8+ CD25+ lymphocytes. Finally, we evaluated the ability of PFR to elicit the production of gamma interferon (IFN-γ) by PBMC from patients with Chagas' disease. Fifty percent of the PBMC from ACP as well as CCP produced IFN-γ upon stimulation with PFR. PFR enhanced the percentages of IFN-γ-producing cells in both CD3+ and CD3− populations. Within the T-cell population, large CD4+ T lymphocytes were the main source of IFN-γ.

scholarly journals Magnitude and Phenotype of Cellular Immune Responses Elicited by Recombinant Adenovirus Vectors and Heterologous Prime-Boost Regimens in Rhesus Monkeys

2008 ◽  
Vol 82 (10) ◽  
pp. 4844-4852 ◽  
Author(s):  
Jinyan Liu ◽  
Bonnie A. Ewald ◽  
Diana M. Lynch ◽  
Matthew Denholtz ◽  
Peter Abbink ◽  
...  
Keyword(s):  
Immune Responses ◽  
T Lymphocyte ◽  
Rhesus Monkeys ◽  
Recombinant Adenovirus ◽  
Interleukin 2 ◽  
Cellular Immune Responses ◽  
Tnf Α ◽  
Ifn Γ ◽  
Cellular Immune ◽  
Lymphocyte Responses

ABSTRACT Recombinant adenovirus serotype 5 (rAd5) vaccine vectors for human immunodeficiency virus type 1 (HIV-1) and other pathogens have been shown to elicit antigen-specific cellular immune responses. Rare serotype rAd vectors have also been constructed to circumvent preexisting anti-Ad5 immunity and to facilitate the development of novel heterologous rAd prime-boost regimens. Here we show that rAd5, rAd26, and rAd48 vectors elicit qualitatively distinct phenotypes of cellular immune responses in rhesus monkeys and can be combined as potent heterologous prime-boost vaccine regimens. While rAd5-Gag induced primarily gamma interferon-positive (IFN-γ+) and IFN-γ+/tumor necrosis factor alpha+ (TNF-α+) T-lymphocyte responses, rAd26-Gag and rAd48-Gag induced higher proportions of interleukin-2+ (IL-2+) and polyfunctional IFN-γ+/TNF-α+/IL-2+ T-lymphocyte responses. Priming with the rare serotype rAd vectors proved remarkably effective for subsequent boosting with rAd5 vectors. These data demonstrate that the rare serotype rAd vectors elicited T-lymphocyte responses that were phenotypically distinct from those elicited by rAd5 vectors and suggest the functional relevance of polyfunctional CD8+ and CD4+ T-lymphocyte responses. Moreover, qualitative differences in cellular immune responses may prove critical in determining the overall potency of heterologous rAd prime-boost regimens.

A MATHEMATICAL MODEL TO ASSESS THE IMMUNE RESPONSE AGAINSTTRYPANOSOMA CRUZIINFECTION

2015 ◽  
Vol 23 (01) ◽  
pp. 131-163 ◽  
Author(s):  
HYUN MO YANG
Keyword(s):  
Mathematical Model ◽  
Trypanosoma Cruzi ◽  
Immune Responses ◽  
Cellular Response ◽  
Humoral Response ◽  
Cellular Responses ◽  
Cellular Immune Responses ◽  
Trivial Equilibrium ◽  
Cellular Immune ◽  
Cruzi Infection

A mathematical model is developed to assess humoral and cellular immune responses against Trypanosoma cruzi infection. Analysis of the model shows a unique non-trivial equilibrium, which is locally asymptotically stable, except in the case of a strong cellular response. When the proliferation of the activated CD8 T cells is increased, this equilibrium becomes unstable and a limit cycle appears. However, this behavior can be avoided by increasing the action of the humoral response. Therefore, unbalanced humoral and cellular responses can be responsible for long asymptomatic period, and the control of Trypanosoma cruzi infection is a consequence of well coordinated action of both humoral and cellular responses.

scholarly journals CD4+T Cell Response Correlates with Naturally Acquired Antibodies against Plasmodium vivax Tryptophan-Rich Antigens

