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1.
Cancer Sci ; 110(10): 3049-3060, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31390678

RESUMO

Heat shock protein 105 (HSP105) is overexpressed in many cancers, including colorectal cancer (CRC) and esophageal cancer (EC). We carried out a phase I clinical trial of HLA-A24- and HLA-A2-restricted HSP105 peptide vaccines in patients with CRC or EC. In this additional study of the trial, we examined the immunological efficacy of the novel vaccine. Thirty patients with advanced CRC or EC underwent HSP105 peptide vaccination. Immunological responses were evaluated by ex vivo and in vitro γ-interferon enzyme-linked immunospot assays and their correlation with patients' prognosis was analyzed. The HSP105 peptide vaccines induced peptide-specific CTLs in 15 of 30 patients. Among HLA-A24 patients (n = 15), 7 showed induction of CTLs only ex vivo, whereas among HLA-A2 patients (n = 15), 4 showed the induction ex vivo and 6 in vitro. Heat shock protein 105-specific CTL induction correlated with suppression of cancer progression and was revealed as a potential predictive biomarker for progression-free survival (P = .008; hazard ratio = 3.03; 95% confidence interval, 1.34-6.85) and overall survival (P = .025; hazard ratio = 2.72; 95% confidence interval, 1.13-6.52). Production of cytokines by HSP105 peptide-specific CTLs was observed at the injection sites (skin) and tumor tissues, suggesting that HSP105-specific CTLs not only accumulated at vaccination sites but also infiltrated tumors. Furthermore, we established 2 HSP105 peptide-specific CTL clones, which showed HSP105-specific cytokine secretion and cytotoxicity. Our results suggest that the HSP105 peptide vaccine could induce immunological effects in cancer patients and improve their prognosis.


Assuntos
Vacinas Anticâncer/administração & dosagem , Neoplasias Colorretais/tratamento farmacológico , Neoplasias Esofágicas/tratamento farmacológico , Proteínas de Choque Térmico HSP110/química , Proteínas de Choque Térmico HSP110/metabolismo , Adulto , Idoso , Vacinas Anticâncer/imunologia , Linhagem Celular Tumoral , Neoplasias Colorretais/imunologia , Citocinas/metabolismo , Intervalo Livre de Doença , Neoplasias Esofágicas/imunologia , Feminino , Antígeno HLA-A2/metabolismo , Antígeno HLA-A24/metabolismo , Células Hep G2 , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , Linfócitos T Citotóxicos/imunologia , Resultado do Tratamento , Vacinas de Subunidades/administração & dosagem , Vacinas de Subunidades/imunologia
2.
Vet Microbiol ; 235: 10-20, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31282366

RESUMO

African Swine Fever Virus (ASFV) causes a hemorrhagic disease in swine and wild boars with a fatality rate close to 100%. Less virulent strains cause subchronic or chronic forms of the disease. The virus is endemic in sub-Saharan Africa and an outbreak in Georgia in 2007 spread to Armenia, Russia, Ukraine, Belarus, Poland, Lithuania, and Latvia. In August 2018, there was an outbreak in China and in April 2019, ASFV was reported in Vietnam and Cambodia. Since no vaccine or treatment exists, a vaccine is needed to safeguard the swine industry. Previously, we evaluated immunogenicity of two adenovirus-vectored cocktails containing ASFV antigens and demonstrated induction of unprecedented robust antibody and T cell responses, including cytotoxic T lymphocytes. In the present study, we evaluated protective efficacy of both cocktails by intranasal challenge of pigs with ASFV-Georgia 2007/1. A nine antigen cocktail-(I) formulated in BioMize adjuvant induced strong IgG responses, but when challenged, the vaccinees had more severe reaction relative to the controls. A seven antigen cocktail-(II) was evaluated using two adjuvants: BioMize and ZTS-01. The BioMize formulation induced stronger antibody responses, but 8/10 vaccinees and 4/5 controls succumbed to the disease or reached experimental endpoint at 17 days post-challenge. In contrast, the ZTS-01 formulation induced weaker antibody responses, but 4/9 pigs succumbed to the disease while the 5 survivors exhibited low clinical scores and no viremia at 17 days post-challenge, whereas 4/5 controls succumbed to the disease or reached experimental endpoint. Overall, none of the immunogens conferred statistically significant protection.


Assuntos
Febre Suína Africana/prevenção & controle , Anticorpos Antivirais/sangue , Antígenos Virais/imunologia , Vacinas Virais/imunologia , Adenoviridae , Administração Intranasal , Febre Suína Africana/imunologia , Vírus da Febre Suína Africana , Animais , Antígenos Virais/genética , Imunoglobulina G/sangue , Suínos , Linfócitos T Citotóxicos/imunologia , Vacinas de Subunidades/imunologia , Proteínas Virais/genética , Proteínas Virais/imunologia , Vacinas Virais/genética , Viremia , Virulência
3.
Protein Pept Lett ; 26(5): 324-331, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31237198

RESUMO

Antimicrobial resistance (AMR) reported to increase globally at alarming levels in the recent past. A number of potential alternative solutions discussed and implemented to control AMR in bacterial pathogens. Stringent control over the clinical application of antibiotics for a reduction in uses is a special consideration along with alternative solutions to fight against AMR. Although alternatives to conventional antibiotics like antimicrobial peptides (AMP) might warrant serious consideration to fight against AMR, there is a thriving recognition for vaccines in encountering the problem of AMR. Vaccines can reduce the prevalence of AMR by reducing the number of specific pathogens, which result in cutting down the antimicrobial need and uses. However, conventional vaccines produced using live or attenuated microorganisms while the presence of immunologically redundant biological components or impurities might cause major side effects and health related problems. Here we discussed AMPs based vaccination strategies as an emerging concept to overcome the disadvantages of traditional vaccines while boosting the AMPs to control multidrug resistant bacteria or AMR. Nevertheless, the poor immune response is a major challenge in the case of peptide vaccines as minimal antigenic epitopes used for immunization in peptide vaccines.


