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1.
J Headache Pain ; 25(1): 95, 2024 Jun 07.
Artigo em Inglês | MEDLINE | ID: mdl-38844851

RESUMO

BACKGROUND: The pathogenesis of migraine remains unclear; however, a large body of evidence supports the hypothesis that immunological mechanisms play a key role. Therefore, we aimed to review current studies on altered immunity in individuals with migraine during and outside attacks. METHODS: We searched the PubMed database to investigate immunological changes in patients with migraine. We then added other relevant articles on altered immunity in migraine to our search. RESULTS: Database screening identified 1,102 articles, of which 41 were selected. We added another 104 relevant articles. We found studies reporting elevated interictal levels of some proinflammatory cytokines, including IL-6 and TNF-α. Anti-inflammatory cytokines showed various findings, such as increased TGF-ß and decreased IL-10. Other changes in humoral immunity included increased levels of chemokines, adhesion molecules, and matrix metalloproteinases; activation of the complement system; and increased IgM and IgA. Changes in cellular immunity included an increase in T helper cells, decreased cytotoxic T cells, decreased regulatory T cells, and an increase in a subset of natural killer cells. A significant comorbidity of autoimmune and allergic diseases with migraine was observed. CONCLUSIONS: Our review summarizes the findings regarding altered humoral and cellular immunological findings in human migraine. We highlight the possible involvement of immunological mechanisms in the pathogenesis of migraine. However, further studies are needed to expand our knowledge of the exact role of immunological mechanisms in migraine pathogenesis.


Assuntos
Transtornos de Enxaqueca , Humanos , Transtornos de Enxaqueca/imunologia , Citocinas/imunologia , Imunidade Celular/imunologia , Imunidade Humoral/imunologia
2.
Nat Commun ; 15(1): 4913, 2024 Jun 08.
Artigo em Inglês | MEDLINE | ID: mdl-38851821

RESUMO

Host immune responses are tightly controlled by various immune factors during infection, and protozoan parasites also manipulate the immune system to evade surveillance, leading to an evolutionary arms race in host‒pathogen interactions; however, the underlying mechanisms are not fully understood. We observed that the level of superoxide dismutase 3 (SOD3) was significantly elevated in both Plasmodium falciparum malaria patients and mice infected with four parasite species. SOD3-deficient mice had a substantially longer survival time and lower parasitemia than control mice after infection, whereas SOD3-overexpressing mice were much more vulnerable to parasite infection. We revealed that SOD3, secreted from activated neutrophils, bound to T cells, suppressed the interleukin-2 expression and concomitant interferon-gamma responses crucial for parasite clearance. Overall, our findings expose active fronts in the arms race between the parasites and host immune system and provide insights into the roles of SOD3 in shaping host innate immune responses to parasite infection.


Assuntos
Malária Falciparum , Camundongos Endogâmicos C57BL , Camundongos Knockout , Neutrófilos , Superóxido Dismutase , Animais , Superóxido Dismutase/metabolismo , Superóxido Dismutase/genética , Humanos , Camundongos , Neutrófilos/imunologia , Malária Falciparum/imunologia , Malária Falciparum/parasitologia , Imunidade Celular , Linfócitos T/imunologia , Plasmodium falciparum/imunologia , Feminino , Interações Hospedeiro-Parasita/imunologia , Interações Hospedeiro-Parasita/genética , Interferon gama/metabolismo , Interferon gama/imunologia , Masculino , Imunidade Inata , Interleucina-2/metabolismo , Interleucina-2/imunologia , Interleucina-2/genética , Parasitemia/imunologia
3.
PLoS Negl Trop Dis ; 18(6): e0012229, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38857253

RESUMO

Leishmania donovani surface glycoprotein 63 (GP63) is a major virulence factor involved in parasite escape and immune evasion. In this study, we generated virus-like particles (VLPs) expressing L. donovani GP63 using the baculovirus expression system. Mice were intramuscularly immunized with GP63-VLPs and challenged with L. donovani promastigotes. GP63-VLP immunization elicited higher levels of L. donovani antigen-specific serum antibodies and enhanced splenic B cell, germinal center B cell, CD4+, and CD8+ T cell responses compared to unimmunized controls. GP63-VLPs inhibited the influx of pro-inflammatory cytokines IFN-γ and IL-6 in the livers, as well as thwarting the development of splenomegaly in immunized mice. Upon L. donovani challenge infection, a drastic reduction in splenic parasite burden was observed in VLP-immunized mice. These results indicate that GP63-VLPs immunization conferred protection against L. donovani challenge infection by inducing humoral and cellular immunity in mice.


Assuntos
Leishmania donovani , Leishmaniose Visceral , Camundongos Endogâmicos BALB C , Vacinas de Partículas Semelhantes a Vírus , Animais , Leishmania donovani/imunologia , Camundongos , Vacinas de Partículas Semelhantes a Vírus/imunologia , Vacinas de Partículas Semelhantes a Vírus/administração & dosagem , Feminino , Leishmaniose Visceral/prevenção & controle , Leishmaniose Visceral/imunologia , Anticorpos Antiprotozoários/sangue , Anticorpos Antiprotozoários/imunologia , Vacinas contra Leishmaniose/imunologia , Vacinas contra Leishmaniose/administração & dosagem , Eficácia de Vacinas , Imunidade Celular , Baço/imunologia , Linfócitos T CD8-Positivos/imunologia , Linfócitos B/imunologia , Imunidade Humoral , Glicoproteínas de Membrana/imunologia , Glicoproteínas de Membrana/genética , Citocinas/imunologia , Metaloendopeptidases
4.
Biochemistry (Mosc) ; 89(5): 872-882, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38880648

