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1.
Inflamm Bowel Dis ; 2024 Oct 16.
Artigo em Inglês | MEDLINE | ID: mdl-39412147

RESUMO

BACKGROUND: Children with inflammatory bowel disease (IBD) may have diminished serologic response to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccination and increased risk for subsequent severe coronavirus disease 2019 (COVID-19) infection. We sought to describe outcomes among those who developed SARS-CoV-2 infection following vaccination, characterize SARS-CoV-2 antibodies 1 year post-vaccination, and identify factors associated with durable serologic response. METHODS: We recruited children with IBD who received ≥2 doses of SARS-CoV-2 vaccine and prospectively collected data on (1) demographics, IBD characteristics, and therapy and (2) SARS-CoV-2 vaccination, testing, and infection symptoms. Serum was obtained for measurement of anti-receptor-binding domain IgG antibodies following a 2-part immunization at 12 and 52 weeks. RESULTS: We enrolled 298 participants (mean age 11.9 ±â€…3.82, 50% female, 67% Crohn's disease). Symptomatic COVID-19 infection after vaccination occurred in half of the participants, although only 2 (1%) required hospitalization. Anti-tumor necrosis factor alpha (TNF-α) was associated with higher likelihood of symptomatic COVID-19 infection, with an adjusted hazard ratio of 2.7 (95% CI, 1.5-5.0; P = .001). Nearly all participants (99%) had detectable antibody at Week 52. Children aged 1-5 years had lower 52-week antibody level compared to older children (P = .04), as did those on anti-TNF-α therapy (P = .007) and those who received only 2 vaccine doses prior to Week 52 (P < .001). CONCLUSIONS: SARS-CoV-2 vaccination provides lasting serologic response and protection against severe COVID-19 for most children with IBD, despite the use of lower vaccine doses in younger children and wide-ranging classes of immunosuppressive therapies.


We demonstrate high rates of durable antibody response and low rates of coronavirus disease 2019-related hospitalization 1 year following severe acute respiratory syndrome coronavirus 2 vaccination in children with inflammatory bowel disease. Anti-tumor necrosis factor alpha therapy, young age, and fewer vaccine doses were associated with lower 52-week antibody level.

2.
Proc Natl Acad Sci U S A ; 121(42): e2413619121, 2024 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-39382992

RESUMO

Antibodies are an essential component of the antiviral response in many species, but to date, there is no compelling evidence that bats are capable of eliciting a robust humoral immunity, including neutralizing antibodies. Here, we report that infection of Jamaican fruit bats with the bat influenza A virus H18N11 elicits a rapid and stable humoral immune response with a strong neutralizing capacity, associated with no detectable viral shedding after repeat challenge infection. Thus, the neutralizing antibody response of bats might play an important role in the bat immunity.


Assuntos
Anticorpos Neutralizantes , Anticorpos Antivirais , Quirópteros , Infecções por Orthomyxoviridae , Quirópteros/virologia , Quirópteros/imunologia , Animais , Anticorpos Neutralizantes/imunologia , Infecções por Orthomyxoviridae/imunologia , Infecções por Orthomyxoviridae/virologia , Infecções por Orthomyxoviridae/veterinária , Anticorpos Antivirais/imunologia , Vírus da Influenza A/imunologia , Eliminação de Partículas Virais/imunologia
3.
J Virol Methods ; 331: 115044, 2024 Oct 14.
Artigo em Inglês | MEDLINE | ID: mdl-39413880

RESUMO

Rabies virus glycoprotein (RABV-G) is responsible for the recognition of specific cell surface receptors and induces the production of neutralizing antibodies (VNA). Since RABV-G is a glycoprotein, this work aimed to evaluate Lens culinaris (LCA) chromatography as a simple and effective purification method. The purity and identification of the protein obtained were analyzed by SDS-PAGE, ELISA and lectin-binding assay. The antigenic properties of the purified RABV-G were evaluated by direct ELISA using human serum samples from individuals who had received rabies pre-exposure vaccination. For the immunogenicity study, Swiss Webster mice were immunized with purified RABV-G and the specific antibodies were measured by direct ELISA and RFFIT. As results, it was observed that the purified protein reveled a molecular mass of 55 kDa and the presence of carbohydrate; additionally, it was recognized by anti-rabies virus glycoprotein monoclonal antibody. Purified RABV-G induced high VNA titers (>50.0 IU/ml) in vivo, as detected by RFFIT, as well as RABV-G specific IgG1 (0.8 mean OD±SD) and IgG2a (0.3 mean OD±SD) antibodies, with a predominance of IgG1 (p< 0.001). In addition, it was observed that RABV-G was efficient in selectively detecting anti- RABV-G IgG in the sera of vaccinated individuals compared to the negative control. Therefore, LCA chromatography was efficient in preserving the native properties of RABV-G that are essential in inducing an adequate humoral immune response. In addition, the purified RABV-G presented analytical potential as an ELISA reagent.