Assuntos
Peptídeos Catiônicos Antimicrobianos/imunologia , Vacinas Bacterianas/imunologia , Adjuvantes Imunológicos , Animais , Peptídeos Catiônicos Antimicrobianos/química , Desenvolvimento de Medicamentos , Farmacorresistência Bacteriana Múltipla , Humanos , Imunidade Inata , Vacinas de Subunidades/imunologia
4.
Eur J Pharm Biopharm ; 140: 29-39, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31055066

RESUMO

Using subunit vaccines, e.g., based on peptide or protein antigens, to teach the immune system to kill abnormal host cells via induction of cytotoxic T lymphocytes (CTL) is a promising strategy against intracellular infections and cancer. However, customized adjuvants are required to potentiate antigen-specific cellular immunity. One strong CTL-inducing adjuvant is the liposomal cationic adjuvant formulation (CAF)09, which is composed of dimethyldioctadecylammonium (DDA) bromide, monomycoloyl glycerol (MMG) analogue 1 and polyinosinic:polycytidylic acid [poly(I:C)]. However, this strong CTL induction requires intraperitoneal administration because the vaccine forms a depot at the site of injection (SOI) after subcutaneous (s.c.) or intramuscular (i.m.) injection, and depot formation impedes the crucial vaccine targeting to the cross-presenting dendritic cells (DCs) residing in the lymph nodes (LNs). The purpose of the present study was to investigate the effect of polyethylene glycol (PEG) grafting of CAF09 on the ability of the vaccine to induce antigen-specific CTL responses after s.c. administration. We hypothesized that steric stabilization and charge shielding of CAF09 by PEGylation may reduce depot formation at the SOI and enhance passive drainage to the LNs, eventually improving CTL induction. Hence, the vaccine (antigen/CAF09) was post-grafted with a novel type of anionic PEGylated peptides based on GDGDY repeats, which were end-conjugated with one or two PEG1000 moieties, resulting in mono- and bis-PEG-peptides of different lengths (10, 15 and 20 amino acid residues). For comparison, CAF09 was also grafted by inclusion of 1,2-distearoyl-sn-glycero-3-phosphoethanolamine-N-methoxy(PEG)-2000 (DSPE-PEG2000) in the bilayer structure during preparation. Grafting of CAF09 with either type of PEG resulted in charge shielding, evident from a reduced surface charge. Upon s.c. immunization of mice with the model antigen ovalbumin (OVA) adjuvanted with PEGylated CAF09, stronger CTL responses were induced as compared to immunization of mice with unadjuvanted OVA. Biodistribution studies confirmed that grafting of CAF09 with DSPE-PEG2000 improved the passive drainage of the vaccine to LNs, because a higher dose fraction was recovered in DCs present in the draining LNs, as compared to the dose fraction detected for non-PEGylated CAF09. In conclusion, PEGylation of CAF09 may be a useful strategy for the design of an adjuvant, which induces CTL responses after s.c. and i.m. administration. In the present studies, CAF09 grafted with 10 mol% DSPE-PEG2000 is the most promising of the tested adjuvants, but additional studies are required to further elucidate the potential of the strategy.


Assuntos
Adjuvantes Imunológicos/química , Adjuvantes Imunológicos/farmacologia , Lipossomos/química , Polietilenoglicóis/química , Linfócitos T Citotóxicos/imunologia , Vacinas de Subunidades/imunologia , Animais , Antígenos/imunologia , Linfócitos T CD8-Positivos/imunologia , Apresentação Cruzada/imunologia , Células Dendríticas/imunologia , Feminino , Imunidade Celular/imunologia , Imunização/métodos , Camundongos , Camundongos Endogâmicos C57BL , Ovalbumina/imunologia , Fosfatidiletanolaminas/química , Compostos de Amônio Quaternário/química , Distribuição Tecidual
5.
Infect Immun ; 87(8)2019 08.
Artigo em Inglês | MEDLINE | ID: mdl-31085705

RESUMO

Lyme disease (LD), the most prevalent vector-borne illness in the United States and Europe, is caused by Borreliella burgdorferi No vaccine is available for humans. Dogmatically, B. burgdorferi can establish a persistent infection in the mammalian host (e.g., mice) due to a surface antigen, VlsE. This antigenically variable protein allows the spirochete to continually evade borreliacidal antibodies. However, our recent study has shown that the B. burgdorferi spirochete is effectively cleared by anti-B. burgdorferi antibodies of New Zealand White rabbits, despite the surface expression of VlsE. Besides homologous protection, the rabbit antibodies also cross-protect against heterologous B. burgdorferi spirochetes and significantly reduce the pathology of LD arthritis in persistently infected mice. Thus, this finding that NZW rabbits develop a unique repertoire of very potent antibodies targeting the protective surface epitopes, despite abundant VlsE, prompted us to identify the specificities of the protective rabbit antibodies and their respective targets. By applying subtractive reverse vaccinology, which involved the use of random peptide phage display libraries coupled with next-generation sequencing and our computational algorithms, repertoires of nonprotective (early) and protective (late) rabbit antibodies were identified and directly compared. Consequently, putative surface epitopes that are unique to the protective rabbit sera were mapped. Importantly, the relevance of newly identified protection-associated epitopes for their surface exposure has been strongly supported by prior empirical studies. This study is significant because it now allows us to systematically test the putative epitopes for their protective efficacy with an ultimate goal of selecting the most efficacious targets for development of a long-awaited LD vaccine.