RESUMO

The pandemic of a new coronavirus infection that has lasted for more than 3 years, is still accompanied by frequent mutations in the S protein of SARS-CoV-2 and emergence of new virus variants causing new disease outbreak. Of all coronaviral proteins, the S and N proteins are the most immunogenic. The aim of this study was to compare the features of the humoral and T-cell immune responses to the SARS-CoV-2 S and N proteins in people with different histories of interaction with this virus. The study included 27 individuals who had COVID-19 once, 23 people who were vaccinated twice with the Sputnik V vaccine and did not have COVID-19, 22 people who had COVID-19 and were vaccinated twice with Sputnik V 6-12 months after the disease, and 25 people who had COVID-19 twice. The level of antibodies was determined by the enzyme immunoassay, and the cellular immunity was assessed by the expression of CD107a on CD8high lymphocytes after recognition of SARS-CoV-2 antigens. It was shown that the humoral immune response to the N protein was formed mainly by short-lived plasma cells synthesizing IgG antibodies of all four subclasses with a gradual switch from IgG3 to IgG1. The response to the S protein was formed by short-lived plasma cells at the beginning of the response (IgG1 and IgG3 subclasses) and then by long-lived plasma cells (IgG1 subclass). The dynamics of antibody level synthesized by the short-lived plasma cells was described by the Fisher equation, while changes in the level of antibodies synthesized by the long-lived plasma cells were described by the Erlang equation. The level of antibodies in the groups with the hybrid immunity exceeded that in the group with the post-vaccination immunity; the highest antibody content was observed in the group with the breakthrough immunity. The cellular immunity to the S and N proteins differed depending on the mode of immune response induction (vaccination or disease). Importantly, the response of heterologous CD8+ T cell to the N proteins of other coronaviruses may be involved in the immune defense against SARS-CoV-2.


Assuntos
Anticorpos Antivirais , COVID-19 , Proteínas do Nucleocapsídeo de Coronavírus , Imunidade Celular , Imunidade Humoral , SARS-CoV-2 , Glicoproteína da Espícula de Coronavírus , Humanos , SARS-CoV-2/imunologia , COVID-19/imunologia , COVID-19/virologia , Anticorpos Antivirais/imunologia , Anticorpos Antivirais/sangue , Masculino , Pessoa de Meia-Idade , Feminino , Adulto , Glicoproteína da Espícula de Coronavírus/imunologia , Proteínas do Nucleocapsídeo de Coronavírus/imunologia , Vacinas contra COVID-19/imunologia , Imunoglobulina G/sangue , Imunoglobulina G/imunologia , Fosfoproteínas/imunologia , Linfócitos T CD8-Positivos/imunologia , Idoso
5.
J Clin Immunol ; 44(6): 147, 2024 Jun 10.
Artigo em Inglês | MEDLINE | ID: mdl-38856804

RESUMO

PURPOSE: Asymptomatic SARS-CoV-2 infections were widely reported during the COVID-19 pandemic, acting as a hidden source of infection. Many existing studies investigating asymptomatic immunity failed to recruit true asymptomatic individuals. Thus, we conducted a longitudinal cohort study to evaluate humoral- and cell-mediated responses to infection and vaccination in well-defined asymptomatic young adults (the Asymptomatic COVID-19 in Education [ACE] cohort). METHODS: Asymptomatic testing services located at three UK universities identified asymptomatic young adults who were subsequently recruited with age- and sex-matched symptomatic and uninfected controls. Blood and saliva samples were collected after SARS-CoV-2 Wuhan infection, and again after vaccination. 51 participant's anti-spike antibody titres, neutralizing antibodies, and spike-specific T-cell responses were measured, against both Wuhan and Omicron B.1.1.529.1. RESULTS: Asymptomatic participants exhibited reduced Wuhan-specific neutralization antibodies pre- and post-vaccination, as well as fewer Omicron-specific neutralization antibodies post-vaccination, compared to symptomatic participants. Lower Wuhan and Omicron-specific IgG titres in asymptomatic individuals were also observed pre- and post-vaccination, compared to symptomatic participants. There were no differences in salivary IgA levels. Conventional flow cytometry analysis and multi-dimensional clustering analysis indicated unvaccinated asymptomatic participants had significantly fewer Wuhan-specific IL-2 secreting CD4+ CD45RA+ T cells and activated CD8+ T cells than symptomatic participants, though these differences dissipated after vaccination. CONCLUSIONS: Asymptomatic infection results in decreased antibody and T cell responses to further exposure to SARS-CoV-2 variants, compared to symptomatic infection. Post-vaccination, antibody responses are still inferior, but T cell immunity increases to match symptomatic subjects, emphasising the importance of vaccination to help protect asymptomatic individuals against future variants.