4.
J Thromb Haemost ; 2024 Oct 28.
Artigo em Inglês | MEDLINE | ID: mdl-39476969

RESUMO

BACKGROUND: The most significant treatment complication for patients with hemophilia A is the development of neutralizing immunoglobin G (IgG), termed inhibitors, against factor VIII (FVIII) which prevent FVIII replacement therapy. Low titers of FVIII-specific immunoglobin M (IgM) have been identified in hemophilia A patients with and without inhibitors, as well as healthy individuals. However, the duration and influence of IgM on the immune response to FVIII remains unclear. OBJECTIVE: To characterize the binding interactions of persistently secreted FVIII-specific IgM in hemophilia A mice and assess their effect on IgG antibody development. METHODS: Splenic-derived monoclonal antibodies (MAbs) from immunized FVIII knockout mice were isolated and purified using hybridoma technology. Binding interactions were assessed utilizing a novel fluid-phase ELISA and computational modeling with HADDOCK to account for weak IgM binding. RESULTS: Sixteen porcine cross-reactive and non-inhibitory FVIII-specific IgM MAbs were identified. RNA sequencing of FVIII-specific IgM revealed 13 unique VDJ/VJ sequences indicating derivation from 13 unique B cell clones. IgM demonstrated polyclonal and polyreactive binding to FVIII in vitro and in silico. Molecular docking studies with reconstructed IgM VDJ/VJ regions identified frequent IgM interactions with amino acid residues K376, T381, K437, R2215 or K2249 within the FVIII A2 and C2 domains. Injections of individual IgM prior to FVIII exposure and co-injection of FVIII/IgM immune complexes did not affect de novo FVIII antibody production. CONCLUSION: Persistent FVIII-specific IgM are polyclonal but preferentially bind the A2 and C2 domains and FVIII/IgM immune complex formation do not significantly alter inhibitor development.

5.
Hum Vaccin Immunother ; 20(1): 2406065, 2024 Dec 31.
Artigo em Inglês | MEDLINE | ID: mdl-39327639

RESUMO

Candida albicans Is a leading cause of nosocomial bloodstream infections, particularly in immunocompromised patients. Current therapeutic strategies are insufficient, highlighting the need for effective vaccines. This study aimed to evaluate the efficacy of a dual-antigen fusion protein vaccine (AH) targeting the Als3 and Hyr1 proteins of C. albicans, using AlPO4 as an adjuvant. The AH vaccine was constructed by fusing Als317-432 and Hyr125-350 proteins, and its immunogenicity was tested in BALB/c mice and New Zealand white rabbits. Mice received three intramuscular doses of the vaccine combined with AlPO4, followed by a lethal challenge with C. albicans SC5314. Survival rates, antibody responses, cytokine production, fungal burdens, and organ pathology were assessed. The vaccine's efficacy was also validated using rabbit serum. Mice vaccinated with the AH-AlPO4 combination exhibited significantly higher antibody titers, particularly IgG and its subclasses, compared to controls (p < .001). The survival rate of vaccinated mice was 80% post-infection, significantly higher than the control group (p < .01). Vaccinated mice showed reduced fungal loads in the blood, kidneys, spleen, and liver (p < .05). Increased levels of interferon gamma and interleukin (IL)-17A were observed, indicating robust T helper (Th) 1 and Th17 cell responses. Vaccination mitigated organ damage, with kidney and liver pathology scores significantly lower than those of unvaccinated mice (p < .05). Rabbit serum with polyclonal antibodies demonstrated effective antifungal activity, confirming vaccine efficacy across species. The AH-AlPO4 vaccine effectively induced strong immune responses, reduced fungal burden, and protected against organ pathology in C. albicans infections. These findings support further development of dual-antigen vaccine strategies.


Candida, a fungus, is a major cause of bloodstream infections, especially in critical care settings. This study focused on developing a vaccine to protect against Candida infection. The vaccine targeted two key proteins, Als3p and Hyr1p, found on the surface of Candida, using a combination of these proteins. To create the vaccine, we used Als3p and Hyr1p to form a fusion protein called AH, and tested the vaccine on mice, administering it with different adjuvants (substances that enhance the immune response). The results showed that the AH vaccine, particularly when combined with the adjuvant AlPO4, induced a strong immune response in mice. This response included the production of specific antibodies and immune cells that are crucial for defending against Candida infections. Furthermore, mice receiving the AH-AlPO4 vaccine showed significantly better survival rates and lower levels of fungal infection compared to the control group or another experimental group. The vaccine also protected vital organs, such as the kidneys and liver, from Candida-induced damage. Additionally, we used rabbit serum to validate the efficacy of the vaccine, providing cross-species confirmation of its effectiveness. The study demonstrated the potential of the AH vaccine in eliciting robust immune responses and reducing the severity of Candida albicans infections. In summary, this research introduces a promising AH vaccine, which shows effectiveness in protecting against Candida infections. The study's innovative approach and positive results contribute to the ongoing efforts to develop vaccines against fungal infections, addressing a critical healthcare challenge. Further research is needed to explore the vaccine's long-term effectiveness and safety for potential use in clinical settings.


