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1.
Comput Biol Chem ; 83: 107157, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31751887

RESUMO

Leishmaniosis, caused by intracellular parasites of the genus Leishmania, has become a serious public health problem around the world, and for which there are currently extensive limitations. In this work, a theoretical model was proposed for the development of a multi-epitope vaccine. The protein GP63 of the parasite was selected for epitopes prediction, due to its important biological role for the infection process and abundance. IEDB tools were used to determine epitopes B and T in Leishmania braziliensis; besides, other conserved epitopes in three species were selected. To improve immunogenicity, 50S ribosomal protein L7 / L12 (ID: P9WHE3) was used as a domain of adjuvant in the assembly process. The folding arrangement of the vaccine was obtained through homologous modeling multi-template with MODELLER v9.21, and a Ramachandran plot analysis was done. Furthermore, physicochemical properties were described with the ProtParam tool and secondary structure prediction combining GOR-IV and SOPMA tools. Finally, a molecular dynamics simulation (50 ns) was performed to establish flexibility and conformational changes. The analysis of the results indicates high conservancy in the epitopes predicted among the four species. Moreover, Ramachandran plot, physicochemical parameters, and secondary structure prediction suggest a stable conformation of the vaccine, after a minimum conformational change that was evaluated with the free energy landscape. The conformational change does not drive any substantial change for epitope exposition on the surface. The vaccine proposed could be tested experimentally to guide new approaches in the development of pan-vaccines; vaccines with regions conserved in multiple species.


Assuntos
Leishmania/imunologia , Metaloendopeptidases/imunologia , Simulação de Dinâmica Molecular , Vacinas/imunologia , Epitopos/química , Epitopos/imunologia , Metaloendopeptidases/química , Conformação Proteica , Especificidade da Espécie
2.
J Agric Food Chem ; 67(47): 13127-13138, 2019 Nov 27.
Artigo em Inglês | MEDLINE | ID: mdl-31682438

RESUMO

Allergen-specific immunotherapy is the only available curative treatment for IgE-mediated allergen diseases. A safe hypoallergenic allergen derivative with high efficiency is required as a tolerogen to induce immune tolerance to the causitive allergens. In this study, to generate a rice-based oral allergy vaccine for Japanese cedar (JC) pollinosis, the tertiary structures of major JC pollen allergens, Cry j 1 and Cry j 2, were more completely destructed by shuffling than the previous ones without losing immunogenicity and then were specifically expressed in the endosperm of transgenic rice seed. They accumulated at high levels and were deposited in endoplasmic reticulum (ER) and ER-derived protein bodies. The low allergenicity of these deconstructed Cry j 1 and Cry j 2 allergens was evaluated by examining their binding activities to the specific IgE antibody and by the basophil degranulation test.


Assuntos
Antígenos de Plantas/imunologia , Cryptomeria/imunologia , Hipersensibilidade/imunologia , Oryza/genética , Plantas Geneticamente Modificadas/genética , Animais , Antígenos de Plantas/genética , Cryptomeria/genética , Humanos , Hipersensibilidade/terapia , Imunoterapia , Camundongos , Oryza/metabolismo , Plantas Geneticamente Modificadas/metabolismo , Pólen/genética , Pólen/imunologia , Ratos , Sementes/genética , Sementes/imunologia , Vacinas/administração & dosagem , Vacinas/genética , Vacinas/imunologia
3.
Nature ; 575(7781): 119-129, 2019 11.
Artigo em Inglês | MEDLINE | ID: mdl-31695203

RESUMO

Vaccination against infectious diseases has changed the future of the human species, saving millions of lives every year, both children and adults, and providing major benefits to society as a whole. Here we show, however, that national and sub-national coverage of vaccination varies greatly and major unmet needs persist. Although scientific progress opens exciting perspectives in terms of new vaccines, the pathway from discovery to sustainable implementation can be long and difficult, from the financing, development and licensing to programme implementation and public acceptance. Immunization is one of the best investments in health and should remain a priority for research, industry, public health and society.