Assuntos
Anticorpos Antibacterianos/imunologia , Vacinas Bacterianas/imunologia , Borrelia burgdorferi/imunologia , Epitopos , Animais , Antígenos de Bactérias/imunologia , Proteínas da Membrana Bacteriana Externa/imunologia , Proteínas de Bactérias/imunologia , Lipoproteínas/imunologia , Masculino , Camundongos , Camundongos Endogâmicos C3H , Coelhos , Vacinas de Subunidades/imunologia
6.
Vet Microbiol ; 231: 87-92, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30955830

RESUMO

The objective of this study was to compare the efficacy of a commercial porcine circovirus type 2a (PCV2a) subunit vaccine against experimental PCV2a, PCV2b, and PCV2d challenge. A total of 105 pigs were randomly divided into 7 groups (15 pigs per group). At 21 days old the pigs were intramuscularly administered the PCV2a vaccine as a 1.0 mL dose. Four weeks following vaccination, pigs were challenged with either Korean PCV2a, PCV2b, or PCV2d. All vaccinated pigs showed a significant (P < 0.05) reduction of clinical signs, PCV2 viremia, lymphoid lesions, and lymphoid PCV2 antigen levels compared to unvaccinated control pigs. Vaccination resulted also in significantly higher (P < 0.05) titers of neutralizing antibody against PCV2, and an increase in the frequency of PCV2-specific interferon-γ secreting cells (IFN-γ-SC). The vaccine showed similar protection among the vaccinated groups regardless of the genotype of the challenge. Interestingly, vaccinated pigs had higher levels of neutralizing antibody titers against PCV2a compared to PCV2b or PCV2d while the number of PCV2a-, PCV2b-, and PCV2d-specific IFN-γ-SC were similar. Taken together, the results presented here demonstrate that a PCV2a vaccine can be effective against experimental PCV2a, PCV2b, and PCV2d challenge.


Assuntos
Anticorpos Antivirais/sangue , Infecções por Circoviridae/veterinária , Doenças dos Suínos/prevenção & controle , Vacinas Virais/uso terapêutico , Animais , Anticorpos Neutralizantes/sangue , Infecções por Circoviridae/imunologia , Infecções por Circoviridae/prevenção & controle , Circovirus/genética , Circovirus/imunologia , DNA Viral/sangue , Fazendas , Genótipo , Injeções Intramusculares , Interferon gama/imunologia , Gado , Distribuição Aleatória , Suínos , Doenças dos Suínos/imunologia , Vacinação , Vacinas de Subunidades/imunologia , Vacinas de Subunidades/uso terapêutico , Vacinas Virais/imunologia
7.
MBio ; 10(2)2019 04 02.
Artigo em Inglês | MEDLINE | ID: mdl-30940710

RESUMO

Zika virus is a mosquito-borne flavivirus which can cause severe disease in humans, including microcephaly and other congenital malformations in newborns and Guillain-Barré syndrome in adults. There are currently no approved prophylactics or therapeutics for Zika virus; the development of a safe and effective vaccine is an urgent priority. Preclinical studies suggest that the envelope glycoprotein can elicit potently neutralizing antibodies. However, such antibodies are implicated in the phenomenon of antibody-dependent enhancement of disease. We have previously shown that monoclonal antibodies targeting the Zika virus nonstructural NS1 protein are protective without inducing antibody-dependent enhancement of disease. Here, we investigated whether the NS1 protein itself is a viable vaccine target. Wild-type mice were vaccinated with an NS1-expressing DNA plasmid followed by two adjuvanted protein boosters, which elicited high antibody titers. Passive transfer of the immune sera was able to significantly protect STAT2 knockout mice against lethal challenge by Zika virus. In addition, long-lasting NS1-specific IgG responses were detected in serum samples from patients in either the acute or the convalescent phase of Zika virus infection. These NS1-specific antibodies were able to functionally engage Fcγ receptors. In contrast, envelope-specific antibodies did not activate Fc-mediated effector functions on infected cells. Our data suggest that the Zika virus NS1 protein, which is expressed on infected cells, is critical for Fc-dependent cell-mediated immunity. The present study demonstrates that the Zika virus NS1 protein is highly immunogenic and can elicit protective antibodies, underscoring its potential for an effective Zika virus vaccine.IMPORTANCE Zika virus is a global public health threat that causes microcephaly and congenital malformations in newborns and Guillain-Barré syndrome in adults. Currently, no vaccines or treatments are available. While antibodies targeting the envelope glycoprotein can neutralize virus, they carry the risk of antibody-dependent enhancement of disease (ADE). In contrast, antibodies generated against the NS1 protein can be protective without eliciting ADE. The present study demonstrates the effectiveness of an NS1-based vaccine in eliciting high titers of protective antibodies against Zika virus disease in a mouse model. Sera generated by this vaccine can elicit Fc-mediated effector functions against Zika virus-infected cells. Lastly, we provide human data suggesting that the antibody response against the Zika virus NS1 protein is long-lasting and functionally active. Overall, our work will inform the development of a safe and effective Zika virus vaccine.