Assuntos
Anticorpos Neutralizantes , Anticorpos Antivirais , Infecções Assintomáticas , COVID-19 , Imunidade Celular , Imunidade Humoral , SARS-CoV-2 , Humanos , COVID-19/imunologia , SARS-CoV-2/imunologia , Masculino , Feminino , Anticorpos Antivirais/sangue , Anticorpos Neutralizantes/sangue , Anticorpos Neutralizantes/imunologia , Adulto Jovem , Adulto , Vacinas contra COVID-19/imunologia , Estudos de Coortes , Estudos Longitudinais , Vacinação , Imunoglobulina G/sangue , Imunoglobulina G/imunologia , Reino Unido/epidemiologia , Adolescente , Glicoproteína da Espícula de Coronavírus/imunologia
7.
Toxicology ; 505: 153836, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38768702

RESUMO

Caramel color is a widely used food pigment, and 2-Acetyl-4-tetrahydroxybutylimidazole (THI) is a by-products of Class III caramel color. Some studies have shown that THI can reduce the number of peripheral blood lymphocytes. However, the comprehensive mechanism of THI immunotoxicity requires further study. In this study, the effects of THI on lymphocyte count, humoral immunity, cellular immunity and nonspecific immunity were determined and the effect of the nutritional status of VB6 on THI immunotoxicity was evaluated. Female BALB/c mice were divided into 3 groups and fed chow containing different doses of VB6: VB6-normal (6 mg/kg VB6), VB6-deprived (0.5 mg/kg VB6) or VB6-enhanced (12 mg/kg VB6) feed. Each group was further divided into 4 subgroups and treated with THI (0.5, 2.5 or 12.5 mg/kg bw) or the solvent control by gavage for 30 days. The thymic cortical thickness was measured with ViewPoint; the proportions of major immune cells and T cells in peripheral blood and tissues were detected via flow cytometry; the transformation and proliferation abilities of T and B cells were detected via T and B lymphocyte proliferation assays; NK cell activity was assessed via lactate dehydrogenase assays; humoral immune function was assessed via plaque-forming cell assays; and the immune function of T lymphocytes was assessed via delayed type hypersensitivity assays. The results showed that compared with those in the corresponding control group, the white blood cell count and lymphocyte count decreased significantly in all the VB6-deprived groups, in the 2.5 and 12.5 mg/kg VB6 groups, and in the 12.5 mg/kg VB6-enhanced group. With increasing THI dose, the thymic cortical layer became thinner. In the thymus, THI increased the proportions of CD3+ T cells and mature CD8+ T cells and decreased the proportions of immature double-positive, double-negative T cells and CD69-expressing lymphocytes. The proportions of naïve T cells and Tcm (central memory T) cells related to homing decreased. The proportion of mature T cells in the spleen decreased significantly. The proliferation of T cells stimulated by ConA decreased after THI exposure. VB6-deficient mice were more sensitive to THI immunotoxicity, and supplementation with VB6 had a certain protective effect on these mice. The results of the PFC and NK cell activity assays indicated that THI exposure might not affect humoral immune or innate immune function.


Assuntos
Imidazóis , Imunidade Humoral , Camundongos Endogâmicos BALB C , Vitamina B 6 , Animais , Feminino , Camundongos , Imidazóis/toxicidade , Imidazóis/farmacologia , Imunidade Humoral/efeitos dos fármacos , Vitamina B 6/farmacologia , Vitamina B 6/administração & dosagem , Contagem de Linfócitos , Estado Nutricional/efeitos dos fármacos , Timo/efeitos dos fármacos , Timo/imunologia , Imunidade Celular/efeitos dos fármacos , Baço/efeitos dos fármacos , Baço/imunologia , Corantes de Alimentos/toxicidade , Proliferação de Células/efeitos dos fármacos , Linfócitos/efeitos dos fármacos , Linfócitos/imunologia , Linfócitos T/efeitos dos fármacos , Linfócitos T/imunologia
8.
Vaccine ; 42(17): 3733-3743, 2024 Jun 20.
Artigo em Inglês | MEDLINE | ID: mdl-38705805

RESUMO

Hand, foot, and mouth disease (HFMD) poses a significant public health threat primarily caused by four major enteroviruses: enterovirus 71 (EV71), coxsackieviruses A16, A10, and A6. Broadly protective immune responses are essential for complete protection against these major enteroviruses. In this study, we designed a new tetravalent immunogen for HFMD, validated it in silico, in vivo evaluated the immunogenicity of the DNA-based tetravalent vaccine in mice, and identified immunogenic B-cell and T-cell epitopes. A new tetravalent immunogen, VP1me, was designed based on the chimeric protein and epitope-based vaccine principles. It contains a complete EV71 VP1 protein and six reported neutralizing B-cell epitopes derived from the four major enteroviruses causing HFMD. In silico validation using multiple immunoinformatic tools indicated good attributes of the VP1me immunogen suitable for vaccine development. The VP1me-based DNA vaccine efficiently induced both humoral and cellular immune responses in BALB/cAJcl mice. A combination of in silico prediction and immunoassays enabled the identification of immunogenic linear B-cell and CD8 T-cell epitopes within the VP1me immunogen. Immunodominant linear B-cell epitopes were identified in six regions of VP1me, with one epitope located at the N-terminus of the VP1 protein (aa 9-23) regarded as a novel epitope. Interestingly, some B-cell epitopes could also induce the CD8 T-cell response, suggesting their dual functions in immune stimulation. These results lay the groundwork for further development of VP1me as a new vaccine candidate.