2015 ◽  
Vol 83 (5) ◽  
pp. 2018-2029 ◽  
Author(s):  
Mohammad Zeeshan ◽  
Kriti Tyagi ◽  
Yagya D. Sharma
Keyword(s):  
T Cell ◽  
Plasmodium Vivax ◽  
Cell Response ◽  
Interleukin 2 ◽  
T Cell Response ◽  
Content Type ◽  
Cellular Immune Responses ◽  
Large Numbers ◽  
Ifn Γ ◽  
Cellular Immune

Tryptophan-rich proteins play important biological functions for thePlasmodiumparasite.Plasmodium vivaxcontains remarkably large numbers of such proteins belonging to the “Pv-fam-a” family that need to be characterized. Earlier, we reported the presence of memory T cells and naturally acquired antibodies against 15 of these proteins inP. vivaxmalaria-exposed individuals (M. Zeeshan, H. Bora, and Y. D. Sharma, J Infect Dis207:175–185, 2013,http://dx.doi.org/10.1093/infdis/jis650). Here, we sought to characterize and ascertain the cross talk between effector responses of T and B cells in malarial patients against all Pv-fam-a family proteins. Therefore, we expressed the remaining 21 of these proteins inEscherichia coliand studied the humoral and cellular immune responses based on the same parameters used in our previous study. Naturally acquired IgG antibodies were detected against all 21 antigens inP. vivaxpatient sera (37.7 to 94.4% seropositivity). These antigens were able to activate the lymphocytes ofP. vivax-exposed individuals, and the activated CD4+T lymphocytes produced higher levels of Th1 (interleukin-2 [IL-2] and gamma interferon [IFN-γ]) and Th2 (IL-4 and IL-10) cytokines than the healthy controls, but the response was Th2 biased. The combined results of present and previous studies seem to suggest a striking link between induction of the CD4+T cell response and naturally acquired antibodies against all 36 proteins of the Pv-fam-a family, the majority of them having conserved sequences in the parasite population. Further work is required to utilize this information to develop immunotherapeutic treatments for this disease.

scholarly journals A DNA Vaccine Encoding Lumazine Synthase from Brucella abortus Induces Protective Immunity in BALB/c Mice

2002 ◽  
Vol 70 (5) ◽  
pp. 2507-2511 ◽  
Author(s):  
Carlos A. Velikovsky ◽  
Juliana Cassataro ◽  
Guillermo H. Giambartolomei ◽  
Fernando A. Goldbaum ◽  
Silvia Estein ◽  
...  
Keyword(s):  
Brucella Abortus ◽  
Protective Immunity ◽  
Cellular Response ◽  
Interleukin 2 ◽  
Humoral Response ◽  
Control Groups ◽  
Cellular Immune Responses ◽  
Lumazine Synthase ◽  
Cellular Immune

ABSTRACT This study was conducted to evaluate the immunogenicity of the Brucella abortus lumazine synthase (BLS) gene cloned into the pcDNA3 plasmid, which is driven by the cytomegalovirus promoter. Injection of plasmid DNA carrying the BLS gene (pcDNA-BLS) into BALB/c mice elicited both humoral and cellular immune responses. Antibodies to the encoded BLS included immunoglobulin G1 (IgG1) IgG2a, IgG2b, IgG3, and IgM isotypes. Animals injected with pcDNA-BLS exhibited a dominance of IgG2a over IgG1. In addition, spleen cells from vaccinated animals produced interleukin-2 and gamma interferon but not IL-10 or IL-4 after in vitro stimulation with recombinant BLS (rBLS), suggesting the induction of a Th1 response. Protection was evaluated by comparing the levels of infection in the spleens of vaccinated mice challenged with B. abortus 544. Immunization with pcDNA-BLS- reduced the bacterial burden relative to those in the control groups. Mice immunized with rBLS produced a significant humoral response but did not show a specific cellular response or any protection from challenge. Altogether, these data suggest that pcDNA-BLS is a good immunogen for the production of humoral and cell-mediated responses in mice and is a candidate for use in future studies of vaccination against brucellosis.

scholarly journals Priming of Human Papillomavirus Type 11-Specific Humoral and Cellular Immune Responses in College-Aged Women with a Virus-Like Particle Vaccine