Assuntos
Desenvolvimento de Medicamentos/economia , Vacinação/tendências , Vacinas/imunologia , Vacinas/provisão & distribução , Animais , Humanos , Mortalidade , Filipinas/epidemiologia , Mudança Social , Vacinação/economia , Vacinas/economia
4.
Mol Immunol ; 114: 651-660, 2019 10.
Artigo em Inglês | MEDLINE | ID: mdl-31557626

RESUMO

Brucella poses a serious threat to human health. High quality vaccines for Brucella are urgently needed to effectively reduce the incidence of brucellosis. OMP2b and BCSP31 are important component proteins of the Brucella outer membrane and are highly immunogenic. Here, we used the bioinformatics software ProtParam, SOPMA, SWISS-MODEL, Rasmol, BepiPred, SYFPEITHI and IEDB to analyze the structure of these two proteins and predict the epitopes of T cells and B cells. Through analysis, we predicted three Th cell epitopes, seven CTL epitopes, eight B cell epitopes, and one T-B combined epitope of OMP2b protein. Subsequently, we also obtained three Th cell epitopes, six CTL epitopes, nine B cell epitopes and one T-B combined epitope of BCSP31 protein. The T-B combined epitopes and CTL epitopes of OMP2b and those of BCSP31 were synthesized to detect their immunogenicity. The IFN-γ ELISPOT assay showed that the T-B combined epitope peptides of OMP2b and BCSP31 activated Th cell immune responses. ELISA analysis detected the specific antibodies against the T-B combined epitope peptide of OMP2b and BCSP31 in the serum of Brucellosis patients. Additionally, CTL epitope peptide of OMP2b and BCSP31 proteins promoted the secretion of soluble perforin and granzyme B in the culture supernatant. In conclusion, our study shows that the T-B combined epitopes and CTL epitopes of OMP2b and BCSP31 have immunogenicity and immunoreactivity. Our results may lay a theoretical foundation for the development of vaccines against Brucella.


Assuntos
Proteínas de Bactérias/imunologia , Brucella/imunologia , Brucelose/imunologia , Epitopos/imunologia , Porinas/imunologia , Vacinas/imunologia , Adolescente , Adulto , Antígenos de Bactérias/imunologia , Biologia Computacional/métodos , ELISPOT/métodos , Epitopos de Linfócito T/imunologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Adulto Jovem
5.
Eur J Pharm Biopharm ; 145: 1-6, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31560955

RESUMO

Both Gram-positive and Gram-negative bacteria can release nano-sized lipid bilayered structures, known as membrane vesicles (MVs). These MVs play an important role in bacterial survival by orchestrating interactions between bacteria and between bacteria and host. The major constituents of MVs are proteins, lipids and nucleic acids. Due to the immunogenicity of the membrane lipids and/or proteins of the MVs, in combination with adjuvant danger signals and the repeating patterns on the nanosized surface, MVs can effectively stimulate the innate and adaptive immune system. Since they are non-replicating, they are safer than attenuated vaccines. In addition, by genetic engineering of the donor cells, further improvements to their safety profile, immunogenicity and yield can be achieved. To date, one MV-based vaccine against Neisseria meningitidis (N. meningitidis) serogroup B was approved. Other (engineered) MVs in the pipeline study are mostly in the preclinical phase.


Assuntos
Bactérias/imunologia , Bicamadas Lipídicas/imunologia , Lipídeos de Membrana/imunologia , Membranas/imunologia , Vacinas/imunologia , Imunidade Adaptativa/imunologia , Adjuvantes Imunológicos , Animais , Formação de Anticorpos/imunologia , Proteínas de Bactérias/imunologia , Humanos
6.
Int Arch Allergy Immunol ; 180(3): 173-181, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31537004

RESUMO

Allergic diseases affect more than 25% of the global population. Der p 2 is the major allergen of the house dust mite (HDM) Dermatophagoides pteronyssinus. Allergen-specific immunotherapy is the only treatment to change the course of allergic diseases. In this study, two synthesized Der p 2 peptides coupled to cross-reacting material 197 (CRM197) showed reduced IgE reactivity and allergenic activity. CRM197-coupled Der p 2 peptides induced rDer p 2-specific IgG1 antibodies in mice, which could inhibit HDM-allergic patients' IgE binding to rDer p 2. The immunity effects of CRM197-coupled Der p 2 peptides were studied in an rDer p 2-induced asthma mouse model. CRM197-coupled Der p 2 peptides can suppress asthmatic airway inflammation in this model. Analysis of IL-4, IL-5, and IFN-γ levels in bronchoalveolar lavage fluid revealed that the suppression was associated with a shift from a Th2 to a Th1 response. Thus, CRM197-bound Der p 2 peptides exhibited less allergenic activity than the rDer p 2 allergen, which preserved immunogenicity and may be candidates for mite allergy vaccines.