Assuntos
Anticorpos Antivirais , Epitopos de Linfócito B , Doença de Mão, Pé e Boca , Epitopos Imunodominantes , Camundongos Endogâmicos BALB C , Vacinas de DNA , Vacinas Virais , Animais , Vacinas de DNA/imunologia , Epitopos de Linfócito B/imunologia , Doença de Mão, Pé e Boca/prevenção & controle , Doença de Mão, Pé e Boca/imunologia , Camundongos , Vacinas Virais/imunologia , Epitopos Imunodominantes/imunologia , Anticorpos Antivirais/imunologia , Anticorpos Antivirais/sangue , Feminino , Epitopos de Linfócito T/imunologia , Proteínas do Capsídeo/imunologia , Proteínas do Capsídeo/genética , Enterovirus/imunologia , Anticorpos Neutralizantes/imunologia , Anticorpos Neutralizantes/sangue , Enterovirus Humano A/imunologia , Enterovirus Humano A/genética , Imunogenicidade da Vacina , Imunidade Celular , Imunidade Humoral
9.
PLoS One ; 19(5): e0303244, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38728294

RESUMO

To predict protective immunity to SARS-CoV-2, cellular immunity seems to be more sensitive than humoral immunity. Through an Interferon-Gamma (IFN-γ) Release Assay (IGRA), we show that, despite a marked decrease in total antibodies, 94.3% of 123 healthcare workers have a positive cellular response 6 months after inoculation with the 2nd dose of BNT162b2 vaccine. Despite the qualitative relationship found, we did not observe a quantitative correlation between IFN-γ and IgG levels against SARS-CoV-2. Using stimulated whole blood from a subset of participants, we confirmed the specific T-cell response to SARS-CoV-2 by dosing elevated levels of the IL-6, IL-10 and TNF-α. Through a 20-month follow-up, we found that none of the infected participants had severe COVID-19 and that the first positive cases were only 12 months after the 2nd dose inoculation. Future studies are needed to understand if IGRA-SARS-CoV-2 can be a powerful diagnostic tool to predict future COVID-19 severe disease, guiding vaccination policies.


Assuntos
Vacina BNT162 , COVID-19 , Pessoal de Saúde , Testes de Liberação de Interferon-gama , SARS-CoV-2 , Adulto , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Anticorpos Antivirais/sangue , Anticorpos Antivirais/imunologia , Vacina BNT162/imunologia , COVID-19/imunologia , COVID-19/prevenção & controle , Vacinas contra COVID-19/imunologia , Vacinas contra COVID-19/administração & dosagem , Imunidade Celular , Imunoglobulina G/sangue , Imunoglobulina G/imunologia , Interferon gama/sangue , Interleucina-10/sangue , Interleucina-10/imunologia , Interleucina-6/sangue , Interleucina-6/imunologia , SARS-CoV-2/imunologia , Fator de Necrose Tumoral alfa/sangue , Vacinação
10.
Int Immunopharmacol ; 134: 112160, 2024 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-38710117

RESUMO

INTRODUCTION: Cholera is a severe gastrointestinal disease that manifests with rapid onset of diarrhea, vomiting, and high mortality rates. Due to its widespread occurrence in impoverished communities with poor water sanitation, there is an urgent demand for a cost-effective and highly efficient vaccine. Multi-epitope vaccines containing dominant immunological epitopes and adjuvant compounds have demonstrated potential in boosting the immune response. MATERIAL AND METHODS: B and T epitopes of OMPU, OMPW, TCPA, CTXA, and CTXB proteins were predicted using bioinformatics methods. Subsequently, highly antigenic multi-epitopes that are non-allergenic and non-toxic were synthesized. These multi-epitopes were then cloned into the pCOMB phagemid. A plasmid M13KO7ΔpIII containing all helper phage proteins except pIII was created to produce the recombinant phage. Female Balb/c mice were divided into three groups and immunized accordingly. The mice received the helper phage, recombinant phage or PBS via gavage feeding thrice within two weeks. Serum samples were collected before and after immunization for the ELISA test as well as evaluating immune system induction through ELISpot testing of spleen lymphocytes. RESULTS: The titer of the recombinant phage was determined to be 1011 PFU/ml. The presence of the recombinant phage was confirmed through differences in optical density between sample and control groups in the ELISA phage technique, as well as by observing transduction activity, which demonstrated successful production of a recombinant phage displaying the Vibrio multi-epitope on M13 phage pIII. ELISA results revealed significant differences in phage antibodies before and after inoculation, particularly notable in the negative control mice. Mice treated with multi-epitope phages exhibited antibodies against Vibrio cholerae lysate. Additionally, ELISpot results indicated activation of cellular immunity in mice receiving both Vibrio and helper phage. CONCLUSION: This study emphasizes the potential of multi-epitope on phage to enhance both cellular and humoral immunity in mice, demonstrating how phages can be used as adjuvants to stimulate mucosal immunity and act as promising candidates for oral vaccination.


Assuntos
Anticorpos Antibacterianos , Vacinas contra Cólera , Cólera , Imunidade Celular , Imunidade Humoral , Camundongos Endogâmicos BALB C , Vibrio cholerae , Animais , Vibrio cholerae/imunologia , Feminino , Cólera/prevenção & controle , Cólera/imunologia , Vacinas contra Cólera/imunologia , Vacinas contra Cólera/administração & dosagem , Administração Oral , Camundongos , Anticorpos Antibacterianos/sangue , Epitopos de Linfócito T/imunologia , Epitopos de Linfócito T/genética , Imunização , Epitopos de Linfócito B/imunologia , Epitopos de Linfócito B/genética , Humanos , Bacteriófagos/imunologia , Antígenos de Bactérias/imunologia , Antígenos de Bactérias/genética
11.
J Control Release ; 370: 691-706, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38723671