Assuntos
Anticorpos Antivirais/sangue , Proteínas não Estruturais Virais/imunologia , Vacinas Virais/imunologia , Infecção por Zika virus/prevenção & controle , Animais , Linhagem Celular , Modelos Animais de Doenças , Humanos , Imunidade Celular , Esquemas de Imunização , Imunização Passiva , Imunoglobulina G/sangue , Camundongos , Camundongos Knockout , Receptores Fc/metabolismo , Análise de Sobrevida , Vacinas de DNA/administração & dosagem , Vacinas de DNA/imunologia , Vacinas de Subunidades/administração & dosagem , Vacinas de Subunidades/imunologia , Vacinas Virais/administração & dosagem
8.
J Microbiol Biotechnol ; 29(5): 813-819, 2019 May 28.
Artigo em Inglês | MEDLINE | ID: mdl-30982320

RESUMO

Middle East respiratory syndrome coronavirus (MERS-CoV) induces severe respiratory impairment with a reported mortality rate of ~36% in humans. The absence of clinically available MERS-CoV vaccines and treatments to date has resulted in uncontrolled incidence and propagation of the virus. In vaccine design, fusion with the IgG Fc domain is reported to increase the immunogenicity of various vaccine antigens. However, limited reports have documented the potential negative effects of Fc fusion on vaccine antigens. To determine whether Fc fusion affects the immunogenicity of MERS-CoV antigen, we constructed a Fcassociated MERS-CoV spike protein (eS770-Fc, 110 kDa), whereby human IgG4 Fc domain was fused to MERS-CoV spike protein (eS770) via a Gly/Pro linker using baculovirus as the expression system. For comparative analyses, two eS770 proteins lacking the IgG4 Fc domain were generated using the IdeS protease (eS770-ΔFc) or His tag attachment (eS770-His) and the immunogenicity of the above constructs were examined following intramuscular immunization in mice. Contrary to expectations, non-Fc spike proteins (eS770-ΔFc, eS770-His; 90 kDa) showed higher immunogenicity than the Fc fusion protein (eS770-Fc). Moreover, unlike non- Fc spike proteins, eS770-Fc immunization did not elicit neutralizing antibodies against MERSCoV. The lower immunogenicity of Fc-fused eS770 was related to alterations in the structural conformation of the spike protein. Taken together, our results indicate that IgG Fc fusion reduces the immunogenicity of eS770 by interfering with the proper folding structure.


Assuntos
Infecções por Coronavirus/prevenção & controle , Imunogenicidade da Vacina , Coronavírus da Síndrome Respiratória do Oriente Médio/imunologia , Dobramento de Proteína , Proteínas Recombinantes de Fusão/imunologia , Glicoproteína da Espícula de Coronavírus/imunologia , Vacinas Virais/imunologia , Animais , Anticorpos Neutralizantes , Anticorpos Antivirais , Antígenos Virais/genética , Feminino , Imunização , Fragmentos Fc das Imunoglobulinas/imunologia , Imunoglobulina G , Camundongos , Camundongos Endogâmicos BALB C , Coronavírus da Síndrome Respiratória do Oriente Médio/genética , Coronavírus da Síndrome Respiratória do Oriente Médio/patogenicidade , Testes de Neutralização , Células Sf9 , Glicoproteína da Espícula de Coronavírus/química , Glicoproteína da Espícula de Coronavírus/genética , Vacinação , Vacinas de Subunidades/imunologia , Vacinas Virais/genética
9.
Fish Shellfish Immunol ; 90: 12-19, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31015064

RESUMO

Grass carp reovirus (GCRV) is the main viral pathogen that endangers grass carp seriously. Application of vaccine has been considered to be the most effective way to prevent virus infection. VP56 is a protein encoded by gene segment 7 of grass carp reovirus, and is predicted to share homology with fiber protein of mammalian reovirus (MRV). In our study, the immunogenicity of VP56 was evaluated by neutralization test. GCRV was incubated with mouse anti-VP56 antibody, and then was injected into grass carp. Results showed that disease progress and death occurrence was hindered in the experimental group compared with the control group. For further study, the recombinant VP56 protein (rVP56) expressed by pET-32a (+) vector was purified, and was used as subunit vaccine to immunize grass carp. After each fish (15 ± 1.5 g) was injected with 30 µg purified rVP56 intraperitoneally, the immune protective efficacy of recombinant VP56 protein was assessed by a series of immune parameters. The population of red blood cells in immunized fish increased significantly after 5 d post injection (dpi), and reached a peak with (2.98 ± 0.17) × 109/ml at 7 dpi (p < 0.05). The numbers of white blood cells peaked with (8.42 ±â€¯1.01) × 107/ml at 7 dpi (p < 0.05). Additionally, the percentage of monocytes and neutrophils rose to a peak with (9.05 ±â€¯0.92)% and (25.93 ±â€¯2.60)% respectively at 5 dpi (p < 0.05 or p < 0.01), whereas lymphocytes reached the highest value of (85.81 ±â€¯2.73) % at 14 dpi (p < 0.01). Serum antibody titer in the vaccinated fish increased significantly and reached a peak at 21 dpi (p < 0.01). The mRNA expression levels of type I interferon (IFN1), major histocompatibility complex class I (MHC I), Toll-like receptor 22 (TLR22), and immunoglobulin M (IgM) were significantly up-regulated in head kidney and spleen (p < 0.05 or p < 0.01). The GCRV challenge test showed that the relative survival rate in immunized group was 71%-75%. Collectively, the results indicated that rVP56 protein can induce immune protection in grass carp, and can be consider as a candidate vaccine against GCRV infection.