Assuntos
Antígenos de Dermatophagoides/imunologia , Proteínas de Artrópodes/imunologia , Asma/terapia , Proteínas de Bactérias/imunologia , Inflamação/terapia , Pulmão/imunologia , Peptídeos/imunologia , Hipersensibilidade Respiratória/terapia , Animais , Antígenos de Dermatophagoides/química , Proteínas de Artrópodes/química , Asma/imunologia , Proteínas de Bactérias/química , Citocinas/metabolismo , Modelos Animais de Doenças , Feminino , Humanos , Imunoglobulina E/metabolismo , Imunoglobulina G/metabolismo , Inflamação/imunologia , Camundongos , Camundongos Endogâmicos BALB C , Peptídeos/química , Hipersensibilidade Respiratória/imunologia , Equilíbrio Th1-Th2 , Vacinas/imunologia
7.
PLoS Negl Trop Dis ; 13(9): e0007730, 2019 09.
Artigo em Inglês | MEDLINE | ID: mdl-31525197

RESUMO

BACKGROUND: The current strategy for the elimination of onchocerciasis is based on annual or bi-annual mass drug administration with ivermectin. However, due to several limiting factors there is a growing concern that elimination of onchocerciasis cannot be achieved solely through the current strategy. Additional tools are critically needed including a prophylactic vaccine. Presently Ov-103 and Ov-RAL-2 are the most promising vaccine candidates against an Onchocerca volvulus infection. METHODOLOGY/PRINCIPAL FINDINGS: Protection induced by immunization of mice with the alum-adjuvanted Ov-103 or Ov-RAL-2 vaccines appeared to be antibody dependent since AID-/- mice that could not mount antigen-specific IgG antibody responses were not protected from an Onchocerca volvulus challenge. To determine a possible association between antigen-specific antibody responses and anti-larvae protective immunity in humans, we analyzed the presence of anti-Ov-103 and anti-Ov-RAL-2 cytophilic antibody responses (IgG1 and IgG3) in individuals classified as putatively immune, and in infected individuals who developed concomitant immunity with age. It was determined that 86% of putatively immune individuals and 95% individuals with concomitant immunity had elevated IgG1 and IgG3 responses to Ov-103 and Ov-RAL-2. Based on the elevated chemokine levels associated with protection in the Ov-103 or Ov-RAL-2 immunized mice, the profile of these chemokines was also analyzed in putatively immune and infected individuals; both groups contained significantly higher levels of KC, IP-10, MCP-1 and MIP-1ß in comparison to normal human sera. Moreover, human monospecific anti-Ov-103 antibodies but not anti-Ov-RAL-2 significantly inhibited the molting of third-stage larvae (L3) in vitro by 46% in the presence of naïve human neutrophils, while both anti-Ov-103 and anti-Ov-RAL-2 antibodies significantly inhibited the molting by 70-80% when cultured in the presence of naive human monocytes. Interestingly, inhibition of molting by Ov-103 antibodies and monocytes was only in part dependent on contact with the cells, while inhibition of molting with Ov-RAL-2 antibodies was completely dependent on contact with the monocytes. In comparison, significant levels of parasite killing in Ov-103 and Ov-RAL-2 vaccinated mice only occurred when cells enter the parasite microenvironment. Taken together, antibodies to Ov-103 and Ov-RAL-2 and cells are required for protection in mice as well as for the development of immunity in humans. CONCLUSIONS/SIGNIFICANCE: Alum-adjuvanted Ov-103 and Ov-RAL-2 vaccines have the potential of reducing infection and thus morbidity associated with onchocerciasis in humans. The development of cytophilic antibodies, that function in antibody-dependent cellular cytotoxicity, is essential for a successful prophylactic vaccine against this infection.