RESUMO

Vaccination is essential for preventing and controlling infectious diseases, along with reducing mortality. Developing safe and versatile adjuvants to enhance humoral and cellular immune responses to vaccines remains a key challenge in vaccine development. Here, we designed hierarchical mesoporous MOF-801 (HM801) using a Cocamidopropyl betaine (CAPB) and a Pluronics F127 in an aqueous phase system. Meanwhile, we synthesized a novel SARS-CoV-2 nanovaccine (R@M@HM801) with a high loading capacity for both the STING agonist (MSA-2) and the Delta receptor binding domain (Delta-RBD) antigen. R@M@HM801 enhanced MSA-2 and RBD utilization and effectively co-delivered MSA-2 and RBD antigens to antigen-presenting cells in the draining lymph nodes, thereby promoting the activation of both T and B cells. Lymphocyte single-cell analysis showed that R@M@HM801 stimulated robust CD11b+CD4+ T cells, CXCR5+CD4+ T follicular helper (Tfh), and durable CD4+CD44+CD62L-, CD8+CD44+CD62L- effector memory T cell (TEM) immune responses, and promoted the proliferative activation of CD26+ B cells in vivo. Meanwhile, R@M@HM801 induced stronger specific antibodies and neutralization of pseudovirus against Delta compared to the RBD + MAS-2 and RBD + MAS-2 + Alum vaccines. Our study demonstrated the efficacy of a hierarchical mesoporous HM801 and its potential immune activation mechanism in enhancing adaptive immune responses against viruses and other diseases.


Assuntos
Adjuvantes Imunológicos , Imunidade Celular , Imunidade Humoral , Proteínas de Membrana , Estruturas Metalorgânicas , Animais , Imunidade Humoral/efeitos dos fármacos , Adjuvantes Imunológicos/farmacologia , Adjuvantes Imunológicos/administração & dosagem , Adjuvantes Imunológicos/química , Imunidade Celular/efeitos dos fármacos , Proteínas de Membrana/imunologia , Camundongos , Estruturas Metalorgânicas/química , Feminino , Vacinas contra COVID-19/imunologia , Vacinas contra COVID-19/administração & dosagem , SARS-CoV-2/imunologia , SARS-CoV-2/efeitos dos fármacos , Camundongos Endogâmicos BALB C , Porosidade , Camundongos Endogâmicos C57BL , Linfócitos B/imunologia , Linfócitos B/efeitos dos fármacos
12.
Antiviral Res ; 227: 105917, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38782067

RESUMO

The Fc-fused receptor binding domain (RBD-Fc) vaccine for SARS-CoV-2 has garnered significant attention for its capacity to provide effective and specific immune protection. However, its immunogenicity is limited, highlighting the need for improvement in clinical application. Nanoparticle delivery has been shown to be an effective method for enhancing antigen immunogenicity. In this study, we developed bivalent nanoparticle recombinant protein vaccines by assembling the RBD-Fc of SARS-CoV-2 and Fc-binding homo-oligomers o42.1 and i52.3 into octahedral and icosahedral nanoparticles. The formation of RBD-Fc nanoparticles was confirmed through structural characterization and cell binding experiments. Compared to RBD-Fc dimers, the nanoparticle vaccines induced more potent neutralizing antibodies (nAb) and stronger cellular immune responses. Therefore, using bivalent nanoparticle vaccines based on RBD-Fc presents a promising vaccination strategy against SARS-CoV-2 and offers a universal approach for enhancing the immunogenicity of Fc fusion protein vaccines.


Assuntos
Anticorpos Neutralizantes , Anticorpos Antivirais , Vacinas contra COVID-19 , COVID-19 , Fragmentos Fc das Imunoglobulinas , Nanopartículas , SARS-CoV-2 , Glicoproteína da Espícula de Coronavírus , Nanopartículas/química , SARS-CoV-2/imunologia , Vacinas contra COVID-19/imunologia , Anticorpos Neutralizantes/imunologia , Anticorpos Antivirais/imunologia , Humanos , Fragmentos Fc das Imunoglobulinas/imunologia , Fragmentos Fc das Imunoglobulinas/química , COVID-19/prevenção & controle , COVID-19/imunologia , Glicoproteína da Espícula de Coronavírus/imunologia , Glicoproteína da Espícula de Coronavírus/química , Animais , Camundongos , Vacinas Sintéticas/imunologia , Vacinas Sintéticas/administração & dosagem , Vacinas Sintéticas/química , Proteínas Recombinantes de Fusão/imunologia , Proteínas Recombinantes de Fusão/genética , Proteínas Recombinantes de Fusão/química , Feminino , Multimerização Proteica , Camundongos Endogâmicos BALB C , Desenvolvimento de Vacinas , Ligação Proteica , Imunogenicidade da Vacina , Imunidade Celular , Nanovacinas
13.
Dev Comp Immunol ; 158: 105198, 2024 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-38795942

