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1.
Cell Rep Med ; 4(1): 100904, 2023 Jan 17.
Artigo em Inglês | MEDLINE | ID: mdl-36652913

RESUMO

Particulate adjuvants are key components of many approved vaccines, but their mechanism of adjuvanticity is debated. Muñoz-Wolf et al.1 find that 50-nm particles maximize cell-mediated immune responses by activating the caspase-11 inflammasome, providing mechanistic insight to particulate adjuvant technologies.


Assuntos
Inflamassomos , Proteína 3 que Contém Domínio de Pirina da Família NLR , Inflamassomos/metabolismo , Proteínas de Transporte , Adjuvantes Imunológicos , Imunidade Celular
2.
Adv Exp Med Biol ; 1394: 51-72, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36587381

RESUMO

Major advances have been made in our understanding of CNS tumors, especially glioma, however, the survival of patients with malignant glioma remains poor. While radiation and chemotherapy have increased overall survival, glioblastoma multiforme (GBM) still has one of the worst 5-year survival rates of all human cancers. Here, in this chapter, the authors review the abrogation of the immune system in the tumor setting, revealing many plausible targets for therapy and the current immunotherapy treatment strategies employed. Notably, glioma has also been characterized as a subset of primary spinal cord tumor and current treatment recommendations are outlined here.


Assuntos
Neoplasias Encefálicas , Glioblastoma , Glioma , Neoplasias da Medula Espinal , Humanos , Neoplasias Encefálicas/terapia , Neoplasias Encefálicas/patologia , Neoplasias da Medula Espinal/patologia , Glioblastoma/patologia , Imunoterapia , Encéfalo/patologia , Imunidade Adaptativa , Imunidade Celular
4.
Int J Biol Macromol ; 227: 576-589, 2023 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-36549613

RESUMO

Nanoparticles targeting the DEC-205 receptor were found to induce antigen-specific protective immune response. When the delivery system carries both antigens and immunomodulators, it can maximize the expected therapeutic effect of the drug and induce effective humoral and cellular immune responses to antigens.In this study, we encapsulated the Eucommia ulmoides Oliv. polysaccharides (EUPS) into PLGA nanoparticles (NPs) and conjugated it with anti-CD205 monoclonal Ab (MAb) to produce a DEC-205 receptor targeted PLGA nanoparticles (anti-DEC-205-EUPS-PLGA NPs). The physicochemical characteristics and adjuvant activity of the above NPs were evaluated in vitro and in vivo. In the in vitro setting, 200 µg·mL-1 anti-DEC-205-EUPS-PLGA could improve the proliferation of DCs and promote their antigen up-take activity. In the in vivo setting, anti-DEC-205-EUPS-PLGA NPs remarkably controlled the release of drug and antigen to induce sustained immune responses and up-regulated the levels of FMDV-specific IgG antibodies, promoted the cytotoxic activity of CTLs and NK cells, and improved the proliferation of splenocytes. Moreover, the anti-DEC-205-EUPS-PLGA NPs facilitated the maturation of DCs. The above data indicated that anti-DEC-205-EUPS-PLGA NPs employed as an targeted adjuvant induced the humoral and cellular immune activity by promoting the maturation of DCs. These findings may provide a new insight onto the development of vaccine adjuvants.


Assuntos
Eucommiaceae , Febre Aftosa , Nanopartículas , Vacinas , Animais , Camundongos , Copolímero de Ácido Poliláctico e Ácido Poliglicólico/farmacologia , Glicóis , Células Dendríticas , Antígenos , Imunidade Celular , Adjuvantes Imunológicos/farmacologia , Polissacarídeos/farmacologia
5.
J Med Virol ; 95(1): e28380, 2023 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-36478357