Assuntos
Imunogenicidade da Vacina , Onchocerca volvulus/imunologia , Oncocercose/imunologia , Vacinas/imunologia , Adjuvantes Imunológicos/administração & dosagem , Compostos de Alúmen , Animais , Anticorpos Anti-Helmínticos/imunologia , Antígenos de Helmintos/imunologia , Quimiocinas/sangue , Imunoglobulina G/sangue , Larva/crescimento & desenvolvimento , Larva/imunologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Monócitos , Onchocerca volvulus/crescimento & desenvolvimento , Oncocercose/parasitologia , Oncocercose/prevenção & controle , Vacinação , Vacinas/administração & dosagem
8.
Curr Top Med Chem ; 19(23): 2158-2175, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31483231

RESUMO

The occurrence of somatic substitution mutations of the KRAS proto-oncogene is highly prevalent in certain cancer types, which often leads to constant activation of proliferative pathways and subsequent neoplastic transformation. It is often seen as a gateway mutation in carcinogenesis and has been commonly deemed as a predictive biomarker for poor prognosis and relapse when conventional chemotherapeutics are employed. Additionally, its mutational status also renders EGFR targeted therapies ineffective owing to its downstream location. Efforts to discover new approaches targeting this menacing culprit have been ongoing for years without much success, and with incidences of KRAS positive cancer patients being on the rise, researchers are now turning towards immunotherapies as the way forward. In this scoping review, recent immunotherapeutic developments and advances in both preclinical and clinical studies targeting K-ras directly or indirectly via its downstream signal transduction machinery will be discussed. Additionally, some of the challenges and limitations of various K-ras targeting immunotherapeutic approaches such as vaccines, adoptive T cell therapies, and checkpoint inhibitors against KRAS positive cancers will be deliberated.


Assuntos
Antineoplásicos Imunológicos/farmacologia , Imunoterapia , Mutação , Neoplasias/terapia , Proteína Oncogênica p21(ras)/antagonistas & inibidores , Linfócitos T/imunologia , Vacinas/imunologia , Animais , Humanos , Neoplasias/genética , Neoplasias/imunologia , Proteína Oncogênica p21(ras)/genética , Proteína Oncogênica p21(ras)/imunologia
9.
Mol Immunol ; 114: 216-225, 2019 10.
Artigo em Inglês | MEDLINE | ID: mdl-31386978

RESUMO

C-type lectin-like domain containing proteins (CTLDcps) mainly bind carbohydrate-based ligands, but also other ligands. CTLDcps are involved in several biological processes including cell adhesion, cell-cell interactions, and pathogen recognition. Pathogen recognition by myeloid cells, e.g. dendritic cells (DCs), can be facilitated through cell surface expressed CTLDcps. Cell surface expressed CTLDcps have been exploited in vaccine designs for specific targeting of human and mouse DCs using antibodies. In recent years, however, DC targeting using carbohydrate-based vaccines has gained interest due to low production cost, limited immunogenicity, and possibility of multivalent adjustment. In chicken, however, only a few CTLDcps have been identified. Identifying and annotating additional chicken CTLDcps (chCTLDcps) is needed to exploit carbohydrate-mediated DC targeting in chicken. Therefore, we searched the chicken GRCg6a assembly for novel chCTLDcps. We identified 28 chCTLDcps of which 10 had previously been described and also experimentally validated. RNA-seq and RT-qPCR confirmed mRNA expression of the remaining 18 identified chCTLDcps. A group of highly related chCTLDcps, moreover, was shown to be avian-specific and comprise novel members mapped to the proposed chicken natural killer gene complex. Two chCTLDcps, chCLEC17AL-A and chCLEC17AL-B, were found to share a recent common ancestor with CLEC17A. Putative mannose or fucose-binding sequence motifs, EPN and WND, were found in the CTLD of chCLEC17AL-A. Both contained intracellular internalisation and signalling sequence motifs. In conclusion, several chCTLDcps were identified and their expression confirmed. Both chCLEC17AL-A and -B showed promise as potential targets in carbohydrate-based chicken vaccine strategies. Determination of DC-specific expression of chCLEC17AL-A and -B, thus, might prove useful in chicken vaccinology.