Assuntos
Adjuvantes Imunológicos , Anticorpos Antifúngicos , Antígenos de Fungos , Candida albicans , Candidíase , Vacinas Fúngicas , Camundongos Endogâmicos BALB C , Proteínas Recombinantes de Fusão , Animais , Vacinas Fúngicas/imunologia , Vacinas Fúngicas/administração & dosagem , Candida albicans/imunologia , Candidíase/prevenção & controle , Candidíase/imunologia , Anticorpos Antifúngicos/sangue , Anticorpos Antifúngicos/imunologia , Coelhos , Proteínas Recombinantes de Fusão/imunologia , Proteínas Recombinantes de Fusão/genética , Camundongos , Feminino , Antígenos de Fungos/imunologia , Antígenos de Fungos/administração & dosagem , Adjuvantes Imunológicos/administração & dosagem , Proteínas Fúngicas/imunologia , Proteínas Fúngicas/administração & dosagem , Citocinas , Vacinação/métodos , Imunoglobulina G/sangue , Modelos Animais de Doenças , Interleucina-17/imunologia , Interferon gama/imunologia , Eficácia de Vacinas , Análise de Sobrevida , Compostos de Alúmen
6.
BMC Vet Res ; 20(1): 407, 2024 Sep 11.
Artigo em Inglês | MEDLINE | ID: mdl-39261948

RESUMO

BACKGROUND: Rabbit hemorrhagic disease (RHD) is an acute infectious disease that damages the rabbit industry by producing significant mortality rates in young and adult rabbits. RHD is better controlled by vaccination. OBJECTIVE: The current study's goal was to prepare and evaluate the immuno-enhancing effect of montanide ISA70 and aluminum hydroxide (Al(OH)3) gel incorporated within the inactivated RHDV2 vaccine and assess the vaccine's protective efficacy against the homologous and heterologous local RHDV2 strains in rabbits. METHODS: Inactivated RHDV vaccines were prepared using Montanide ISA70 oil or Al(OH)3 gel adjuvants and submitted to sterility, safety, and potency tests. 200 rabbits were equally divided into 4 groups: G1 (control), G2 (vaccinated with gel-incorporated vaccine), G3 (vaccinated with montanide-incorporated vaccine), and G4 (vaccinated with gel- and montanide-incorporated vaccines). Individual blood samples were collected from one week to six months from all groups. The vaccine's potency was measured by the HI test and protection percentage post challenge. RESULTS: Data revealed slightly increasing HI titer means reaching the 1st peak at 4 weeks post-vaccination (7.33, 7.67, and 7.33 log2 in the 2nd, 3rd, and 4th groups, respectively), then slightly decreasing and peaked again, giving 9.33 log2 for the2nd group at 3 months post-vaccination (MPV), 10.67 log2 for 3rd the group, and 10.33 log2 for the 4th group at 5 months post-vaccination. Titer gradually decreased but remained protective. The protection rate ranged from 80-100% and 80-90% for homologous and heterologous local RHDV2 vaccines, respectively, within 3 weeks and 6 months post-challenge. The montanide oil RHDV2 vaccine induced better protection than the aluminum gel RHDV2 vaccine. CONCLUSION: The results demonstrated evidence of cross-protection between RHDV2 strains. The oil emulsion vaccine induced higher and longer-lasting antibody titers than those obtained with the RHDV2 aluminum gel vaccine.


Assuntos
Hidróxido de Alumínio , Infecções por Caliciviridae , Vírus da Doença Hemorrágica de Coelhos , Vacinas Virais , Animais , Coelhos , Hidróxido de Alumínio/farmacologia , Hidróxido de Alumínio/administração & dosagem , Vírus da Doença Hemorrágica de Coelhos/imunologia , Vacinas Virais/imunologia , Infecções por Caliciviridae/veterinária , Infecções por Caliciviridae/prevenção & controle , Géis , Adjuvantes Imunológicos/farmacologia , Adjuvantes Imunológicos/administração & dosagem , Vacinas de Produtos Inativados/imunologia , Ácidos Oleicos/farmacologia , Ácidos Oleicos/administração & dosagem
7.
Mycoses ; 67(9): e13793, 2024 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-39239746

RESUMO

Sporotrichosis diagnosis involves a series of analyses, including culture and antibody detection in serum samples. Serologic methods may sometimes yield false-negative or false-positive results, leading to inaccurate diagnoses. This study assessed specific patient groups in which antibody detection of different isotypes and subclasses may lack sensitivity. An enzyme-linked immunosorbent assay (ELISA) with Sporothrix brasiliensis exoantigens was used to investigate IgM, IgG, IgG1, IgG2, IgG3, IgG4, IgA, IgA1 and IgA2 antibodies in human serum samples. Eighty serum samples from patients with different sporotrichosis clinical manifestations, including cutaneous forms with and without hypersensitivity manifestations, extracutaneous forms (bone, ocular, meningeal and pulmonary), disseminated cutaneous forms and disseminated forms in individuals living with HIV/AIDS, diabetics and alcoholics, were evaluated. The ELISA sensitivities in the detection of different antibodies ranged from 0.85 to 0.60 for the detection of IgG2 and IgG3, respectively. The antibodies with higher area under ROC curves were IgG2, IgG, IgA and IgA1. There were no significant differences in the immunological reactivity of the tested antibodies among different clinical forms of sporotrichosis. The data revealed a higher likelihood of a false-negative outcome in patients with lesions in the nasal mucosa regarding the detection of IgM and a lower likelihood in patients with lymphocutaneous sporotrichosis regarding the detection of IgG3. Patients with hypersensitivity manifestations had a 3.71 odds ratio to yield negative results in total IgG detection. In conclusion, we identified specific patient groups in which antibody detection may lack sensitivity, thus contributing to a better understanding of the diagnostic challenges associated with this condition.