2002 ◽  
Vol 76 (15) ◽  
pp. 7832-7842 ◽  
Author(s):  
Rebecca T. Emeny ◽  
Cosette M. Wheeler ◽  
Kathrin U. Jansen ◽  
William C. Hunt ◽  
Tong-Ming Fu ◽  
...  
Keyword(s):  
Human Papillomavirus ◽  
Immune Responses ◽  
Antibody Titer ◽  
Mononuclear Cells ◽  
Geometric Mean ◽  
Interleukin 2 ◽  
Cellular Immune Responses ◽  
Virus Like Particle ◽  
Ifn Γ ◽  
Cellular Immune

ABSTRACT In this study, we evaluated the potency of a human papillomavirus (HPV) virus-like particle (VLP)-based vaccine at generating HPV type 11 (HPV-11)-specific cellular and humoral immune responses in seronegative women. The vaccine was administered by intramuscular immunizations at months 0, 2, and 6. A fourth immunization was administered to approximately half of the women at month 12. All vaccine recipients had positive HPV-11 VLP-specific lymphoproliferative responses at month 3 following the second immunization (geometric mean lymphoproliferative stimulation index [SI] = 28.4; 95% confidence interval [CI] = 16.9 to 48.0) and HPV-11 VLP-specific antibody titers following the first immunization at month 1 (geometric mean antibody titer = 53.9 milli-Merck units/ml, 95% CI, 34.8 to 83.7). In contrast, lymphoproliferative and antibody titer responses were never detected in the participants who received placebo. Relatively homogeneous lymphoproliferative responses were observed in all vaccinated women. The mean lymphoproliferative SI of the vaccinated group over the first 12 months of the study was 7.6-fold greater than that of the placebo group following the initial immunization. The cellular immune responses generated by VLP immunization were both Th1 and Th2, since peripheral blood mononuclear cells from vaccinees, but not placebo recipients, secreted interleukin 2 (IL-2), IL-5, and gamma interferon (IFN-γ) in response to in vitro stimulation with HPV-11 VLP. The proliferation-based SI was moderately correlated with IFN-γ production and significantly correlated with IL-2 production after the third immunization (P = 0.078 and 0.002, respectively). The robust lymphoproliferative responses were specific for HPV-11, since SIs generated against bovine papillomavirus and HPV-16 VLPs were not generally observed and when detected were similar pre- and postimmunization.

scholarly journals Plasmodium falciparum-Specific Cellular Immune Responses after Immunization with the RTS,S/AS02D Candidate Malaria Vaccine in Infants Living in an Area of High Endemicity in Mozambique

2009 ◽  
Vol 77 (10) ◽  
pp. 4502-4509 ◽  
Author(s):  
Arnoldo Barbosa ◽  
Denise Naniche ◽  
John J. Aponte ◽  
M. Nelia Manaca ◽  
Inacio Mandomando ◽  
...  
Keyword(s):  
Immune Responses ◽  
Malaria Vaccine ◽  
Interleukin 2 ◽  
Vaccine Trial ◽  
Field Studies ◽  
Clinical Phase ◽  
Cellular Immune Responses ◽  
Ifn Γ ◽  
Cellular Immune ◽  
First Time

ABSTRACT Results from clinical trials in areas where malaria is endemic have shown that immunization with RTS,S/AS02A malaria vaccine candidate induces partial protection in adults and children and cellular effector and memory responses in adults. For the first time in a malaria vaccine trial, we sought to assess the cell-mediated immune responses to RTS,S antigen components in infants under 1 year of age participating in a clinical phase I/IIb trial of RTS,S/AS02D in Mozambique. Circumsporozoite protein (CSP)-specific responses were detected in approximately half of RTS,S-immunized infants and included gamma interferon (IFN-γ), interleukin-2 (IL-2), and combined IL-2/IL-4 responses. The median stimulation indices of cytokine-producing CD4+ and CD8+ cells were very low but significantly higher in RTS,S-immunized infants than in infants that received the comparator vaccine. Protection against subsequent malarial infection tended to be associated with a higher percentage of individuals with CSP-specific IL-2 in the supernatant (P = 0.053) and with higher CSP-specific IFN-γ-producing CD8+ T-cell responses (P = 0.07). These results report for the first time the detection of malaria-specific cellular immune responses after vaccination of infants less than 1 year of age and pave the way for future field studies of cellular immunity to malaria vaccine candidates.

scholarly journals Cytokine Profiles from Antigen-Stimulated Whole-Blood Samples among Patients with Pulmonary or Nonmeningeal Disseminated Coccidioidomycosis