Assuntos
Carboidratos/imunologia , Lectinas Tipo C/imunologia , Lectinas Tipo C/metabolismo , Vacinas/imunologia , Sequência de Aminoácidos , Animais , Galinhas , Células Dendríticas/imunologia , Feminino , Humanos , Ligantes , Camundongos , Células Mieloides/imunologia
10.
J Anim Sci ; 97(10): 4160-4170, 2019 Oct 03.
Artigo em Inglês | MEDLINE | ID: mdl-31353402

RESUMO

Fescue toxicosis is a multifaceted syndrome common in cattle grazing endophyte-infected tall fescue that affects performance; however, little information is available pertaining to its effects on immunity. Recently, it has been shown that supplemental CP can improve performance in weaned steers postvaccination. Thus, the objective of this study was to evaluate the effect of supplemental CP on innate and adaptive immune responses in stocker steers chronically exposed to ergovaline. Angus steers (n = 12 pens; 3 steers/pen) were stratified by weight and assigned to a 2 × 2 factorial arrangement to examine crude protein levels of supplement (14% or 18%) and ergovaline exposure (0 or 185 µg ergovaline/kg BW/d via ground endophyte-free (EF) or endophyte-infected (EI) tall fescue seed, respectively) on immune response. Consumption of low to moderate concentration of ergovaline from EI tall fescue seed was sufficient to induce mild symptoms associated with fescue toxicosis. Blood samples were collected at day 0, 42, and 56 to evaluate infectious bovine rhinotracheitis (IBR) and bovine viral diarrhea virus (BVDV) type 1b titers following vaccine challenge. Additionally, serum cytokine concentrations were evaluated using Quantibody Bovine Cytokine Arrays on day 0, 28, and 42. Data were analyzed using PROC MIXED of SAS with repeated measures. Regardless of treatment, no differences were observed in IBR and BVDV-1b seroconversion following vaccine challenge (P > 0.05). Regardless of crude protein concentration, EI steers had greater concentrations of proinflammatory cytokines (TNF-α, IFN-γ, IL-1α), chemokines (CCL2, CCL4, MIG), anti-inflammatory cytokines (IL-2, -13, -15, -21), and various growth factors (FGF-1, IGF-1, VEGF-A) when compared to EF steers (P < 0.05). Furthermore, VEGF-A and IGF-1 concentrations were greater in EI-14 steers on day 28 compared to EI-18, EF-14, and EF-18 steers (P < 0.05), however, this difference was not observed on day 0 or 42 (P > 0.05). Based on these data, steers exposed to ergovaline have an increase in pro- and anti-inflammatory cytokines and supplemental CP had minimal impact to mitigate this response. However, in the current study, exposure to ergovaline had little to no effect on adaptive immunity and response to vaccination. Together, chronic exposure to ergovaline results in a hyperactive innate immune response, which may lead to an immuno-compromised animal.


Assuntos
Ração Animal/análise , Bovinos/imunologia , Suplementos Nutricionais/análise , Endófitos/fisiologia , Ergotaminas/farmacologia , Festuca/microbiologia , Imunidade Inata , Intoxicação por Plantas/veterinária , Vacinas/imunologia , Animais , Festuca/química , Masculino
11.
Parasit Vectors ; 12(1): 362, 2019 Jul 25.
Artigo em Inglês | MEDLINE | ID: mdl-31345265

RESUMO

BACKGROUND: Rhipicephalus microplus is a hard tick species that has a high impact on cattle health and production in tropical and subtropical regions. Recently, ribosomal DNA and morphological analysis resulted in the reinstatement of R. australis as a separate species from R. microplus. Both feed on cattle and can transmit bovine pathogens such as Anaplasma and Babesia species. The current treatment with acaricides is becoming increasingly less effective due to the emergence of resistant tick strains. A promising alternative can be found in the form of anti-tick vaccines. The available commercial vaccines can be used to control tick infestation, but the lack of a knockdown effect (> 90% reduction in tick numbers as seen with effective acaricides) hampers its widespread use, hence higher efficacious vaccines are needed. Instead of searching for new protective antigens, we investigated the efficacy of vaccines that contain more than one (partially) protective antigen. For screening vaccine formulations, a previously developed in vitro feeding assay was used in which R. australis larvae are fed sera that were raised against the candidate vaccine antigens. In the present study, the efficacy of the Bm86 midgut antigen and the cytosolic Subolesin (SUB) antigen were evaluated in vitro. RESULTS: Antiserum against recombinant Bm86 (rBm86) partially inhibited larval engorgement, whereas antiserum against recombinant SUB (rSUB) did not have any effect on feeding of larvae. Importantly, when larvae were fed a combination of antiserum against rBm86 and rSUB, a synergistic effect on significantly reducing larval infestations was found. Immunohistochemical analysis revealed that the rBm86 antiserum reacted with gut epithelium of R. australis larvae, whereas the antiserum against rSUB stained salivary glands and rectal sac epithelium. CONCLUSIONS: Combining anti-Bm86 and anti-subolesin antibodies synergistically reduced R. australis larval feeding in vitro. Rhipicephalus australis is a one host tick, meaning that the larvae develop to nymphs and subsequently adults on the same host. Hence, this protective effect could be even more pronounced when larvae are used for infestation of vaccinated cattle, as the antibodies could then affect all three developmental stages. This will be tested in future in vivo experiments.