Assuntos
Carpas , Doenças dos Peixes/prevenção & controle , Infecções por Reoviridae/veterinária , Reoviridae/imunologia , Proteínas Virais/imunologia , Vacinas Virais/imunologia , Animais , Doenças dos Peixes/virologia , Imunidade Inata , Imunogenicidade da Vacina , Distribuição Aleatória , Infecções por Reoviridae/prevenção & controle , Infecções por Reoviridae/virologia , Vacinas de Subunidades/imunologia
10.
Int J Mol Sci ; 20(8)2019 Apr 18.
Artigo em Inglês | MEDLINE | ID: mdl-31003532

RESUMO

Antigen-mimicking peptide (mimotope)-based vaccines are one of the most promising forms of active-immunotherapy. The main drawback of this approach is that it induces antibodies that react poorly with the nominal antigen. The aim of this study was to investigate the molecular basis underlying the weak antibody response induced against the naïve protein after peptide vaccination. For this purpose, we analyzed the fine specificity of monoclonal antibodies (mAb) elicited with a 13-mer linear peptide, complementary to theantigen-combining site of the anti-CD20 mAb, Rituximab, in BALB/c mice. Anti-peptide mAb competed with Rituximab for peptide binding. Even so, they recognized a different antigenic motif from the one recognized by Rituximab. This explains their lack of reactivity with membrane (naïve) CD20. These data indicate that even on a short peptide the immunogenic and antigenic motifs may be different. These findings highlight an additional mechanism for epitope spreading and should be taken into account when designing peptides for vaccine purposes.


Assuntos
Anticorpos Monoclonais/genética , Antígenos CD20/imunologia , Peptídeos/genética , Rituximab/imunologia , Animais , Anticorpos Monoclonais/imunologia , Anticorpos Monoclonais Murinos/genética , Anticorpos Monoclonais Murinos/imunologia , Antígenos CD20/genética , Sítios de Ligação de Anticorpos/genética , Epitopos/genética , Epitopos/imunologia , Humanos , Camundongos , Biblioteca de Peptídeos , Peptídeos/imunologia , Rituximab/genética , Vacinação/métodos , Vacinas de Subunidades/genética , Vacinas de Subunidades/imunologia
11.
Vet Microbiol ; 230: 7-13, 2019 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-30827407

RESUMO

Necrotic enteritis (NE) is an economically important disease of broiler chickens that is caused primarily by Clostridium perfringens strains that produce the NetB toxin. It is controlled in North America principally through the application of in-feed antimicrobials, but alternative control methods, such as vaccination, are urgently needed. We previously identified a cluster of C. perfringens genes prevalent in disease-causing strains, denominated VR-10B, that is predicted to encode a pilus. The current study evaluated the ability of three predicted pilin structural subunits (CnaA, FimA, FimB) to protect against NE in two immunization studies. In the first study, young broiler chickens were immunized twice intramuscularly (i.m.) with CnaA or FimA, which resulted in only a weak serum antibody response, and no reduction in the severity of intestinal lesions following experimental challenge with C. perfringens strain CP1. In the second study, chickens were injected subcutaneously (s.c.) with CnaA, FimB, or a combination of all three proteins, on days 7, 14 and 19, which resulted in a marked antibody response specific to each antigen. Chickens immunized with either CnaA or FimB had significantly reduced NE lesion severity, whereas immunization with all three proteins in combination did not provide protection. Western blot experiments using serum from immunized birds were also performed, providing the first experimental evidence to suggest that this locus may in fact encode a functional pilus structure.


Assuntos
Vacinas Bacterianas/imunologia , Infecções por Clostridium/veterinária , Clostridium perfringens/imunologia , Enterite/veterinária , Proteínas de Fímbrias/imunologia , Doenças das Aves Domésticas/prevenção & controle , Animais , Anticorpos Antibacterianos/sangue , Vacinas Bacterianas/administração & dosagem , Galinhas/imunologia , Infecções por Clostridium/prevenção & controle , Enterite/microbiologia , Enterite/prevenção & controle , Proteínas de Fímbrias/administração & dosagem , Fímbrias Bacterianas/genética , Fímbrias Bacterianas/imunologia , Injeções Intramusculares , Intestinos/patologia , Doenças das Aves Domésticas/microbiologia , Vacinas de Subunidades/administração & dosagem , Vacinas de Subunidades/imunologia
12.
Int J Mol Sci ; 20(6)2019 Mar 13.
Artigo em Inglês | MEDLINE | ID: mdl-30871133

RESUMO

Hand, foot, and mouth disease (HFMD) commonly produces herpangina, but fatal neurological complications have been observed in children. Enterovirus 71 (EV-A71) and Coxsackievirus 16 (CV-A16) are the predominant viruses causing HFMD worldwide. With rising concern about HFMD outbreaks, there is a need for an effective vaccine against EV-A71 and CV-A16. Although an inactivated vaccine has been developed against EV-A71 in China, the inability of the inactivated vaccine to confer protection against CV-A16 infection and other HFMD etiological agents, such as CV-A6 and CV-A10, necessitates the exploration of other vaccine platforms. Thus, the antigenic peptide-based vaccines are promising platforms to develop safe and efficacious multivalent vaccines, while the monoclonal antibodies are viable therapeutic and prophylactic agents against HFMD etiological agents. This article reviews the available information related to the antigenic peptides of the etiological agents of HFMD and their neutralizing antibodies that can provide a basis for the design of future therapies against HFMD etiological agents.