RESUMO

Children are the high-risk group for COVID-19, and in need of vaccination. However, humoral and cellular immune responses of COVID-19 vaccine remain unclear in vaccinated children. To establish the rational immunization strategy of inactivated COVID-19 vaccine for children, the immunogenicity of either one dose or two doses of the vaccine in children was evaluated. A prospective cohort study of 322 children receiving inactivated COVID-19 vaccine was established in China. The baseline was conducted after 28 days of the first dose, and the follow-up was conducted after 28 days of the second dose. The median titers of receptor binding domain (RBD)-IgG, and neutralizing antibody (NAb) against prototype strain and Omicron variant after the second dose increased significantly compared to those after the first dose (first dose: 70.0, [interquartile range, 30.0-151.0] vs. second dose: 1261.0 [636.0-2060.0] for RBD-IgG; 2.5 [2.5-18.6] vs. 252.0 [138.6-462.1] for NAb against prototype strain; 2.5 [2.5-2.5] vs. 15.0 [7.8-26.5] for NAb against Omicron variant, all p < 0.05). The flow cytometry results showed that the first dose elicited SARS-CoV-2 specific cellular immunity, while the second dose strengthened SARS-CoV-2 specific IL-2+ or TNF-α+  monofunctional, IFN-γ+ TNF-α+  bifunctional, and IFN-γ- IL-2+ TNF-α+ multifunctional CD4+ T cell responses (p < 0.05). Moreover, SARS-CoV-2 specific memory T cells were generated after the first vaccination, including the central memory T cells and effector memory T cells. The present findings provide scientific evidence for the vaccination strategy of the inactive vaccines among children against COVID-19 pandemic.


Assuntos
Vacinas contra COVID-19 , COVID-19 , Criança , Humanos , Interleucina-2 , Pandemias , Estudos Prospectivos , Fator de Necrose Tumoral alfa , COVID-19/prevenção & controle , SARS-CoV-2 , Vacinação , Imunidade Celular , Anticorpos Neutralizantes , Imunoglobulina G , Anticorpos Antivirais , Imunidade Humoral
6.
Balkan Med J ; 40(1): 34-39, 2023 01 23.
Artigo em Inglês | MEDLINE | ID: mdl-36484365

RESUMO

Background: The coronavirus disease 2019 vaccine induces both antibody and T-cell immune responses and has been proven to be effective in preventing coronavirus disease 2019, including its severe disease form, in healthy individuals. However, the details of severe acute respiratory syndrome coronavirus-2 immunoglobulin-G antibody responses and severe acute respiratory syndrome coronavirus-2 specific T-cell responses in patients with sarcoidosis are unknown. Aim: To measure and compare antibody responses and T cell responses using enzyme-linked immunosorbent assays and interferon-gamma release assay in sarcoidosis patients infected with coronavirus disease 2019 and vaccinated with CoronaVac. Study Design: A prospective cohort study. Methods: A total of 28 coronavirus disease 2019 polymerase chain reaction test-positive sarcoidosis patients who were infected with severe acute respiratory syndrome coronavirus-2 in the past 6 months and did not have coronavirus disease 2019 vaccination and 28 sarcoidosis patients who were administered with 2 doses of CoronaVac and never had coronavirus disease 2019 were included in this study. The immune response levels of patients were determined by measuring the severe acute respiratory syndrome coronavirus-2 immunglobulinG and interferon-gamma levels in the blood of the patients by the enzyme-linked immunosorbent assays method and interferon-gamma release assay tests, respectively. Results: The mean age of the patients in the COVID-infected group was 48.1 ± 11.3, while the mean age of the patients in the vaccinated group was 55.6 ± 9.32. The mean time elapsed after infection was 97.32 ± 42.1 days, while 61.3 ± 28.7 days had passed since the second vaccination dose. In the COVID-infected group, immunoglobulin-G and interferon-gamma release tests were positive in 64.3% and 89.3% of the patients, respectively. In the vaccinated group, immunoglobulin-G was positive in 10.7% of the patients, and interferon-gamma release test was positive in 14.3%. Conclusion: Innate immune responses are better than adaptive immune responses in patients with sarcoidosis. The coronaVac vaccine is insufficient to generate humoral and cellular immunities in patients with sarcoidosis.