Assuntos
Anticorpos Antifúngicos , Ensaio de Imunoadsorção Enzimática , Sensibilidade e Especificidade , Sporothrix , Esporotricose , Humanos , Esporotricose/imunologia , Esporotricose/diagnóstico , Anticorpos Antifúngicos/sangue , Sporothrix/imunologia , Sporothrix/classificação , Masculino , Feminino , Adulto , Pessoa de Meia-Idade , Isotipos de Imunoglobulinas/sangue , Isotipos de Imunoglobulinas/imunologia , Imunoglobulina G/sangue , Idoso , Adulto Jovem , Antígenos de Fungos/imunologia , Antígenos de Fungos/sangue , Imunoglobulina A/sangue , Imunoglobulina M/sangue
8.
Front Immunol ; 15: 1455602, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39234247

RESUMO

Although blood autoantibodies were initially associated with autoimmune diseases, multiple evidence have been accumulated showing their presence in many types of cancer. This has opened their use in clinics, since cancer autoantibodies might be useful for early detection, prognosis, and monitoring of cancer patients. In this review, we discuss the different techniques available for their discovery and validation. Additionally, we discuss here in detail those autoantibody panels verified in at least two different reports that should be more likely to be specific of each of the four most incident cancers. We also report the recent developed kits for breast and lung cancer detection mostly based on autoantibodies and the identification of novel therapeutic targets because of the screening of the cancer humoral immune response. Finally, we discuss unsolved issues that still need to be addressed for the implementation of cancer autoantibodies in clinical routine for cancer diagnosis, prognosis, and/or monitoring.


Assuntos
Autoanticorpos , Biomarcadores Tumorais , Neoplasias , Humanos , Autoanticorpos/imunologia , Autoanticorpos/sangue , Neoplasias/imunologia , Neoplasias/diagnóstico , Biomarcadores Tumorais/imunologia , Prognóstico , Detecção Precoce de Câncer , Animais
9.
Open Vet J ; 14(8): 1794-1800, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-39308706

RESUMO

Background: Natural product active ingredients are currently being studied rigorously worldwide and offer a viable substitute for traditional immunotherapy for various medical disorders. Aim: The objective of the study was to investigate the immunostimulatory properties of fucoidan in albino Wistar rats. Methods: For the current study, forty rats were divided into five groups of rats that were used in good condition. In-vivo experiments of fucoidan were carried out in Wistar albino rats, such as the cyclophosphamide-caused myelosuppression, the delayed-type hypersensitivity (DTH) response, the phagocytic activity, the haemagglutinating antibody (HA) titer, and the neutrophil adhesion test. Results: The phagocytic index increased significantly in response to Fucoidan in a dose-dependent manner, as well as enhanced DTH reaction, and HA titer caused by sheep red blood cells sheep red blood cells. Additionally, fucoidan decreased myelosuppression in rats after cyclophosphamide treatment and enhanced neutrophil adhesion with nylon fiber. Conclusion: These findings imply that fucoidan has immunostimulant properties and could potentially utilised to treat immune-depression diseases.


Assuntos
Adjuvantes Imunológicos , Ciclofosfamida , Imunidade Celular , Imunidade Humoral , Polissacarídeos , Ratos Wistar , Animais , Polissacarídeos/farmacologia , Polissacarídeos/administração & dosagem , Ratos , Imunidade Humoral/efeitos dos fármacos , Ciclofosfamida/farmacologia , Imunidade Celular/efeitos dos fármacos , Adjuvantes Imunológicos/farmacologia , Hipersensibilidade Tardia/imunologia , Hipersensibilidade Tardia/tratamento farmacológico , Fagocitose/efeitos dos fármacos , Masculino , Neutrófilos/efeitos dos fármacos , Neutrófilos/imunologia
10.
Front Immunol ; 15: 1432348, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39301017

RESUMO

Background: This study examines the humoral and cellular response in multiple sclerosis (MS) patients on anti-CD20 therapy before and after the 1st to 4th BNT162b2 mRNA SARS-CoV-2 vaccination and the relationship with breakthrough infection. Methods: Participants with McDonald 2017 MS that were treated with ocrelizumab were included. The study duration was throughout the COVID-19 pandemic until four months after fourth mRNA SARS-CoV-2 vaccination (BNT162b2). Longitudinal blood samples were analysed for: IgG antibodies of SARS-CoV-2 spike anti-receptor binding domain (anti-RBD), nucleocapsid IgG antibodies (anti-N) and activation induced marker expressing CD4+, CD8+ T-cells and concentration of ocrelizumab and anti-drug antibodies. Incidences of breakthrough infection were confirmed with SARS-CoV-2 PCR tests. Results: The rate of anti-RBD positive participants increased substantially between the third and fourth vaccination from 22.2% to 55.9% (median 54.7 BAU/mL; IQR: 14.5 - 221.2 BAU/mL and 607.7 BAU/mL; IQR: 29.4 - 784.6 BAU/mL, respectively). Within the same period 75% of participants experienced breakthrough infection. The fourth vaccination resulted in an additional increase in seropositive individuals (64.3%) (median 541.8 BAU/mL (IQR: 19.1-1007 BAU/mL). Breakthrough infection did not influence the cellular response without a significant change after the fourth vaccination. During the study period two participants had detectable anti-N, both after the fourth vaccination. No correlation was found between serum concentration of ocrelizumab and the humoral and cellular response. Discussion: Low levels or absence of specific anti-RBD following vaccination, with a significant increase after breakthrough infections and boosted by the fourth vaccination. T-cell reactivity remained sustained and unaffected by breakthrough infections.