Assuntos
Anticorpos Neutralizantes/imunologia , Doença de Mão, Pé e Boca/imunologia , Peptídeos/imunologia , Vacinas de Subunidades/imunologia , Vacinas Virais/imunologia , Animais , Enterovirus/imunologia , Enterovirus Humano A/imunologia , Humanos
13.
Arch Virol ; 164(6): 1501-1513, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-30888563

RESUMO

Foot-and-mouth disease (FMD) is a major worldwide viral disease in animals, affecting the national and international trade of livestock and animal products and leading to high economic losses and social consequences. Effective control measures of FMD involve prevention through vaccination with inactivated vaccines. These inactivated vaccines, unfortunately, require short-term protection and cold-chain and high-containment facilities. Major advances and pursuit of hot topics in vaccinology and vectorology are ongoing, involving peptide vaccines, DNA vaccines, live vector vaccines, and novel attenuated vaccines. DIVA capability and marker vaccines are very important in differentiating infected animals from vaccinated animals. This review focuses on updating the research progress of these novel vaccines, summarizing their merits and including ideas for improvement.


Assuntos
Vírus da Febre Aftosa/imunologia , Febre Aftosa/prevenção & controle , Gado/virologia , Vacinas Virais/uso terapêutico , Animais , Bovinos , Doenças dos Bovinos/prevenção & controle , Doenças dos Bovinos/virologia , Febre Aftosa/imunologia , Vírus da Febre Aftosa/genética , Doenças dos Cavalos/prevenção & controle , Doenças dos Cavalos/virologia , Cavalos , Ovinos , Doenças dos Ovinos/prevenção & controle , Doenças dos Ovinos/virologia , Vacinas de DNA/imunologia , Vacinas de DNA/uso terapêutico , Vacinas de Produtos Inativados/imunologia , Vacinas de Produtos Inativados/uso terapêutico , Vacinas de Subunidades/imunologia , Vacinas de Subunidades/uso terapêutico , Vacinas de Partículas Semelhantes a Vírus/uso terapêutico , Vacinas Virais/imunologia
14.
Biomater Sci ; 7(5): 1794-1800, 2019 Apr 23.
Artigo em Inglês | MEDLINE | ID: mdl-30888360

RESUMO

Biomedical applications and nanotechnological advances, including constrained synthesis, multimodal imaging, drug delivery, and bioassay, have strongly benefited from employing ferritin nanocages due to their remarkable properties of easy engineering, great biocompatible features, large capacity and so on. In this study, ferritin nanocages were used to display epitopes (model antigens derived from Enterovirus 71 (EV71) with different length) on C- and N-terminals and the loop zone to search for the optimal position for the fusion of the epitopes to the vaccine platform. The longest epitope displayed on the N-terminal and loop zone as well as the second longest peptide displayed on the loop zone of ferritin resulted in 100% passive protection of newborn BALB/c mice from the lethal EV71. This suggests that peptides fused onto the loop zone of ferritin could induce strong immune response. Our results increase the versatility of the vaccine platform and provide more options for the production of stable constructs, suggesting the potential future clinical applicability of ferritin-based antigen delivery nanoplatforms.


Assuntos
Antígenos Virais/química , Portadores de Fármacos/química , Desenho de Drogas , Epitopos/química , Ferritinas/química , Nanoestruturas/química , Sequência de Aminoácidos , Animais , Antígenos Virais/imunologia , Enterovirus/imunologia , Epitopos/imunologia , Imunização , Camundongos , Modelos Moleculares , Conformação Proteica , Vacinas de Subunidades/química , Vacinas de Subunidades/imunologia
15.
Virus Res ; 265: 150-155, 2019 05.
Artigo em Inglês | MEDLINE | ID: mdl-30922809

RESUMO

An outbreak in the Caucasus in 2007 initiated the spread of ASFV through Russia and Eastern Europe, subsequently affecting Ukraine, Belarus, Poland, the Baltic States, the Czech Republic, Moldova, Romania and Bulgaria. The declaration of outbreaks in China and Central Europe in August 2018, definitely confirms the serious threat that the extension of ASF represents for the global swine industry and the environment. Despite the efforts of several groups to generate a vaccine against ASFV, currently only control and eradication measures are available based mainly on the early detection and implementation of strict sanitary procedures, including the mass slaughter of animals, both domestic and wild boar. However, the rapid spread of the disease shows that these actions are clearly insufficient to control the current pandemic situation, and the development of a vaccine is urgently required.


Assuntos
Vírus da Febre Suína Africana/imunologia , Febre Suína Africana/prevenção & controle , Surtos de Doenças/veterinária , Vacinas Virais/imunologia , Animais , China , Surtos de Doenças/prevenção & controle , Europa (Continente) , Federação Russa , Sus scrofa/virologia , Suínos , Vacinas Atenuadas/imunologia , Vacinas de Subunidades/imunologia , Proteínas Virais/imunologia
16.
Eur J Pharm Sci ; 132: 1-17, 2019 Apr 30.
Artigo em Inglês | MEDLINE | ID: mdl-30797936