Assuntos
Anticorpos/farmacologia , Antígenos/imunologia , Proteínas de Artrópodes/imunologia , Soros Imunes/farmacologia , Glicoproteínas de Membrana/imunologia , Rhipicephalus/efeitos dos fármacos , Animais , Antígenos/genética , Proteínas de Artrópodes/genética , Bovinos , Feminino , Larva/efeitos dos fármacos , Larva/fisiologia , Glicoproteínas de Membrana/genética , Proteínas Recombinantes/imunologia , Rhipicephalus/fisiologia , Vacinas/imunologia
12.
PLoS Negl Trop Dis ; 13(6): e0007349, 2019 06.
Artigo em Inglês | MEDLINE | ID: mdl-31166956

RESUMO

Mass drug administration (MDA) is, and has been, the principal method for the control of the schistosome helminths. Using MDA only is unlikely to eliminate the infection in areas of high transmission and the implementation of other measures such as reduced water contact improved hygiene and sanitation are required. Ideally a vaccine is needed to ensure long term benefits and eliminate the need for repeated drug treatment since infection does not seem to induce lasting protective immunity. Currently, a candidate vaccine is under trial in a baboon animal model, and very encouraging results have been reported. In this paper, we develop an individual-based stochastic model to evaluate the effect of a vaccine with similar properties in humans to those recorded in baboons in achieving the World Health Organization (WHO) goals of morbidity control and elimination as a public health problem in populations living in a variety of transmission settings. MDA and vaccination assuming different durations of protection and coverage levels, alone or in combination, are examined as treatment strategies to reach the WHO goals of the elimination of morbidity and mortality in the coming decade. We find that the efficacy of a vaccine as an adjunct or main control tool will depend critically on a number of factors including the average duration of protection it provides, vaccine efficacy and the baseline prevalence prior to immunization. In low prevalence settings, simulations suggest that the WHO goals can be achieved for all treatment strategies. In moderate prevalence settings, a vaccine that provides 5 years of protection, can achieve both goals within 15 years of treatment. In high prevalence settings, by vaccinating at age 1, 6 and 11 we can achieve the morbidity control with a probability of nearly 0.89 but we cannot achieve elimination as a public health problem goal. A combined vaccination and MDA treatment plan has the greatest chance of achieving the WHO goals in the shorter term.


Assuntos
Anti-Helmínticos/administração & dosagem , Transmissão de Doença Infecciosa/prevenção & controle , Administração Massiva de Medicamentos , Modelos Estatísticos , Esquistossomose mansoni/epidemiologia , Esquistossomose mansoni/prevenção & controle , Vacinas/administração & dosagem , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Criança , Pré-Escolar , Terapia Combinada , Humanos , Lactente , Recém-Nascido , Masculino , Pessoa de Meia-Idade , Vacinas/imunologia , Adulto Jovem
13.
Parasitol Res ; 118(7): 2287-2293, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31168702