Assuntos
Anticorpos Antivirais , Vacina BNT162 , COVID-19 , Imunidade Celular , Imunidade Humoral , Esclerose Múltipla , SARS-CoV-2 , Humanos , Masculino , COVID-19/imunologia , COVID-19/prevenção & controle , Feminino , SARS-CoV-2/imunologia , Vacina BNT162/imunologia , Adulto , Pessoa de Meia-Idade , Estudos Longitudinais , Anticorpos Antivirais/sangue , Anticorpos Antivirais/imunologia , Esclerose Múltipla/imunologia , Esclerose Múltipla/tratamento farmacológico , Vacinas contra COVID-19/imunologia , Anticorpos Monoclonais Humanizados/uso terapêutico , Glicoproteína da Espícula de Coronavírus/imunologia , Antígenos CD20/imunologia , Vacinação , Imunoglobulina G/sangue , Imunoglobulina G/imunologia , Infecções Irruptivas
11.
mSphere ; 9(9): e0033024, 2024 Sep 25.
Artigo em Inglês | MEDLINE | ID: mdl-39158304

RESUMO

Outer membrane vesicles (OMVs) from Gram-negative bacteria can be used as a vaccine platform to deliver heterologous antigens. Here, the major protective antigens of Yersinia pestis, F1 and LcrV, were fused either with the leader sequence or the transmembrane domain of the outer membrane protein A (OmpA), resulting in chimeric proteins OmpA-ls-F1V and OmpA46-159-F1V, respectively. We show that OmpA-ls-F1V and OmpA46-159-F1V can be successfully delivered into the lumen and membrane of the OMVs of Escherichia coli, respectively. Mutation of ompA but not tolR in E. coli enhanced the delivery efficiency of OmpA-ls-F1V into OMVs. The OmpA-ls-F1V protein comprises up to 20% of the total protein in OMVs derived from the ompA mutant (OMVdA-ALS-F1V), a proportion significantly higher than the 1% observed for OmpA46-159-F1V in OMVs produced by an ompA mutant that expresses OmpA46-159-F1V, referred to as OMVdA-LATM5-F1V. Intramuscular (i.m.) immunization of mice with OMVdA-ALS-F1V induced significantly higher levels of serum anti-LcrV and anti-F1 IgG, and provided higher efficacy in protection against subcutaneous (s.c.) Y. pestis infection compared to OMVdA-LATM5-F1V and the purified recombinant F1V (rF1V) protein adsorbed to aluminum hydroxide. The three-dose i.m. immunization with OMVdA-ALS-F1V, administered at 14-day intervals, provides complete protection to mice against s.c. infection with 130 LD50 of Y. pestis 201 and conferred 80% against intranasal (i.n.) challenge with 11.4 LD50 of Y. pestis 201. Taken together, our findings indicate that the engineered OMVs containing F1V fused with the leader sequence of OmpA provide significantly higher protection than rF1V against both s.c. and i.n. infection of Y. pestis and more balanced Th1/Th2 responses.IMPORTANCEThe two major protective antigens of Y. pestis, LcrV and F1, have demonstrated the ability to elicit systemic and local mucosal immune responses as subunit vaccines. However, these vaccines have failed to provide adequate protection against pneumonic plague in African green monkeys. Here, Y. pestis F1 and LcrV antigens were successfully incorporated into the lumen and the surface of the outer membrane vesicles (OMVs) of E. coli by fusion either with the leader sequence or the transmembrane domain of OmpA. We compared the humoral immune response elicited by these OMV formulations and their protective efficacy in mice against Y. pestis. Our results demonstrate that the plague OMV vaccine candidates can induce robust protective immunity against both s.c. and i.n. Y. pestis infections, surpassing the effectiveness of rF1V. In addition, immunization with OMVs generated a relatively balanced Th1/Th2 immune response compared to rF1V immunization. These findings underscore the potential of OMVs-based plague vaccines for further development.