Assuntos
Vacinas contra COVID-19 , COVID-19 , Imunidade Celular , Imunidade Humoral , Sarcoidose , Humanos , Anticorpos Antivirais , COVID-19/prevenção & controle , Vacinas contra COVID-19/imunologia , Imunoglobulina G , Estudos Prospectivos , SARS-CoV-2 , Vacinação , Adulto , Pessoa de Meia-Idade
7.
Clin Immunol ; 246: 109209, 2023 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-36539107

RESUMO

Children infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) develop less severe coronavirus disease 2019 (COVID-19) than adults. The mechanisms for the age-specific differences and the implications for infection-induced immunity are beginning to be uncovered. We show by longitudinal multimodal analysis that SARS-CoV-2 leaves a small footprint in the circulating T cell compartment in children with mild/asymptomatic COVID-19 compared to adult household contacts with the same disease severity who had more evidence of systemic T cell interferon activation, cytotoxicity and exhaustion. Children harbored diverse polyclonal SARS-CoV-2-specific naïve T cells whereas adults harbored clonally expanded SARS-CoV-2-specific memory T cells. A novel population of naïve interferon-activated T cells is expanded in acute COVID-19 and is recruited into the memory compartment during convalescence in adults but not children. This was associated with the development of robust CD4+ memory T cell responses in adults but not children. These data suggest that rapid clearance of SARS-CoV-2 in children may compromise their cellular immunity and ability to resist reinfection.


Assuntos
COVID-19 , Humanos , Adulto , SARS-CoV-2 , Linfócitos T CD4-Positivos , Imunidade Celular , Ativação Linfocitária , Anticorpos Antivirais
8.
Front Immunol ; 13: 1036680, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36466826

RESUMO

Objective: Recent research has shown that Parkin, an E3 ubiquitin ligase, modulates peripheral immune cells-mediated immunity during experimental autoimmune encephalomyelitis (EAE). Because the PTEN-induced putative kinase 1 (PINK1) protein acts upstream of Parkin in a common mitochondrial quality control pathway, we hypothesized that the systemic deletion of PINK1 could also modify the clinical course of EAE, altering the peripheral and central nervous systems' immune responses. Methods: EAE was induced in female PINK1-/- mice of different age groups by immunization with myelin oligodendrocyte glycoprotein peptide. Results: Compared to young wild-type controls, PINK1-/- mice showed earlier disease onset, albeit with a slightly less severe disease, while adult PINK1-/- mice displayed early onset and more severe acute symptoms than controls, showing persistent disease during the recovery phase. In adult mice, EAE severity was associated with significant increases in frequency of dendritic cells (CD11C+, IAIE+), lymphocytes (CD8+), neutrophils (Ly6G+, CD11b+), and a dysregulated cytokine profile in spleen. Furthermore, a massive macrophage (CD68+) infiltration and microglia (TMEM119+) and astrocyte (GFAP+) activation were detected in the spinal cord of adult PINK1-/- mice. Conclusions: PINK1 plays an age-related role in modulating the peripheral inflammatory response during EAE, potentially contributing to the pathogenesis of neuroinflammatory and other associated conditions.


Assuntos
Encefalomielite Autoimune Experimental , Feminino , Camundongos , Animais , Encefalomielite Autoimune Experimental/genética , Camundongos Knockout , Glicoproteína Mielina-Oligodendrócito , Imunidade Celular , Proteínas Quinases
9.
Front Cell Infect Microbiol ; 12: 1026457, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36467726

RESUMO

The association between periodontal disease and systemic disease has become a research hotspot. Porphyromonas gingivalis (P. gingivalis), a crucial periodontal pathogen, affects the development of systemic diseases. The pathogenicity of P. gingivalis is largely linked to interference with the host's immunity. This review aims to discover the role of P. gingivalis in the modulation of the host's adaptive immune system through a large number of virulence factors and the manipulation of cellular immunological responses (mainly mediated by T cells). These factors may affect the cause of large numbers of systemic diseases, such as atherosclerosis, hypertension, adverse pregnancy outcomes, inflammatory bowel disease, diabetes mellitus, non-alcoholic fatty liver disease, rheumatoid arthritis, and Alzheimer's disease. The point of view of adaptive immunity may provide a new idea for treating periodontitis and related systemic diseases.