RESUMO

Immune-priming occurs in insects after a prior pathogen exposure. However, its underlying mechanism in insects remains elusive. In the present work, immune-priming was detected in a lepidopteran insect, Spodoptera exigua. Specifically, a prior infection with a heat-killed pathogenic bacterium, Escherichia coli, led to increased survival upon the second infection of different pathogens. Plasma collected from larvae with the prior infection possessed the immune-priming factor(s) that significantly up-regulated cellular and humoral immune responses of naïve larvae. Our study also finds that variations in the timing of plasma collection for priming larvae resulted in distinct impacts on both cellular and humoral responses. However, when the active plasma exhibiting the immune-priming was heat-treated, it lost this priming activity, therefore suggesting that protein factor(s) play a role in this immune-priming. An immunofluorescence assay showed that the hemocytes collected from the immune-primed larvae highly reacted to a polyclonal antibody specific to a vertebrate lipocalin, apolipoprotein D (ApoD). Among 27 ApoD genes (Se-ApoD1 âˆ¼ Se-ApoD27) of S. exigua, Se-ApoD3 was found to be highly induced during the immune-priming, in which it was shown to be expressed in hemocytes and fat body from a fluorescence in situ hybridization analysis. RNA interference of Se-ApoD3 expression significantly impaired the immune-priming of S. exigua larvae. Moreover, the inhibition of eicosanoid biosynthesis suppressed the immune-priming, in which treatment with a lipoxygenase (LOX) inhibitor-and not treatment with a cyclooxygenase inhibitor-suppressed immune-priming. Further, an addition of LOX product such as lipoxin A4 or lipoxin B4 significantly rescued the lost immune-priming activity. Taken together, these results suggest that a complex of ApoD3 and LOX product mediates the immune-priming activity of S. exigua.


Assuntos
Apolipoproteínas , Escherichia coli , Hemócitos , Proteínas de Insetos , Larva , Spodoptera , Animais , Spodoptera/imunologia , Proteínas de Insetos/metabolismo , Proteínas de Insetos/genética , Proteínas de Insetos/imunologia , Escherichia coli/imunologia , Larva/imunologia , Hemócitos/imunologia , Hemócitos/metabolismo , Apolipoproteínas/metabolismo , Apolipoproteínas/imunologia , Apolipoproteínas/genética , Imunidade Humoral , Lipoxigenase/metabolismo , Lipoxigenase/genética , Lipoxigenase/imunologia , Imunidade Celular
14.
Transpl Infect Dis ; 26(3): e14290, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38708941

RESUMO

BACKGROUND: Cytomegalovirus-specific T-cell-mediated immunity (CMV-CMI) protects from CMV infection in allogeneic hematopoietic cell transplantation (allo-HCT), but to date, there is no validated measure of CMV immunity for this population. METHODS: In this prospective, observational, pilot study, CMV T-cell responses were evaluated monthly and at onset of graft-versus-host disease (GVHD) or CMV infection in CMV-seropositive allo-HCT recipients using a commercial flow cytometry assay, the CMV inSIGHT T-Cell Immunity Panel (CMV-TCIP). The primary endpoint was the time to first positive CMV-TCIP, defined as percentage of interferon-γ-producing CD4+ or CD8+ CMV-specific T cells >0.2%. Letermovir was prescribed from day +10 to ≥100. RESULTS: Twenty-eight allo-HCT recipients were enrolled. The median time to first positive CMV-TCIP result was earlier for CD4+ (60 days [interquartile range, IQR 33‒148]) than for CD8+ T cells (96 days [IQR 33‒155]) and longer for haploidentical and mismatched transplant recipients (77 and 96 days, respectively) than for matched donors (45 and 33 days, respectively). CD4+ and CD8+ CMV-CMI recovery was sustained in 10/10 (100%) and 10/11 (91%) patients, respectively, without GVHD, whereas CD4+ and/or CD8+ CMV-CMI was lost in 4/6 and 2/6 patients, respectively, with GVHD requiring steroids. As a predictor of clinically significant CMV infection in patients with low-level CMV reactivation, the sensitivity and negative predictive value of CMV-TCIP were 90% and 87.5%, respectively, for CD4+ CMV-TCIP and 66.7% and 62.5%, respectively, for CD8+ CMV-TCIP. CONCLUSIONS: There was significant variability in time to CMV-CMI recovery post-HCT, with slower recovery after haploidentical and mismatched HCT. CD4+ CMV-CMI may protect against CS-CMVi, but immunity may be lost with GVHD diagnosis and treatment.


Assuntos
Linfócitos T CD4-Positivos , Linfócitos T CD8-Positivos , Infecções por Citomegalovirus , Citomegalovirus , Citometria de Fluxo , Doença Enxerto-Hospedeiro , Transplante de Células-Tronco Hematopoéticas , Transplante Homólogo , Humanos , Projetos Piloto , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Infecções por Citomegalovirus/imunologia , Infecções por Citomegalovirus/virologia , Infecções por Citomegalovirus/prevenção & controle , Pessoa de Meia-Idade , Masculino , Citomegalovirus/imunologia , Estudos Prospectivos , Feminino , Citometria de Fluxo/métodos , Adulto , Doença Enxerto-Hospedeiro/imunologia , Doença Enxerto-Hospedeiro/prevenção & controle , Linfócitos T CD8-Positivos/imunologia , Linfócitos T CD4-Positivos/imunologia , Transplante Homólogo/efeitos adversos , Idoso , Imunidade Celular , Antivirais/uso terapêutico
15.
Antiviral Res ; 227: 105914, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38759930

RESUMO

Due to the severity of CMV infection in immunocompromised individuals the development of a vaccine has been declared a priority. However, despite the efforts made there is no yet a vaccine available for clinical use. We designed an approach to identify new CMV antigens able to inducing a broad immune response that could be used in future vaccine formulations. We have used serum samples from 28 kidney transplant recipients, with a previously acquired CMV-specific immune response to identify viral proteins that were recognized by the antibodies present in the patient serum samples by Western blot. A band of approximately 45 kDa, identified as UL44, was detected by most serum samples. UL44 immunogenicity was tested in BALB/c mice that received three doses of the UL44-pcDNA DNA vaccine. UL44 elicited both, a strong antibody response and CMV-specific cellular response. Using bioinformatic analysis we demonstrated that UL44 is a highly conserved protein and contains epitopes that are able to activate CD8 lymphocytes of the most common HLA alleles in the world population. We constructed a UL44 ORF deletion mutant virus that produced no viral progeny, suggesting that UL44 is an essential viral protein. In addition, other authors have demonstrated that UL44 is one of the most abundant viral proteins after infection and have suggested an essential role of UL44 in viral replication. Altogether, our data suggests that UL44 is a potent antigen, and favored by its abundance, it may be a good candidate to include in a vaccine formulation.