Assuntos
Anticorpos Antibacterianos , Antígenos de Bactérias , Proteínas da Membrana Bacteriana Externa , Escherichia coli , Vacina contra a Peste , Peste , Proteínas Citotóxicas Formadoras de Poros , Yersinia pestis , Animais , Peste/prevenção & controle , Peste/imunologia , Antígenos de Bactérias/imunologia , Antígenos de Bactérias/genética , Proteínas da Membrana Bacteriana Externa/imunologia , Proteínas da Membrana Bacteriana Externa/genética , Escherichia coli/genética , Escherichia coli/imunologia , Yersinia pestis/imunologia , Yersinia pestis/genética , Camundongos , Proteínas Citotóxicas Formadoras de Poros/imunologia , Proteínas Citotóxicas Formadoras de Poros/genética , Vacina contra a Peste/imunologia , Vacina contra a Peste/administração & dosagem , Vacina contra a Peste/genética , Feminino , Anticorpos Antibacterianos/sangue , Anticorpos Antibacterianos/imunologia , Camundongos Endogâmicos BALB C , Proteínas Recombinantes de Fusão/imunologia , Proteínas Recombinantes de Fusão/genética , Membrana Externa Bacteriana/imunologia , Proteínas de Bactérias
12.
Biomedicines ; 12(8)2024 Aug 09.
Artigo em Inglês | MEDLINE | ID: mdl-39200275

RESUMO

BACKGROUND: Celiac disease (CD) is an immune-mediated disease characterized by disruptions of the small intestine. Factors such as viral and bacterial infections can trigger CD. Recently, the reactivation of Human Endogenous Retroviruses (HERVs) has also been implicated, but little is known about their specific role in patients with celiac disease. METHODS: The purpose of this study is to explore the humoral immune response mounted against epitopes derived from the envelope portion of three families of HERVs (HERV-K, HERV-H, and HERV-W) in CD patients. Reactivity against the HERV-K, HERV-H, and HERV-W env-su peptides was tested by indirect ELISAs in plasma of 40 patients with celiac disease and 41 age-matched healthy subjects (HCs). RESULTS: HERV-K, HERV-H, and HERV-W env-su peptides triggered different antibody responses in CD patients compared to HCs, with a stronger reactivity (p = 0.0001). CONCLUSIONS: Present results show, for the first time, that epitopes of HERV-K, HERV-H, and HERV-W are more recognized in patients with CD. Taking into consideration their proinflammatory and autoimmune features, this might suggest that HERVs may contribute to the development of CD or its exacerbation in genetically predisposed subjects. Finally, to elucidate the interplay between gut inflammation and HERVs during the inflammatory process, further studies are required. Those investigations should focus on the expression levels of HERVs and their relationship with the immune response, specifically examining anti-transglutaminase 2 (TG2) antibody levels under both gluten-free and gluten-containing dietary conditions.

13.
Antiviral Res ; 230: 105974, 2024 10.
Artigo em Inglês | MEDLINE | ID: mdl-39089331

RESUMO

The outbreak of 2022 monkeypox virus (MPXV) infection in nonendemic regions is a global public health concern. A highly effective and safe MPXV vaccine that is available to the general public is urgently needed to control the mpox pandemic. Here, we developed a multivalent mRNA vaccine candidate, MPXV-1103, which expresses the full-length B6, A35, A29 and M1 proteins with three flexible linkers (G4S1)3 in a single sequence. Compared with the monovalent MPXV mRNA vaccine candidates or the quadrivalent mRNA vaccine from mixtures of the four monovalent MPXV mRNA vaccines, MPXV-1103 elicits a robust humoral response and an MPXV-specific T-cell response and protects mice from lethal vaccinia virus (VACV) challenge, with no live virus detected in the nasal or lungs even at dosages as low as 1 µg. Furthermore, analysis of complete blood counts and photomicrographs of tissue from the main organs of mice vaccinated with MPXV-1103 at doses of 5 µg and 20 µg revealed that two doses of MPXV-1103 did not cause any observable pathological changes in the mice. Collectively, our results suggest that MPXV-1103, with features of high efficacy, safety and a simplified manufacturing process, is a promising vaccine candidate for defending against MPXV infection.


Assuntos
Anticorpos Antivirais , Camundongos Endogâmicos BALB C , Vaccinia virus , Vacinas de mRNA , Animais , Camundongos , Vaccinia virus/imunologia , Vaccinia virus/genética , Feminino , Anticorpos Antivirais/sangue , Anticorpos Antivirais/imunologia , Vacínia/prevenção & controle , Vacínia/imunologia , Mpox/prevenção & controle , Mpox/imunologia , Vacinas Sintéticas/imunologia , Vacinas Sintéticas/administração & dosagem , Monkeypox virus/imunologia , Linfócitos T/imunologia , Imunidade Humoral
14.
Antibodies (Basel) ; 13(3)2024 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-39189240

RESUMO

Malaria is a serious health problem worldwide affecting mainly children and socially vulnerable people. The biological particularities of P. vivax, such as the ability to generate dormant liver stages, the rapid maturation of gametocytes, and the emergence of drug resistance, have contributed to difficulties in disease control. In this context, developing an effective vaccine has been considered a fundamental tool for the efficient control and/or elimination of vivax malaria. Although recombinant proteins have been the main strategy used in designing vaccine prototypes, synthetic immunogenic peptides have emerged as a viable alternative for this purpose. Considering, therefore, that in the Brazilian endemic population, little is known about the profile of the humoral immune response directed to synthetic peptides that represent different P. vivax proteins, the present work aimed to map the epitope-specific antibodies' profiles to synthetic peptides representing the linear portions of the ookinete and sporozoite cell passage protein (CelTOS), thrombospondin-related adhesive protein (TRAP), and cysteine-rich protective antigen (CyRPA) proteins in the acute (AC) and convalescent phases (Conv30 and Conv180 after infection) of vivax malaria. The results showed that the studied subjects responded to all proteins for at least six months following infection. For IgM, a few individuals (3-21%) were positive during the acute phase of the disease; the highest frequencies were observed for IgG (28-57%). Regarding the subclasses, IgG2 and IgG3 stood out as the most prevalent for all peptides. During the follow-up, the stability of IgG was observed for all peptides. Only one significant positive correlation was observed between IgM and exposure time. We conclude that for all the peptides, the immunodominant epitopes are recognized in the exposed population, with similar frequency and magnitude. However, if the antibodies detected in this study are potential protectors, this needs to be investigated.