Assuntos
Doença de Alzheimer , Doenças Periodontais , Feminino , Gravidez , Humanos , Porphyromonas gingivalis , Imunidade Celular , Imunidade Adaptativa
10.
Probl Radiac Med Radiobiol ; 27: 324-340, 2022 Dec.
Artigo em Inglês, Ucraniano | MEDLINE | ID: mdl-36582098

RESUMO

OBJECTIVE: to establish cellular immunity in clean-up workers of the Chornobyl accident compared to patients with malignant neoplasms of the oral cavity, oral and laryngeal parts of the pharynx according to the subpopulation organization of peripheral blood leukocytes. MATERIALS AND METHODS: We examined 112 males, age (56,92 ± 6,17) years (M ± SD), including 26 male clean-up workers exposed at the radiation dose 10-500 mSv; 20 male clean-up workers exposed at the dose range 504-990mSv; 33 patients with malignant neoplasms of the oral cavity, oral and laryngeal parts of the pharynx and 33 non-exposed subjects of the control group. Immune cell subsets analysis was performed by the expression of differential and activation antigens of peripheral blood leukocytes using flow cytometry. RESULTS: In assessing each group's cellular immunity, there was a decrease in the number of CD19+ B-lymphocytes, CD3+ HLA-DR+ T- and CD3- HLA-DR+ B-lymphocytes, CD3- 16+ 56+ natural killer cells, combined with an increase in the number of CD8+ T-lymphocytes. An increase in the relative number of CD4+ CD8+ T-lymphocytes was determined in clean-up workers (D < 500 mSv) and cancer patients. An increase in the number of CD8+ T-lymphocytes and a decrease in the number of CD4+ T-lymphocytes were observed in clean-up workers (D > 500 mSv), as well as in cancer patients. In addition, a decrease of monocytes, CD3+ 16+ 56+ , and CD3+ TCRαß+ T-lymphocytes was determined in patients with oncological pathology. CONCLUSIONS: The obtained results show the unidirectionality of changes in cellular immunity in the participants of the liquidation of the consequences of the accident at the Chornobyl nuclear power plant and patients with the investigated oncological pathology, which indicates the formation of persistent violations of antitumor protection in the participants of the liquidation of the consequences of the accident as the basis of oncogenesis. Determining changes in the number of lymphocytes, monocytes, granulocytes, CD4+ T-lymphocytes, CD4+ CD8+ immature T-lymphocytes, the immunoregulatory ratio CD4+ / CD8+, CD3+TCRαß+ T-lymphocytes and CD3+ 16+ 56+ CTL can have an additional effect on the effectiveness antitumor protection and the probability of oncogenesis risk in immunocompromised individuals.


Assuntos
Acidente Nuclear de Chernobyl , Imunidade Celular , Neoplasias Bucais , Neoplasias Faríngeas , Humanos , Masculino , Carcinogênese , Antígenos HLA-DR , Neoplasias Bucais/epidemiologia , Faringe , Pessoa de Meia-Idade , Neoplasias Faríngeas/epidemiologia
11.
Front Immunol ; 13: 1015525, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36569943

RESUMO

Introduction: Enzootic pneumonia still causes major economic losses to the intensive pig production. Vaccination against its primary pathogen, Mycoplasma hyopneumoniae, is carried out worldwide to control the disease and minimize clinical signs and performance losses. Nonetheless, the effects of both infection with, and vaccination against Mycoplasma hyopneumoniae on the innate and adaptive immune responses remain largely unknown. Therefore, we conducted a study in which piglets were injected once with a commercial bacterin V1 or V2, or the adjuvant of V1 (A) to investigate their effect on local, innate and adaptive immune responses. Methods: Three weeks after vaccination, piglets were challenge infected with M. hyopneumoniae and euthanized four weeks later to assess vaccine efficacy via macroscopic and microscopic evaluation of lung lesions. Blood and broncho-alveolar lavage fluid (BAL) samples were collected to measure antibody responses, cellular immunity, BAL cytokine levels and BAL M. hyopneumoniae DNA load as well as cytokine secretion by monocytes. Results: After vaccination, proliferation of antigen-specific CD3+ T cells and a higher percentage of TNF-α+ CD8+, and TNF-α+ and TNF-α+IFN-γ+ CD4+CD8+ T cells was seen in V1, while proliferation of or a significant increase in cytokine production by different T cell subsets could not be observed for animals from V2. Interestingly, LPS-stimulated blood monocytes from V1 and A secreted less IL-10 on D7. After challenge, higher levels of IgA, more IL-10 and less IL-1ß was detected in BAL from V1, which was not observed in V2. Animals from A had significantly more IL-17A in BAL. The macroscopic lung lesion score and the M. hyopneumoniae DNA load at euthanasia was lower in V1, but the microscopic lung lesion score was lower in both vaccinated groups. Discussion: In conclusion, these results indicate that the two commercial bacterins induced different local and adaptive immune responses, that the adjuvant alone can reduce anti-inflammatory innate immune responses, and that both vaccines had a different efficacy to reduce Mycoplasma-like lung lesions and M. hyopneumoniae DNA load in the lung.