Assuntos
Infecções por Citomegalovirus , Citomegalovirus , Camundongos Endogâmicos BALB C , Proteínas Virais , Animais , Camundongos , Humanos , Citomegalovirus/imunologia , Citomegalovirus/genética , Infecções por Citomegalovirus/imunologia , Infecções por Citomegalovirus/virologia , Proteínas Virais/imunologia , Proteínas Virais/genética , Anticorpos Antivirais/sangue , Anticorpos Antivirais/imunologia , Vacinas de DNA/imunologia , Vacinas de DNA/administração & dosagem , Feminino , Vacinas contra Citomegalovirus/imunologia , Vacinas contra Citomegalovirus/administração & dosagem , Linfócitos T/imunologia , Antígenos Virais/imunologia , Transplante de Rim , Linfócitos T CD8-Positivos/imunologia , Imunidade Celular
17.
EBioMedicine ; 104: 105153, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38805853

RESUMO

BACKGROUND: The development of a universal influenza virus vaccine, to protect against both seasonal and pandemic influenza A viruses, is a long-standing public health goal. The conserved stalk domain of haemagglutinin (HA) is a promising vaccine target. However, the stalk is immunosubdominant. As such, innovative approaches are required to elicit robust immunity against this domain. In a previously reported observer-blind, randomised placebo-controlled phase I trial (NCT03300050), immunisation regimens using chimeric HA (cHA)-based immunogens formulated as inactivated influenza vaccines (IIV) -/+ AS03 adjuvant, or live attenuated influenza vaccines (LAIV), elicited durable HA stalk-specific antibodies with broad reactivity. In this study, we sought to determine if these vaccines could also boost T cell responses against HA stalk, and nucleoprotein (NP). METHODS: We measured interferon-γ (IFN-γ) responses by Enzyme-Linked ImmunoSpot (ELISpot) assay at baseline, seven days post-prime, pre-boost and seven days post-boost following heterologous prime:boost regimens of LAIV and/or adjuvanted/unadjuvanted IIV-cHA vaccines. FINDINGS: Our findings demonstrate that immunisation with adjuvanted cHA-based IIVs boost HA stalk-specific and NP-specific T cell responses in humans. To date, it has been unclear if HA stalk-specific T cells can be boosted in humans by HA-stalk focused universal vaccines. Therefore, our study will provide valuable insights for the design of future studies to determine the precise role of HA stalk-specific T cells in broad protection. INTERPRETATION: Considering that cHA-based vaccines also elicit stalk-specific antibodies, these data support the further clinical advancement of cHA-based universal influenza vaccine candidates. FUNDING: This study was funded in part by the Bill and Melinda Gates Foundation (BMGF).


Assuntos
Anticorpos Antivirais , Glicoproteínas de Hemaglutininação de Vírus da Influenza , Imunidade Celular , Vacinas contra Influenza , Influenza Humana , Humanos , Vacinas contra Influenza/imunologia , Vacinas contra Influenza/administração & dosagem , Glicoproteínas de Hemaglutininação de Vírus da Influenza/imunologia , Influenza Humana/prevenção & controle , Influenza Humana/imunologia , Anticorpos Antivirais/imunologia , Feminino , Adulto , Masculino , Linfócitos T/imunologia , Imunização Secundária , Interferon gama/metabolismo , Nucleoproteínas/imunologia , Adulto Jovem , Vírus da Influenza A/imunologia
18.
Yakugaku Zasshi ; 144(5): 475-481, 2024.
Artigo em Japonês | MEDLINE | ID: mdl-38692920

RESUMO

Zinc is one of the essential trace elements, and is involved in various functions in the body. Zinc deficiency is known to cause immune abnormalities, but the mechanism is not fully understood. Therefore, we focused our research on tumor immunity to elucidate the effect of zinc on colorectal cancer and its mechanisms. Mice were treated with azoxymethane (AOM) and dextran sodium sulfate (DSS) to develop colorectal cancer, then the relationship between zinc content in the diet and the number and area of tumors in the colon was observed. The number of tumors in the colon was significantly higher in the no-zinc-added diet group compared to the normal zinc intake group, and about half the number in the high-zinc-intake group compared to the normal-zinc-intake group. In T-cell-deficient mice, the number of tumors in the high-zinc-intake group was similar to that in the normal-zinc-intake group, suggesting that the inhibitory effect of zinc was dependent on T cells. Furthermore, we found that the amount of granzyme B transcript released by cytotoxic T cells upon antigen stimulation was significantly increased by the addition of zinc. We also showed that granzyme B transcriptional activation by zinc addition was dependent on calcineurin activity. Collectively, we have shown that zinc exerts its tumor-suppressive effect by acting on cytotoxic T cells, the center of cellular immunity, and that it increases the transcription of granzyme B, one of the key molecules involved in tumor immunity. In this symposium, we would like to introduce our latest data on the relationship between zinc and tumor immunity.