15.
Int J Mol Sci ; 25(14)2024 Jul 16.
Artigo em Inglês | MEDLINE | ID: mdl-39063007

RESUMO

In order to supplement the research gap concerning Salvia miltiorrhiza polysaccharide extracted from Danshen in NMR analysis, and to clarify its immune enhancement effect as an adjuvant, we isolated and purified SMPD-2, which is composed of nine monosaccharides such as Ara, Gal, and Glc from Danshen. Its weight average molecular weight was 37.30 ± 0.096 KDa. The main chain was mainly composed of →4)-α-D-Galp-(1→, →3,6)-ß-D-Glcp-(1→ and a small amount of α-L-Araf-(1→. After the subcutaneous injection of SMPD-2 as an adjuvant to OVA in mice, we found that it enhanced the immune response by activating DCs from lymph nodes, increasing OVA-specific antibody secretion, stimulating spleen lymphocyte activation, and showing good biosafety. In conclusion, SMPD-2 could be a promising candidate for an adjuvant.


Assuntos
Adjuvantes Imunológicos , Imunidade Celular , Imunidade Humoral , Raízes de Plantas , Polissacarídeos , Salvia miltiorrhiza , Animais , Salvia miltiorrhiza/química , Adjuvantes Imunológicos/farmacologia , Adjuvantes Imunológicos/química , Polissacarídeos/química , Polissacarídeos/farmacologia , Camundongos , Imunidade Humoral/efeitos dos fármacos , Imunidade Celular/efeitos dos fármacos , Raízes de Plantas/química , Feminino , Vacinas/imunologia , Camundongos Endogâmicos BALB C , Baço/efeitos dos fármacos , Baço/imunologia
16.
Toxicon ; 247: 107843, 2024 Aug 28.
Artigo em Inglês | MEDLINE | ID: mdl-38964621

RESUMO

BACKGROUND: Taiwan habu (Protobothrops mucrosquamatus), green bamboo viper (Viridovipera stejnegeri), and Taiwan cobra (Naja atra) are the most venomous snakebites in Taiwan. Patients commonly present with limb swelling but misdiagnosis rates are high, and currently available diagnostic tools are limited. This study explores the immune responses in snakebite patients to aid in differential diagnosis. METHODS: This prospective observational study investigated the changes in cytokines in snakebite patients and their potential for diagnosis. RESULTS: Elevated pro-inflammatory cytokines IL-6 and TNF-α were observed in all snakebite patients compared to the healthy control group. While no significant disparities were observed in humoral immune response cytokines, there were significant differences in IFN-γ levels, with significantly higher IL-10 levels in patients bitten by cobras. Patients with TNF-α levels exceeding 3.02 pg/mL were more likely to have been bitten by a cobra. CONCLUSION: This study sheds light on the immune responses triggered by various venomous snakebites, emphasizing the potential of cytokine patterns for snakebite-type differentiation. Larger studies are needed to validate these findings for clinical use, ultimately improving snakebite diagnosis and treatment.


Assuntos
Citocinas , Mordeduras de Serpentes , Humanos , Taiwan , Animais , Citocinas/sangue , Estudos Prospectivos , Adulto , Masculino , Pessoa de Meia-Idade , Feminino , Fator de Necrose Tumoral alfa , Viperidae , Interleucina-6/sangue , Idoso
17.
Artigo em Inglês | MEDLINE | ID: mdl-38953876

RESUMO

Summary: Background. Papular Urticaria (PU) is a cutaneous hypersensitivity disorder triggered by hematophagous arthropod bites. Despite being a common condition, especially in tropical environments, many knowledge gaps are observed for this disease. The main objective of this study was to investigate the patterns of humoral immune response to mosquito antigens in children with PU and establish a correlation between this response and the severity of clinical symptoms. Methods. An analytical cross-sectional observational study was carried out. Clinical and sociodemographic data and children's blood samples were collected to measure the specific antibodies from: 1. A. aegypti salivary gland antigens; 2. A. aegypti whole body antigens (both produced in the laboratory of the Center for Health Sciences at the Federal University of Rio de Janeiro). A PU severity score based on clinical data is proposed to correlate disease severity with antibody reactivity signatures. Results. According to the clinical data, 58.9% of children received high severity scores. A significant statistical correlation was found between patients with high PU severity score and the development of symptoms before the age of two (p = 0.0326) and high IgG4 anti-salivary gland antigens concentration (p less than 0.05). Conclusion. It is suggested that PU severity in children is associated with a high concentration of IgG4 anti-salivary gland antigens from Aedes aegypti. Further studies are recommended to deepen the understanding of the mechanisms involved.