Assuntos
Mycoplasma hyopneumoniae , Pneumonia Suína Micoplasmática , Suínos , Animais , Interleucina-10 , Fator de Necrose Tumoral alfa , Linfócitos T CD8-Positivos , Vacinas Bacterianas , Adjuvantes Imunológicos/farmacologia , Citocinas , Imunidade Celular
12.
Front Immunol ; 13: 992062, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36569949

RESUMO

As the global COVID-19 pandemic continues and new SARS-CoV-2 variants of concern emerge, vaccines remain an important tool for preventing the pandemic. The inactivated or subunit vaccines themselves generally exhibit low immunogenicity, which needs adjuvants to improve the immune response. We previously developed a receptor binding domain (RBD)-targeted and self-assembled nanoparticle to elicit a potent immune response in both mice and rhesus macaques. Herein, we further improved the RBD production in the eukaryote system by in situ Crispr/Cas9-engineered CHO cells. By comparing the immune effects of various Toll-like receptor-targeted adjuvants to enhance nanoparticle vaccine immunization, we found that Pam2CSK4, a TLR2/6 agonist, could mostly increase the titers of antigen-specific neutralizing antibodies and durability in humoral immunity. Remarkably, together with Pam2CSK4, the RBD-based nanoparticle vaccine induced a significant Th1-biased immune response and enhanced the differentiation of both memory T cells and follicular helper T cells. We further found that Pam2CSK4 upregulated migration genes and many genes involved in the activation and proliferation of leukocytes. Our data indicate that Pam2CSK4 targeting TLR2, which has been shown to be effective in tuberculosis vaccines, is the optimal adjuvant for the SARS-CoV-2 nanoparticle vaccine, paving the way for an immediate clinical trial.


Assuntos
Vacinas contra COVID-19 , COVID-19 , Animais , Humanos , Camundongos , Cricetinae , Receptor 2 Toll-Like/genética , Cricetulus , Macaca mulatta , Pandemias , SARS-CoV-2 , COVID-19/prevenção & controle , Adjuvantes Imunológicos/farmacologia , Adjuvantes Farmacêuticos , Imunidade Celular
13.
Front Immunol ; 13: 1051008, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36518761

RESUMO

Lumpy skin disease virus (LSDV) causes severe disease in cattle and water buffalo and is transmitted by hematophagous arthropod vectors. Detailed information of the adaptive and innate immune response to LSDV is limited, hampering the development of tools to control the disease. This study provides an in-depth analysis of the immune responses of calves experimentally inoculated with LSDV via either needle-inoculation or arthropod-inoculation using virus-positive Stomoxys calcitrans and Aedes aegypti vectors. Seven out of seventeen needle-inoculated calves (41%) developed clinical disease characterised by multifocal necrotic cutaneous nodules. In comparison 8/10 (80%) of the arthropod-inoculated calves developed clinical disease. A variable LSDV-specific IFN-γ immune response was detected in the needle-inoculated calves from 5 days post inoculation (dpi) onwards, with no difference between clinical calves (developed cutaneous lesions) and nonclinical calves (did not develop cutaneous lesions). In contrast a robust and uniform cell-mediated immune response was detected in all eight clinical arthropod-inoculated calves, with little response detected in the two nonclinical arthropod-inoculated calves. Neutralising antibodies against LSDV were detected in all inoculated cattle from 5-7 dpi. Comparison of the production of anti-LSDV IgM and IgG antibodies revealed no difference between clinical and nonclinical needle-inoculated calves, however a strong IgM response was evident in the nonclinical arthropod-inoculated calves but absent in the clinical arthropod-inoculated calves. This suggests that early IgM production is a correlate of protection in LSD. This study presents the first evidence of differences in the immune response between clinical and nonclinical cattle and highlights the importance of using a relevant transmission model when studying LSD.