RESUMO

Schistosomiasis is a devastating disease caused by Schistosoma infection. Glyceraldehyde-3-phosphate dehydrogenase (GAPDH) has emerged as a candidate vaccine component against Schistosoma japonicum, but only confers partial protection. Cytotoxic T lymphocyte antigen-4 (CTLA-4) regulates T cell activation and shows negative effects on vaccine-induced immune protection; however, its potential influence on the protective effects of a GAPDH vaccine against S. japonicum and the underlying mechanism remain unclear. In this study, we established a mouse model of S. japonicum infection, and the mice were randomly divided into uninfected, infected control, anti-CTLA-4 monoclonal antibody (anti-CTLA-4 mAb), GAPDH, and GAPDH combined with anti-CTLA-4 mAb groups to compare the protective effects against infection and the consequent tissue damage. The worm reduction rate in the GAPDH-treated infected mice was 26.58%, which increased to 54.61% when combined with anti-CTLA-4 mAb. The frequency of regulatory T cells (Tregs) was significantly higher in the anti-CTLA-4 mAb group and was lower in the GAPDH group. However, both anti-CTLA-4 mAb and GAPDH elevated the levels of the cytokines IFN-γ, IL-2, IL-4, and IL-5 in the spleens of infected mice, and their combination further enhanced cytokine production. The diameter of egg granuloma in the anti-CTLA-4 mAb group and combined treatment group increased significantly compared to that of the other groups. These results suggest that anti-CTLA-4 mAb can be used as an adjuvant to enhance the immune protection of the GAPDH vaccine via inducing the Th1 immune response, although this comes at the cost of enhanced body injury.


Assuntos
Antígenos de Helmintos/imunologia , Antígeno CTLA-4/imunologia , Gliceraldeído-3-Fosfato Desidrogenases/imunologia , Schistosoma japonicum/imunologia , Esquistossomose Japônica/imunologia , Vacinas/imunologia , Animais , Anticorpos Monoclonais/imunologia , Citocinas/metabolismo , Modelos Animais de Doenças , Feminino , Camundongos , Camundongos Endogâmicos BALB C , Esquistossomose Japônica/parasitologia , Esquistossomose Japônica/prevenção & controle , Baço/imunologia , Linfócitos T Reguladores/imunologia
15.
Proc Jpn Acad Ser B Phys Biol Sci ; 95(6): 290-294, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31189781

RESUMO

Alzheimer's disease (AD) is one of the major causes of chronic and progressive cognitive decline, with the pathological hallmarks of senile plaques and neurofibrillary tangles. Amyloid ß peptide (Aß) is the main component of senile plaques, and the pathological load of Aß in the brain has been shown to be a marker of the severity of AD. To prevent the accumulation of plaques, novel and safer plant-based vaccine strategies have been suggested. In this review, we summarize the results of plant vaccines against Aß.


Assuntos
Doença de Alzheimer/imunologia , Biotecnologia/métodos , Plantas , Vacinas/imunologia , Doença de Alzheimer/prevenção & controle , Animais , Humanos , Plantas/genética , Vacinas/genética
16.
Proc Jpn Acad Ser B Phys Biol Sci ; 95(6): 295-302, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31189782

RESUMO

The herb Ruta chalepensis L. exhibits medical effects, such as anti-inflammatory, central nervous system depressant, and antipyretic activities. However, a genetic transformation method has not yet been developed for this species. In this paper, a simple and efficient tissue culture and genetic transformation system for R. chalepensis is reported. An amyloid ß-peptide (Aß) gene, which is considered to be a causative agent of Alzheimer's disease (AD), fused with green-fluorescent protein (GFP), was introduced into R. chalepensis. When the leaves of R. chalepensis expressing Aß-GFP were administered orally to C57BL/6J mice, serum anti-Aß antibody titers of several mice were elevated without the use of an adjuvant. These results indicated that an oral vaccine against AD using R. chalepensis may be feasible. R. chalepensis is rich in bioactive compounds that may have synergistic effects with the vaccine for AD. Plant-derived vaccines are safer and cheaper than those produced from animal cells or microbes, because plants can serve as biofactories at low cost and with high biosynthetic capacity.


Assuntos
Peptídeos beta-Amiloides/genética , Engenharia Genética/métodos , Proteínas de Fluorescência Verde/genética , Fragmentos de Peptídeos/genética , Proteínas Recombinantes de Fusão/genética , Ruta/genética , Doença de Alzheimer/imunologia , Peptídeos beta-Amiloides/imunologia , Animais , Expressão Gênica , Humanos , Camundongos , Camundongos Endogâmicos C57BL , Fragmentos de Peptídeos/imunologia , Proteínas Recombinantes de Fusão/imunologia , Transformação Genética , Vacinas/genética , Vacinas/imunologia
18.
J Immunol Res ; 2019: 8732191, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31183393