RESUMO

Global emergence of Tigecycline resistant Acinetobacter baumannii (TRAB) is on the horizon and poses a very serious threat to human health. There is a pressing demand for suitable therapeutics against this pathogen, particularly a vaccine to protect against TRAB infections. We present a comprehensive investigation of the complete proteome of a TRAB AB031 strain to predict promiscuous antigenic, non-allergenic, virulent B-cell derived T-cell epitopes and formulate a multi-epitope vaccine against the pathogen. We identified epitopes from three proteins: outer membrane protein assembly factor (BamA), fimbrial biogenesis outer membrane usher protein (FimD) and type IV secretion protein (Rhs) that are appropriate for vaccine design. These proteins constitute the core proteome of the pathogen, are essential, localized at the pathogen surface, non-homologous to humans, mice and to the beneficial probiotic bacteria that reside the human gut. Moreover, these proteins are ideal candidates for experimental investigation as they have favorable physicochemical properties and have strong cellular interacting networks. The predicted epitopes: FPLNDKPGD (BamA), FVHAEEAAA (FimD) and YVVAGTAAA (Rhs) have exo-membrane topology for efficient recognition of the host immune system and high affinity for the most prevalent allele in human populations, the DRB*0101. These epitopes were linked and attached to an adjuvant to enhance its antigenicity. The multi-epitope vaccine-construct was docked with the TLR4 receptor to assess its affinity for the protein and thus its presentation to the host immune system. Docking results were validated through molecular dynamics simulations and binding free energies were calculated using the molecular mechanics/generalized Born (MM-GBSA) method. In conclusion, we expect the designed chimeric vaccine is highly likely to be effective against infections caused by TRAB.


Assuntos
Acinetobacter baumannii/efeitos dos fármacos , Antígenos de Bactérias/química , Proteínas da Membrana Bacteriana Externa/química , Vacinas Bacterianas/química , Biologia Computacional , Descoberta de Drogas/métodos , Epitopos/química , Acinetobacter baumannii/química , Acinetobacter baumannii/imunologia , Antibacterianos/farmacologia , Antígenos de Bactérias/imunologia , Proteínas da Membrana Bacteriana Externa/imunologia , Vacinas Bacterianas/imunologia , Farmacorresistência Bacteriana , Mapeamento de Epitopos , Epitopos/imunologia , Simulação de Acoplamento Molecular , Simulação de Dinâmica Molecular , Estrutura Secundária de Proteína , Estrutura Terciária de Proteína , Proteoma/química , Tigeciclina/farmacologia , Receptor 4 Toll-Like/química , Vacinas de Subunidades/química , Vacinas de Subunidades/imunologia
17.
Breast ; 44: 128-134, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30769238

RESUMO

The immune system plays a dual role of host-protecting and tumor-promoting, as elegantly expressed by the 'cancer immunoediting' hypothesis. Although breast cancer has not been traditionally considered to be immunogenic, recently there is accumulating and solid evidence on the association between immune system and breast cancer. To mount an effective anti-tumor response, host immunosurveillance must recognize tumor-specific epitopes, thus defining the antigenicity of a tumor. Neoantigens are mutant cancer peptides that arise as terminal products of the expression of somatic cancer mutations. Neoantigens and major histocompatibility complex (MHC) proteins present together to effector cells of the immune system. Neoantigen vaccines have shown promising results in inducing neoantigen-specific T-cell responses. Currently, cancer vaccines are under evaluation in breast cancer to avoid recurrences in patients at high risk despite optimal standard therapy. Given the promise of a very specific long-term antitumor immune response, the development of cancer vaccines continues is of great interest. Combinations of neoantigen vaccines and other immunotherapies are also studied to evade cancer immune escape.


Assuntos
Antígenos de Neoplasias/uso terapêutico , Neoplasias da Mama/terapia , Vacinas Anticâncer/uso terapêutico , Vacinas de Subunidades/uso terapêutico , Antígenos de Neoplasias/imunologia , Neoplasias da Mama/imunologia , Vacinas Anticâncer/imunologia , Feminino , Humanos , Imunoterapia/métodos , Medicina de Precisão/métodos , Vacinas de Subunidades/imunologia
18.
Microb Pathog ; 129: 206-212, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30772476

RESUMO

Streptococcus pneumoniae infection is associated with very high morbidity and mortality throughout the world. Vaccines are an effective measure for the reduction of S. pneumoniae infection. In particular, protein vaccines are attracting increasing attention because of their good immunogenicity and wide coverage of serotypes. Therefore, identifying effective protein vaccine targets is important for protein vaccine development. SP0148 is a promising protein vaccine target for S. pneumoniae and is capable of reducing S. pneumoniae colonization in the nasopharynx of mice through the IL-17A pathway. However, the protective effects of SP0148 in fatal pneumococcal infection have not been evaluated. This study used subcutaneous and nasal immunization routes to systematically evaluate the protective effects of the SP0148 protein in fatal pneumococcal infection. Subcutaneous and nasal mucosal immunization with recombinant SP0148 protein produced effective immune protection against infection with a lethal dose of S. pneumoniae and significantly prolonged survival time and increased the survival rate of mice. Furthermore, nasal immunization with SP0148 induced mouse splenocytes to secrete high levels of the cytokines IFN-γ and IL-17A. Both recombinant SP0148 protein and its antiserum inhibited the adhesion of S.pneumoniae D39 to A549 human lung epithelial cells in a dose-dependent manner. In summary, SP0148 induced mice to produce protective immune responses to fatal S. pneumoniae infection, and our results could contribute to the accumulating data on the use of SP0148 protein vaccines.