Assuntos
Doença Nodular Cutânea , Vírus da Doença Nodular Cutânea , Bovinos , Animais , Vírus da Doença Nodular Cutânea/fisiologia , Doença Nodular Cutânea/prevenção & controle , Mosquitos Vetores , Imunidade Celular , Búfalos , Imunoglobulina M
14.
Front Immunol ; 13: 1016304, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36505442

RESUMO

The general immune state plays important roles against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Cells of the immune system are encountering rapid changes during the acute phase of SARS-CoV-2-induced disease. Reduced fraction of functional CD8+ T cells, disrupted cross-talking between CD8+ T cells with dendritic cells (DCs), and impaired immunological T-cell memory, along with the higher presence of hyperactive neutrophils, high expansion of myeloid-derived suppressor cells (MDSCs) and non-classical monocytes, and attenuated cytotoxic capacity of natural killer (NK) cells, are all indicative of low efficient immunity against viral surge within the body. Immune state and responses from pro- or anti-inflammatory cells of the immune system to SARS-CoV-2 are discussed in this review. We also suggest some strategies to enhance the power of immune system against SARS-CoV-2-induced disease.


Assuntos
COVID-19 , SARS-CoV-2 , Humanos , Linfócitos T CD8-Positivos , Imunidade Celular , Células Matadoras Naturais
15.
Front Immunol ; 13: 1049188, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36505469

RESUMO

Background: Immune responses to vaccines against severe acute respiratory syndrome (SARS)-coronavirus (CoV)-2 are variable. In the absence of disease, youngsters are expected to better react to vaccines than adults. Nevertheless, chronic immunosuppression in transplant recipients may impair their capability to generate protection. We aim to explore immune responses after BNT162b2 SARS-CoV-2 vaccination in our cohort of young liver-transplanted patients. Methods: A prospective study of adolescent liver-transplanted patients (n=33) in the long-term follow-up was performed. Immune responses after receiving Pfizer-BioNTech BNT162b2 vaccine were analyzed at two time-points: baseline and 30 days after the second dose. Humoral responses were measured by fluoroenzyme-immunoassay and T-cell responses by interferon-γ-release assay. Post-vaccine coronavirus disease (COVID-19) events were recorded by a survey. Results: Pre-vaccine SARS-CoV-2-specific antibodies were undetectable in 27/32 (84.4%), negative/indeterminate in 3/32 (9.4%) and positive in 2/32 (6.3%) patients. Cellular responses at baseline were negative in 12/18 (66.6%), positive in 3/18 (16.6%) and indeterminate in 3/18 (16.6%) recipients. None of the baseline positives recalled any symptoms. Post-vaccine antibodies were detected in all patients and 92.6% showed levels >816 BAU/mL. Twenty (71.4%) recipients had positive T-cell responses. Regarding post-vaccine SARS-Cov-2 infection, 10 (30.3%) patients reported COVID-19 without hospitalization and 21 (63.6%) did not notify any infection. Negative and positive cell-response groups after vaccination showed statistically significant differences regarding COVID-19 cases (62.5% vs 22.2%, respectively; p=0.046). Conclusions: Adolescents and young adults with liver transplantation responded to SARS-Cov-2 vaccine, generating both humoral and cellular responses. Recipients developing cellular responses after vaccination had a lower incidence of COVID-19.


Assuntos
COVID-19 , Transplante de Fígado , Vacinas , Adolescente , Adulto Jovem , Humanos , SARS-CoV-2 , Vacinas contra COVID-19 , Vacina BNT162 , Transplante de Fígado/efeitos adversos , Estudos Prospectivos , COVID-19/prevenção & controle , Anticorpos Antivirais , Imunidade Celular
16.
Sci Rep ; 12(1): 22330, 2022 12 25.
Artigo em Inglês | MEDLINE | ID: mdl-36567369

