Your browser doesn't support javascript.
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 12.189
Filtrar
1.
JAMA ; 322(2): 123-133, 2019 07 09.
Artigo em Inglês | MEDLINE | ID: mdl-31287523

RESUMO

Importance: Herpes zoster, a frequent complication following autologous hematopoietic stem cell transplantation (HSCT), is associated with significant morbidity. A nonlive adjuvanted recombinant zoster vaccine has been developed to prevent posttransplantation zoster. Objective: To assess the efficacy and adverse event profile of the recombinant zoster vaccine in immunocompromised autologous HSCT recipients. Design, Setting, and Participants: Phase 3, randomized, observer-blinded study conducted in 167 centers in 28 countries between July 13, 2012, and February 1, 2017, among 1846 patients aged 18 years or older who had undergone recent autologous HSCT. Interventions: Participants were randomized to receive 2 doses of either recombinant zoster vaccine (n = 922) or placebo (n = 924) administered into the deltoid muscle; the first dose was given 50 to 70 days after transplantation and the second dose 1 to 2 months thereafter. Main Outcomes and Measures: The primary end point was occurrence of confirmed herpes zoster cases. Results: Among 1846 autologous HSCT recipients (mean age, 55 years; 688 [37%] women) who received 1 vaccine or placebo dose, 1735 (94%) received a second dose and 1366 (74%) completed the study. During the 21-month median follow-up, at least 1 herpes zoster episode was confirmed in 49 vaccine and 135 placebo recipients (incidence, 30 and 94 per 1000 person-years, respectively), an incidence rate ratio (IRR) of 0.32 (95% CI, 0.22-0.44; P < .001), equivalent to 68.2% vaccine efficacy. Of 8 secondary end points, 3 showed significant reductions in incidence of postherpetic neuralgia (vaccine, n=1; placebo, n=9; IRR, 0.1; 95% CI, 0.00-0.78; P = .02) and of other prespecified herpes zoster-related complications (vaccine, n=3; placebo, n=13; IRR, 0.22; 95% CI, 0.04-0.81; P = .02) and in duration of severe worst herpes zoster-associated pain (vaccine, 892.0 days; placebo, 6275.0 days; hazard ratio, 0.62; 95% CI, 0.42-0.89; P = .01). Five secondary objectives were descriptive. Injection site reactions were recorded in 86% of vaccine and 10% of placebo recipients, of which pain was the most common, occurring in 84% of vaccine recipients (grade 3: 11%). Unsolicited and serious adverse events, potentially immune-mediated diseases, and underlying disease relapses were similar between groups at all time points. Conclusions and Relevance: Among adults who had undergone autologous HSCT, a 2-dose course of recombinant zoster vaccine compared with placebo significantly reduced the incidence of herpes zoster over a median follow-up of 21 months. Trial Registration: ClinicalTrials.gov Identifier: NCT01610414.


Assuntos
Transplante de Células-Tronco Hematopoéticas , Vacina contra Herpes Zoster , Herpes Zoster/prevenção & controle , Hospedeiro Imunocomprometido , Adjuvantes Imunológicos , Adulto , Feminino , Seguimentos , Herpes Zoster/epidemiologia , Vacina contra Herpes Zoster/administração & dosagem , Hospitalização/estatística & dados numéricos , Humanos , Incidência , Injeções Intramusculares , Masculino , Pessoa de Meia-Idade , Neuralgia Pós-Herpética/prevenção & controle , Modelos de Riscos Proporcionais , Método Simples-Cego , Transplante Autólogo , Vacinas Sintéticas/administração & dosagem
2.
J Zoo Wildl Med ; 50(2): 337-341, 2019 Jun 13.
Artigo em Inglês | MEDLINE | ID: mdl-31260198

RESUMO

Canine distemper virus (CDV) vaccination using commercial vaccines has been recommended as a useful preventive tool in zoological collections worldwide for the past 30 yr. Zoological facilities have not conducted studies to assess the effectiveness and safety of the multivalent Recombitek C6 and C8 in nondomestic carnivores. They are the only CDV recombinant vaccines available in Latin America. Seventeen clinically healthy red foxes born in Buin Zoo were divided into three groups and administered 1 ml of Recombitek C6 vaccine. Group A consisted of three animals of 9 mo of age without previous vaccination (WPV) that received a single dose. Group B consisted of four animals of 10 mo of age WPV; they received a series of three doses with a 21-day interval between doses. Group C consisted of eight animals > 1 yr of age that had received a previous vaccination > 1 yr ago; they received a single-dose booster vaccination. Titers for antibodies against CDV were measured by a serum neutralization test. All animals remained clinically healthy throughout the study period and without clinical signs of disease. Only two foxes (group C) did not show any increase in the antibody titer to the vaccine. All animals of groups A and B seroconverted at 21 days after the first vaccination. Only two animals (both from group B) showed an adequate antibody protective response (titers >100) after 180 days. Absence of adverse reactions in red foxes included in this study supports the safety and apparently nondeleterious effect of CDV recombinant vaccine reported in other nondomestic carnivores. Low antibody response and lack of persistence in the serological response 6 mo after vaccination with a single dose suggested limited protective benefits in this species. Additional research is needed to confirm the antibody titer response to multiple vaccinations in this species.