RESUMO

Routine vaccination is among the most effective clinical interventions to prevent diseases as it is estimated to save over 3 million lives every year. However, the full potential of global immunization programs is not realised because population coverage is still suboptimal. This is also due to the inadequate immune response and paucity of informative correlates of protection upon immunization of vulnerable individuals such as newborns, preterm infants, pregnant women, and elderly individuals as well as those patients affected by chronic and immune compromising medical conditions. In addition, these groups are undervaccinated for a number of reasons, including lack of awareness of vaccine-preventable diseases and uncertainty or misconceptions about the safety and efficacy of vaccination by parents and healthcare providers. The presence of these nonresponders/undervaccinated individuals represents a major health and economic burden to society, which will become particularly difficult to address in settings with limited public resources. This review describes innovative and experimental approaches that can help identify specific genomic profiles defining nonresponder individuals for whom specific interventions might be needed. We will provide examples that show how such information can be useful to identify novel biomarkers of safety and immunogenicity for future vaccine trials. Finally, we will discuss how system biology "OMICs" data can be used to design bioinformatic tools to predict the vaccination outcome providing genetic and molecular "signatures" of protective immune response. This strategy may soon enable identification of signatures highly predictive of vaccine safety, immunogenicity, and efficacy/protection thereby informing personalized vaccine interventions in vulnerable populations.


Assuntos
Imunidade/genética , Vacinação , Vacinas/imunologia , Idoso , Biomarcadores , Biologia Computacional , Feminino , Genômica , Humanos , Programas de Imunização , Recém-Nascido , Medicina de Precisão , Gravidez , Resultado do Tratamento
19.
Parasitol Res ; 118(8): 2383-2388, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31203449

RESUMO

In this study, we evaluated in two trials a protocol designed to protect hair sheep using Barbervax®, a vaccine containing Haemonchus contortus gut membrane glycoprotein antigens. Results indicated that naturally infected vaccinated sheep had significant egg count reductions (90.2 ± 4.03%) compared with controls, although blood parameters remained relatively unchanged probably because the level of challenge was low. Vaccination prevented the periparturient rise in egg shedding of ewes, as well as egg shedding in lambs (37.1%). In the second trial, sheep which were experimentally exposed to higher artificial challenge also showed an efficient response to the vaccine as confirmed by high antibody levels and reduced egg counts and worm burdens (87 ± 5.4% and 79%) respectively. Thus, we believe that the vaccine should be integrated with other management practices for meat hair sheep as it has the advantages of adequate efficacy, reducing anthelmintic utilization and avoiding milk and environmental contamination with chemical residues.


Assuntos
Hemoncose/veterinária , Haemonchus/imunologia , Doenças dos Ovinos/prevenção & controle , Vacinação/métodos , Vacinas/administração & dosagem , Animais , Anticorpos Anti-Helmínticos/imunologia , Feminino , Hemoncose/imunologia , Hemoncose/parasitologia , Hemoncose/prevenção & controle , Haemonchus/genética , Contagem de Ovos de Parasitas/veterinária , Ovinos , Doenças dos Ovinos/imunologia , Doenças dos Ovinos/parasitologia , Vacinas/imunologia
20.
J Infect Chemother ; 25(8): 643-645, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31053536

RESUMO

Serological surveillance of pertussis antibodies was performed in 118 children aged 1-12 years. The positivity of pertussis toxin (PT) antibodies was low at 4-6 years and significantly higher at 8-9 years, compared with those at 6 years. Fimbriae 2 (Fim2) antibody showed similar response to the PT antibody. Higher antibody titers against Fim3 were observed among subjects ≥5 years and highest at 8 years. Data demonstrated that the vaccine-induced antibodies decayed by 4-5 years and subclinical pertussis infection was suspected thereafter, suggesting the need for additional dose at around 4-5 years.


Assuntos
Bordetella pertussis/imunologia , Vacinas/imunologia , Coqueluche/imunologia , Anticorpos Antibacterianos/imunologia , Antígenos de Bactérias/imunologia , Criança , Pré-Escolar , Feminino , Proteínas de Fímbrias/imunologia , Fímbrias Bacterianas/imunologia , Humanos , Lactente , Masculino , Toxina Pertussis/imunologia , Vacinação/métodos , Fatores de Virulência de Bordetella/imunologia
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