RESUMO

Elucidating the adaptive immune characteristics of natural protection to Lassa fever (LF) is vital in designing and selecting optimal vaccine candidates. With rejuvenated interest in LF and a call for accelerated research on the Lassa virus (LASV) vaccine, there is a need to define the correlates of natural protective immune responses to LF. Here, we describe cellular and antibody immune responses present in survivors of LF (N = 370) and their exposed contacts (N = 170) in a LASV endemic region in Nigeria. Interestingly, our data showed comparable T cell and binding antibody responses from both survivors and their contacts, while neutralizing antibody responses were primarily seen in the LF survivors and not their contacts. Neutralizing antibody responses were found to be cross-reactive against all five lineages of LASV with a strong bias to Lineage II, the prevalent strain in southern Nigeria. We demonstrated that both T cell and antibody responses were not detectable in peripheral blood after a decade in LF survivors. Notably LF survivors maintained high levels of detectable binding antibody response for six months while their contacts did not. Lastly, as potential vaccine targets, we identified the regions of the LASV Glycoprotein (GP) and Nucleoprotein (NP) that induced the broadest peptide-specific T cell responses. Taken together this data informs immunological readouts and potential benchmarks for clinical trials evaluating LASV vaccine candidates.


Assuntos
Febre Lassa , Vírus Lassa , Humanos , Nigéria/epidemiologia , Imunidade Celular , Anticorpos Neutralizantes , Sobreviventes
17.
Front Immunol ; 13: 1050211, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36532067

RESUMO

We evaluated the humoral and cellular immune responses and safety of the third severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) mRNA vaccine with a longer interval after the second vaccination in kidney transplant recipients (KTRs). We enrolled 54 kidney transplant recipients without a history of coronavirus disease 2019 (COVID-19), who received a third dose of the vaccine. We assessed anti-SARS-CoV-2 spike antibody and antigen-specific T cells using enzyme-linked immunospot (ELISpot) against the spike protein at baseline, after the second vaccination, and after the third vaccination. We also evaluated the adverse events related to each dose of the vaccine. The duration between the second and third vaccinations was 7 ± 1 month. All 17 (100%) KTRs with anti-SARS-CoV-2 antibody positivity after the second vaccination and 27 of 37 (73%) KTRs without anti-SARS-CoV-2 antibody positivity after the second vaccination were positive for anti-SARS-CoV-2 antibodies (p=0.022). Anti-SARS-CoV-2 antibody titers were significantly higher than those after the second vaccination (p<0.001). Age ≥ 60 years and lymphocyte count < 1150/mm3 were confirmed as risk factors for anti-SARS-CoV-2 antibody negativity after the third vaccination in multivariate regression analysis. ELISpot cytokine activities were positive after the third vaccination in 26 of 29 (90%) KTRs with ELISpot cytokine activity positivity after the second vaccination and 12 of 24 (50%) KTRs without ELISpot cytokine activity after the second vaccination. The rate of change in cytokine activity after the third vaccination was significantly higher than that after the second vaccination (p<0.001). Only lymphocyte counts less than 1150/mm3 were confirmed as risk factors for ELISpot cytokine activity negativity in the multivariate regression analysis. Systemic adverse events classified as greater than moderate did not differ for each vaccine dose. None of the patients showed clinical symptoms of acute rejection. The third SARS-CoV-2 mRNA vaccine administration, with a longer interval after the second vaccination, improved humoral and cellular immune responses to SARS-CoV-2 mRNA vaccines without severe adverse effects in the KTRs.


Assuntos
Vacinas contra COVID-19 , COVID-19 , Imunidade Celular , Imunidade Humoral , Transplante de Rim , Humanos , Pessoa de Meia-Idade , Anticorpos Antivirais/sangue , COVID-19/prevenção & controle , Vacinas contra COVID-19/imunologia , Citocinas , SARS-CoV-2 , Vacinação , Imunização Secundária
18.
Iran J Immunol ; 19(4): 414-426, 2022 12.
Artigo em Inglês | MEDLINE | ID: mdl-36585883