Assuntos
Neoplasias Colorretais , Imunidade Celular , Zinco , Animais , Humanos , Camundongos , Azoximetano , Neoplasias Colorretais/imunologia , Neoplasias Colorretais/etiologia , Neoplasias Colorretais/prevenção & controle , Modelos Animais de Doenças , Granzimas/metabolismo , Linfócitos T Citotóxicos/imunologia
19.
Int Immunopharmacol ; 134: 112141, 2024 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-38733819

RESUMO

BACKGROUND: Novel coronaviruses constitute a significant health threat, prompting the adoption of vaccination as the primary preventive measure. However, current evaluations of immune response and vaccine efficacy are deemed inadequate. OBJECTIVES: The study sought to explore the evolving dynamics of immune response at various vaccination time points and during breakthrough infections. It aimed to elucidate the synergistic effects of epidemiological factors, humoral immunity, and cellular immunity. Additionally, regression curves were used to determine the correlation between the protective efficacy of the vaccine and the stimulated immune response. METHODS: Employing LASSO for high-dimensional data analysis, the study utilised four machine learning algorithms-logistical regression, random forest, LGBM classifier, and AdaBoost classifier-to comprehensively assess the immune response following booster vaccination. RESULTS: Neutralising antibody levels exhibited a rapid surge post-booster, escalating to 102.38 AU/mL at one week and peaking at 298.02 AU/mL at two weeks. Influential factors such as sex, age, disease history, and smoking status significantly impacted post-booster antibody levels. The study further constructed regression curves for neutralising antibodies, non-switched memory B cells, CD4+T cells, and CD8+T cells using LASSO combined with the random forest algorithm. CONCLUSION: The establishment of an artificial intelligence evaluation system emerges as pivotal for predicting breakthrough infection prognosis after the COVID-19 booster vaccination. This research underscores the intricate interplay between various components of immunity and external factors, elucidating key insights to enhance vaccine effectiveness. 3D modelling discerned distinctive interactions between humoral and cellular immunity within prognostic groups (Class 0-2). This underscores the critical role of the synergistic effect of humoral immunity, cellular immunity, and epidemiological factors in determining the protective efficacy of COVID-19 vaccines post-booster administration.


Assuntos
Anticorpos Antivirais , Inteligência Artificial , Vacinas contra COVID-19 , COVID-19 , SARS-CoV-2 , Vacinas de Produtos Inativados , Humanos , COVID-19/prevenção & controle , COVID-19/imunologia , Feminino , Vacinas contra COVID-19/imunologia , Masculino , SARS-CoV-2/imunologia , Pessoa de Meia-Idade , Adulto , Vacinas de Produtos Inativados/imunologia , Anticorpos Antivirais/sangue , Estudos Prospectivos , Imunidade Humoral , Anticorpos Neutralizantes/sangue , Eficácia de Vacinas , Imunização Secundária , Aprendizado de Máquina , Idoso , Adulto Jovem , Imunidade Celular
20.
Front Immunol ; 15: 1374486, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38745651

RESUMO

A universal recombinant adenovirus type-5 (Ad5) vaccine against COVID19 (Ad-US) was constructed, and immunogenicity and broad-spectrum of Ad5-US were evaluated with both intranasal and intramuscular immunization routes. The humoral immune response of Ad5-US in serum and bronchoalveolar lavage fluid were evaluated by the enzyme-linked immunosorbent assay (ELISA), recombinant vesicular stomatitis virus based pseudovirus neutralization assay, and angiotensin-converting enzyme-2 (ACE2) -binding inhibition assay. The cellular immune response and Th1/Th2 biased immune response of Ad5-US were evaluated by the IFN-γ ELISpot assay, intracellular cytokine staining, and Meso Scale Discovery (MSD) profiling of Th1/Th2 cytokines. Intramuscular priming followed by an intranasal booster with Ad5-US elicited the broad-spectrum and high levels of IgG, IgA, pseudovirus neutralizing antibody (PNAb), and Th1-skewing of the T-cell response. Overall, the adenovirus type-5 vectored universal SARS-CoV-2 vaccine Ad5-US was successfully constructed, and Ad5-US was highly immunogenic and broad spectrum. Intramuscular priming followed by an intranasal booster with Ad5-US induced the high and broad spectrum systemic immune responses and local mucosal immune responses.


Assuntos
Anticorpos Neutralizantes , Anticorpos Antivirais , Vacinas contra COVID-19 , COVID-19 , Vetores Genéticos , SARS-CoV-2 , Vacinas contra COVID-19/imunologia , Vacinas contra COVID-19/administração & dosagem , COVID-19/prevenção & controle , COVID-19/imunologia , SARS-CoV-2/imunologia , SARS-CoV-2/genética , Animais , Anticorpos Antivirais/sangue , Anticorpos Antivirais/imunologia , Anticorpos Neutralizantes/imunologia , Anticorpos Neutralizantes/sangue , Camundongos , Humanos , Feminino , Vacinas Sintéticas/imunologia , Vacinas Sintéticas/administração & dosagem , Adenoviridae/genética , Adenoviridae/imunologia , Camundongos Endogâmicos BALB C , Administração Intranasal , Injeções Intramusculares , Imunidade Humoral , Citocinas/metabolismo , Imunidade Celular
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