18.
Heliyon ; 10(11): e31731, 2024 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-38828333

RESUMO

Objective: To monitor post-vaccination antibody production, neutralizing activity, and their dynamics over time in people living with HIV (PLWH). Methods: We collected sera from 147 PLWH and 94 healthy controls after vaccination at different time points and examined changes in antibody levels and neutralizing activity using enzyme-linked immunosorbent assay (ELISA) and pseudovirus neutralization assay. Results: IgG levels were substantially increased in both PLWH and healthy controls after the booster injection. Antibody levels decreased significantly in both PLWH and controls five months after the booster injection. However, the rate of decrease was not significantly different between the two groups. The generated antibodies demonstrated protective efficacy against the wild-type SARS-CoV-2 strain, but very low protection against the mutant strains. Furthermore, the protection decreased over time. The vaccine was less effective in PLWH with <200/µl CD4 T cells. During the SARS-CoV-2 recovery period, participants had substantially increased serum antibody levels and protective efficacy compared with those who received the booster. Conclusion: Both PLWH and controls demonstrated comparable antibody production ability. Vaccines and booster development against SARS-CoV-2 mutant strains should be prioritized in PLWH, especially in those with low CD4 counts.

19.
Vet Immunol Immunopathol ; 274: 110802, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-38924873

RESUMO

Controlling pathogenic infections while reducing antibiotic usage is an important challenge during poultry production. In addition to vaccination strategies, several solutions to enhance the immune response against pathogens are evaluated. In this study, we aim to determine the effects of the glycerides of lauric acid (GLA) supplementation in chickens' diets on humoral and cellular immune response pathogenic infections, using an in vivo model of infectious bronchitis virus (IBV). One-day-old Ross 308 broilers were vaccinated with live attenuated IBV and fed diets supplemented with or without GLA at 3 kg/ton. The levels of early (day 7) specific anti-IBV in sera were significantly increased in broilers fed GLA, compared to the control groups (P<0.05), showing a stronger primary humoral response. The secretion levels of main cytokines remained similar in spleens of all the experimental groups. However, the splenocytes from broilers fed GLA showed higher activation and effector abilities when measured by IFN-γ ELISpot in presence of N-261-280 IBV peptide or Concanavalin A (Con A), a pan T lymphocytes mitogen. In response to N-261-280 peptide, GLA group showed a 2-fold increase of spot numbers (P < 0.05) and 3-fold increase of spot surfaces (P < 0.01) compared to the control groups. Similarly, Con A stimulation showed a 2-fold increases in spot surfaces and numbers in the GLA supplemented group compared to the control group (P < 0.01). In summary, GLA supplementation in chicken feed enhances the primary humoral immune response and strengthen the T lymphocytes mediated cellular immune response. These findings demonstrate how GLA can improve chicken resilience against pathogenic challenges by enhancing their immune responses.


Assuntos
Galinhas , Infecções por Coronavirus , Suplementos Nutricionais , Imunidade Celular , Imunidade Humoral , Vírus da Bronquite Infecciosa , Ácidos Láuricos , Doenças das Aves Domésticas , Animais , Galinhas/imunologia , Vírus da Bronquite Infecciosa/imunologia , Imunidade Humoral/efeitos dos fármacos , Imunidade Celular/efeitos dos fármacos , Doenças das Aves Domésticas/imunologia , Doenças das Aves Domésticas/prevenção & controle , Doenças das Aves Domésticas/virologia , Infecções por Coronavirus/veterinária , Infecções por Coronavirus/imunologia , Infecções por Coronavirus/prevenção & controle , Ácidos Láuricos/farmacologia , Ácidos Láuricos/administração & dosagem , Glicerídeos/farmacologia , Ração Animal/análise , Vacinas Virais/imunologia , Vacinas Virais/administração & dosagem , Anticorpos Antivirais/sangue , Dieta/veterinária , Citocinas/sangue
20.
Vaccines (Basel) ; 12(6)2024 Jun 16.
Artigo em Inglês | MEDLINE | ID: mdl-38932392

RESUMO

Immunosuppressed individuals, such as people living with HIV (PLWH), remain vulnerable to severe COVID-19. We analyzed the persistence of specific SARS-CoV-2 humoral and cellular immune responses in a retrospective, cross-sectional study in PLWH on antiretroviral therapy. Among 104 participants, 70.2% had anti-S IgG antibodies, and 55.8% had significant neutralizing activity against the Omicron variant in a surrogate virus neutralization test. Only 38.5% were vaccinated (8.76 ± 4.1 months prior), all displaying anti-S IgG, 75% with neutralizing antibodies and anti-S IgA. Overall, 29.8% of PLWH had no SARS-CoV-2 serologic markers; they displayed significantly lower CD4 counts and higher HIV viral load. Severe immunosuppression (present in 12.5% of participants) was linked to lower levels of detectable anti-S IgG (p = 0.0003), anti-S IgA (p < 0.0001) and lack of neutralizing activity against the Omicron variant (p < 0.0001). T-cell responses were present in 86.7% of tested participants, even in those lacking serological markers. In PLWH without severe immunosuppression, neutralizing antibodies and T-cell responses persisted for up to 9 months post-infection or vaccination. Advanced immunosuppression led to diminished humoral immune responses but retained specific cellular immunity.

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