RESUMO

BACKGROUND: Niclosamide, a STAT3 inhibitor, is widely under investigation due to its anti-cancer properties. STAT3 also exhibits an exciting role in the immune responses. OBJECTIVE: This study aimed to evaluate the impact of niclosamide on immune response of mice. METHODS: Niclosamide was administered to balb/c mice. To evaluate cell-mediated immune response, a contact-hypersensitivity (CHS) test, cyclophosphamide-induced neutropenic assay, and carbon clearance test were performed, whereas a humoral immune response was evaluated by hemagglutination assay (HA) and mice lethality test. The concentration of TGF-ß1 was determined by enzyme-linked immunosorbent assay (ELISA) on murine peritoneal macrophages. RESULTS: In the CHS test, niclosamide caused a decrease in skin thickness, significantly exhibiting a decrease in inflammation. A highly significant decrease in overall leukocyte count (lymphocytes and neutrophils) was observed before and after cyclophosphamide injection as compared with the control group. However, only a highly significant decrease in the neutrophil percentage was observed. Niclosamide has decreased the phagocytic process immensely compared with the control. In the HA titer, niclosamide was found to reduce the antibodies' titer compared with the negative control group. In the mice lethality test, the treatment groups have shown an increase in the percentage of mortality. TGF-ß1 elevated in peritoneal macrophages when treated with niclosamide, in a dose-dependent manner. CONCLUSION: Niclosamide exerts potent immunomodulatory effects by significantly suppressing cell-mediated and humoral immune responses and increasing the levels of TGF-ß1 in mice. Niclosamide might be added as an adjuvant to immunosuppressive drugs for the treatment of autoimmune diseases.


Assuntos
Imunidade Humoral , Niclosamida , Camundongos , Animais , Niclosamida/farmacologia , Fator de Crescimento Transformador beta1 , Camundongos Endogâmicos BALB C , Imunidade Celular , Ciclofosfamida
19.
BMJ Case Rep ; 15(12)2022 Dec 13.
Artigo em Inglês | MEDLINE | ID: mdl-36524267

RESUMO

We present a female kidney transplant patient under conventional immunosuppression therapy. Her humoral immunity study (anti-spike-specific antibodies) was negative after the initial regimen and the third dose of vaccination against COVID-19. The specific ex vivo cellular immune study against spike of SARS-CoV-2 by interferon gamma release assay (IGRA) also remained at non-response levels at different time points despite an optimal non-specific cell immune response assessment. However, the cellular immunity test by delayed-type hypersensitivity (DTH) with spike of SARS-CoV-2 was always positive since the vaccination scheme began. Only after COVID-19 infection has there been a seroconversion of the patient's antibody tests along with IGRA positivity. The use of DTH test to measure the immune response could be a better and earlier parameter of the actual immune status that helps us to predict the immune response in real life. Hybrid immunity combining vaccine and natural infection could be a stronger stimulator of the specific global immune response.


Assuntos
COVID-19 , Transplante de Rim , Feminino , Humanos , SARS-CoV-2 , Pacientes , Vacinação , Imunidade Humoral , Anticorpos Antivirais , Imunidade Celular
20.
Front Immunol ; 13: 1031185, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36561750

RESUMO

Xenotransplantation has the potential to solve the shortfall of human organ donors. Genetically modified pigs have been considered as potential animal donors for human xenotransplantation and have been widely used in preclinical research. The genetic modifications aim to prevent the major species-specific barriers, which include humoral and cellular immune responses, and physiological incompatibilities such as complement and coagulation dysfunctions. Genetically modified pigs can be created by deleting several pig genes related to the synthesis of various pig specific antigens or by inserting human complement- and coagulation-regulatory transgenes. Finally, in order to reduce the risk of infection, genes related to porcine endogenous retroviruses can be knocked down. In this review, we focus on genetically modified pigs and comprehensively summarize the immunological mechanism of xenograft rejection and recent progress in preclinical and clinical studies. Overall, both genetically engineered pig-based xenografts and technological breakthroughs in the biomedical field provide a promising foundation for pig-to-human xenotransplantation in the future.


Assuntos
Animais Geneticamente Modificados , Engenharia Genética , Rejeição de Enxerto , Suínos , Animais , Humanos , Animais Geneticamente Modificados/genética , Proteínas do Sistema Complemento/genética , Xenoenxertos , Imunidade Celular , Suínos/genética , Transplante Heterólogo , Rejeição de Enxerto/prevenção & controle
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