2015 ◽  
Vol 22 (8) ◽  
pp. 917-922 ◽  
Author(s):  
Neil M. Ampel ◽  
Lance A. Nesbit ◽  
Chinh T. Nguyen ◽  
Suzette Chavez ◽  
Kenneth S. Knox ◽  
...  
Keyword(s):  
Immune Response ◽  
Whole Blood ◽  
Cellular Immune Response ◽  
Interleukin 2 ◽  
Blood Samples ◽  
Acute Pneumonia ◽  
Ifn Γ ◽  
Whole Blood Samples ◽  
Disseminated Disease ◽  
Cellular Immune

ABSTRACTThe outcome of coccidioidomycosis depends on a robust specific cellular immune response. A T-helper type 1 (Th1) cellular immune response has been previously associated with resolution of clinical illness. However, the precise elements of this response and whether cytokines not involved with the Th1 response play a role in coccidioidomycosis are not known. Whole-blood samples were obtained from subjects with active coccidioidomycosis and controls and incubated for 18 h with T27K, a coccidioidal antigen preparation. The supernatant was then assayed for gamma interferon (IFN-γ), interleukin-2 (IL-2), tumor necrosis factor alpha (TNF-α), IL-4, IL-6, IL-10, and IL-17A. A total of 43 subjects, 16 with acute pneumonia, 9 with pulmonary sequelae of nodules and cavities, and 18 with nonmeningeal disseminated coccidioidomycosis, were studied. Compared to concentrations in healthy immune and nonimmune donors, the median concentration of IL-17A was significantly higher in those with active coccidioidomycosis (for both,P< 0.01). In addition, IL-6 concentrations were higher while IL-2 and IFN-γ concentrations were significantly lower in those with nonmeningeal disseminated disease diagnosed within 12 months than in those with acute pneumonia (for all,P< 0.05). The cytokine profile among patients with active coccidioidomycosis is distinct in that IL-17A is persistently present. In addition, those with nonmeningeal disseminated disease have an increased inflammatory cytokine response and diminished Th1 responses that modulate over time.

scholarly journals Comparison of Plasmid Vaccine Immunization Schedules Using IntradermalIn VivoElectroporation

2011 ◽  
Vol 18 (9) ◽  
pp. 1577-1581 ◽  
Author(s):  
David Hallengärd ◽  
B. Kristian Haller ◽  
Anna-Karin Maltais ◽  
Eva Gelius ◽  
Kopek Nihlmark ◽  
...  
Keyword(s):  
Immune Responses ◽  
Transfection Efficiency ◽  
Short Interval ◽  
Interleukin 2 ◽  
Cellular Immune Responses ◽  
Plasmid Vaccine ◽  
Ifn Γ ◽  
Plasmid Transfection ◽  
Cellular Immune

ABSTRACTIn vivoelectroporation (EP) has proven to significantly increase plasmid transfection efficiency and to augment immune responses after immunization with plasmids. In this study, we attempted to establish an immunization protocol using intradermal (i.d.) EP. BALB/c mice were immunized with a plasmid encoding HIV-1 p37Gag, either i.d. with the Derma Vax EP device, intramuscularly (i.m.) without EP, or with combinations of both. A novel FluoroSpot assay was used to evaluate the vaccine-specific cellular immune responses. The study showed that i.d. EP immunizations induced stronger immune responses than i.m. immunizations using a larger amount of DNA and that repeated i.d. EP immunizations induced stronger immune responses than i.m. priming followed by i.d. EP boosting. Two and three i.d. EP immunizations induced immune responses of similar magnitude, and a short interval between immunizations was superior to a longer interval in terms of the magnitude of cellular immune responses. The FluoroSpot assay allowed for the quantification of vaccine-specific cells secreting either gamma interferon (IFN-γ), interleukin-2 (IL-2), or both, and the sensitivity of the assay was confirmed with IFN-γ and IL-2 enzyme-linked immunosorbent spot (ELISpot) assays. The data obtained in this study can aid in the design of vaccine protocols using i.d. EP, and the results emphasize the advantages of the FluoroSpot assay over traditional ELISpot assay and intracellular staining for the detection and quantification of bifunctional vaccine-specific immune responses.

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