Assuntos
Antígenos de Bactérias/imunologia , Proteínas de Bactérias/imunologia , Vacinas Pneumocócicas/imunologia , Pneumonia Pneumocócica/prevenção & controle , Streptococcus pneumoniae/imunologia , Células A549 , Administração Intranasal , Animais , Anticorpos Antibacterianos/sangue , Antígenos de Bactérias/genética , Aderência Bacteriana , Proteínas de Bactérias/genética , Modelos Animais de Doenças , Células Epiteliais/microbiologia , Feminino , Humanos , Injeções Subcutâneas , Interferon gama/metabolismo , Interleucina-17/metabolismo , Leucócitos Mononucleares/imunologia , Camundongos Endogâmicos C57BL , Vacinas Pneumocócicas/administração & dosagem , Vacinas Pneumocócicas/genética , Streptococcus pneumoniae/fisiologia , Análise de Sobrevida , Vacinas de Subunidades/administração & dosagem , Vacinas de Subunidades/genética , Vacinas de Subunidades/imunologia , Vacinas Sintéticas/administração & dosagem , Vacinas Sintéticas/genética , Vacinas Sintéticas/imunologia
19.
Med Microbiol Immunol ; 208(2): 227-238, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30790057

RESUMO

Immunoinformatics has come by leaps and bounds to finding potent vaccine candidates against various pathogens. In the current study, a combination of different T (CD4+ and CD8+) and B cell epitope prediction tools was applied to find peptides containing multiple epitopes against Ebola nucleoprotein (NP) and the presentation of peptides to human leukocyte antigen (HLA) molecules was analyzed by prediction, docking and population coverage tools. Further, potential peptides were analyzed by ELISA for peptide induced IFN-γ secretion in peripheral blood mononuclear cells isolated from healthy volunteers. Six peptides were obtained after merging the overlapping multiple HLA I (CD8+) and II (CD4+) restricted T cell epitopes as well as B cell epitopes and eliminating the peptides liable to generate autoimmune and allergic response. All peptides displayed 100% conservancy in Zaire ebolavirus. In other Ebola virus species (Sudan, Bundibugyo and Taï forest) and Filoviridae members (Lloviuvirus and Margburgvirus), some peptides were found to be conserved with minor variations. Prediction tools confirmed the ability of predicted peptides to bind with diverse HLA (HLA-A, HLA-B, HLA-DP, HLA-DQ and HLA-DR) alleles. CABS-dock results displayed that the average root mean square deviation (RMSD) value was less than three in majority of cases representing strong binding affinity with HLA alleles. Population coverage analysis predicted high coverage (> 85%) for expected immune response in four continents (Africa, America, Asia and Europe). Nine out of ten blood samples exhibited enhanced IFN-γ secretion for two peptides (P2 and P3). Thus, the identified NP peptides can be considered as potential synthetic vaccine candidates against Ebola virus.


Assuntos
Vacinas contra Ebola/imunologia , Ebolavirus/imunologia , Epitopos/imunologia , Antígenos HLA/metabolismo , Doença pelo Vírus Ebola/prevenção & controle , Leucócitos Mononucleares/imunologia , Nucleoproteínas/imunologia , Antígenos Virais/genética , Antígenos Virais/imunologia , Biologia Computacional , Vacinas contra Ebola/genética , Ebolavirus/genética , Epitopos/genética , Antígenos HLA/genética , Voluntários Saudáveis , Humanos , Interferon gama/metabolismo , Nucleoproteínas/genética , Vacinas de Subunidades/genética , Vacinas de Subunidades/imunologia
20.
Viruses ; 11(2)2019 02 03.
Artigo em Inglês | MEDLINE | ID: mdl-30717485

RESUMO

For the development of an effective HIV-1 vaccine, evolutionarily conserved epitopes between feline and human immunodeficiency viruses (FIV and HIV-1) were determined by analyzing overlapping peptides from retroviral genomes that induced both anti-FIV/HIV T cell-immunity in the peripheral blood mononuclear cells from the FIV-vaccinated cats and the HIV-infected humans. The conserved T-cell epitopes on p24 and reverse transcriptase were selected based on their robust FIV/HIV-specific CD8⁺ cytotoxic T lymphocyte (CTL), CD4⁺ CTL, and polyfunctional T-cell activities. Four such evolutionarily conserved epitopes were formulated into four multiple antigen peptides (MAPs), mixed with an adjuvant, to be tested as FIV vaccine in cats. The immunogenicity and protective efficacy were evaluated against a pathogenic FIV. More MAP/peptide-specific CD4⁺ than CD8⁺ T-cell responses were initially observed. By post-third vaccination, half of the MAP/peptide-specific CD8⁺ T-cell responses were higher or equivalent to those of CD4⁺ T-cell responses. Upon challenge, 15/19 (78.9%) vaccinated cats were protected, whereas 6/16 (37.5%) control cats remained uninfected, resulting in a protection rate of 66.3% preventable fraction (p = 0.0180). Thus, the selection method used to identify the protective FIV peptides should be useful in identifying protective HIV-1 peptides needed for a highly protective HIV-1 vaccine in humans.


Assuntos
Epitopos de Linfócito T/imunologia , Síndrome de Imunodeficiência Adquirida Felina/prevenção & controle , Imunogenicidade da Vacina , Peptídeos/imunologia , Vacinas Virais/imunologia , Animais , Anticorpos Antivirais/sangue , Linfócitos T CD4-Positivos/imunologia , Gatos , Reações Cruzadas , Síndrome de Imunodeficiência Adquirida Felina/imunologia , Infecções por HIV/imunologia , Infecções por HIV/prevenção & controle , HIV-1 , Humanos , Imunidade Celular , Vírus da Imunodeficiência Felina , Ativação Linfocitária , Organismos Livres de Patógenos Específicos , Vacinação/veterinária , Vacinas de Subunidades/imunologia
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