Assuntos
Vírus da Cinomose Canina , Raposas/imunologia , Vacinas Virais/imunologia , Animais , Animais de Zoológico , Anticorpos Antivirais/sangue , Cinomose/prevenção & controle , Raposas/sangue , Esquemas de Imunização , Imunização Secundária , Vacinação/veterinária , Vacinas Sintéticas
3.
J Zoo Wildl Med ; 50(2): 478-481, 2019 Jun 13.
Artigo em Inglês | MEDLINE | ID: mdl-31260219

RESUMO

Red pandas (Ailurus fulgens) are susceptible to canine distemper, with a number of reported vaccine-induced canine distemper cases. Canarypox-vectored recombinant canine distemper vaccines (PureVax Ferret Distemper [PFD] and Recombitek CDV [rCDV]) provide protection without inoculating a live distemper virus, but there are currently no published data regarding these vaccines' safety and efficacy in red pandas. One hundred twenty-two serum samples were collected from 50 captive red pandas and analyzed for antibodies to canine distemper. All naïve red pandas (n = 20) had negative titers. Naïve pandas receiving two PFD vaccinations had either negative or intermediate titers (n = 4). In contrast, naïve pandas receiving a series of two or three rCDV vaccinations (n = 14) had greater antibody responses. Red pandas vaccinated with PFD >12 mo since their last vaccination and a rCDV booster vaccination showed the highest titers observed. We recommend red pandas be administered a series of at least three recombinant vaccine (PDF or rDCV) vaccinations, followed by annual booster vaccinations.


Assuntos
Ailuridae/sangue , Anticorpos Antivirais/sangue , Vírus da Cinomose Canina/imunologia , Cinomose/prevenção & controle , Vacinas Virais/imunologia , Animais , Cinomose/virologia , Vetores Genéticos , Imunização Secundária , Vacinação , Vacinas Sintéticas/imunologia
4.
Vet Parasitol ; 271: 45-50, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31303202

RESUMO

Cryptosporidium parvum is a protozoan parasite of the phylum Apicomplexa responsible for cryptosporidiosis in calves, a disease that causes significant diarrhea and impairs gain of body weight, generating important production losses. As to now, no effective drugs or vaccines are available for the treatment or prevention of bovine cryptosporidiosis. Several reports suggest that development of a vaccine to prevent cryptosporidiosis is feasible, but relatively few vaccine candidates have been characterized and tested. The most prominent C. parvum antigen is gp60, an O-glycosylated mucin-like protein tethered to the parasite membrane by a glycosylphosphatidylinositol (GPI) anchor. Gp60 has been shown to be involved in essential mechanisms for the survival of C. parvum, such as recognition, adhesion to, and invasion of host cells. This work was aimed at expressing gp60 in Tetrahymena thermophila, a ciliated protozoon with numerous advantages for the heterologous expression of eukaryotic proteins, as a first approach for the development of a recombinant vaccine for bovine cryptosporidiosis. T. thermophila-expressed gp60 localized to the protozoon cell surface and oral apparatus, and partitioned into the Triton X-114 detergent phase. This indicates that the protein entered the reticuloendothelial system of the ciliate, and suggests it contains a GPI-anchor. Homogenates of gp60-expressing T. thermophila cells were recognized by sera from calves naturally infected with C. parvum demonstrating their immunoreactivity. In summary, the heterologous expression of gp60, a C. parvum-encoded GPI-anchored protein, has been successfully demonstrated in the ciliate T. thermophila.


Assuntos
Antígenos de Protozoários/genética , Antígenos de Protozoários/imunologia , Glicoproteínas/genética , Glicoproteínas/imunologia , Tetrahymena thermophila/genética , Animais , Bovinos , Doenças dos Bovinos/imunologia , Doenças dos Bovinos/prevenção & controle , Criptosporidiose/imunologia , Criptosporidiose/prevenção & controle , Cryptosporidium parvum/genética , Vacinas Sintéticas/sangue , Vacinas Sintéticas/genética
5.
APMIS ; 127(10): 671-680, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31344276

RESUMO

Regardless of the communal impact of Shiga toxins, till today neither a specific treatment nor licensed vaccine is available. Lactococcus lactis (L. lactis), generally regarded as safe organism, is well known to provide a valuable approach regarding the oral delivery of vaccines. This study was undertaken to evaluate the protective efficacy of Stx2a1 expressed in nisin-inducible L. lactis, against Shiga toxins (Stx1, Stx2) in mouse model. Oral immunization of BALB/c mice with LL-Stx2a1 elicited significant serum antibody titer with elevated fecal and serum IgA, along with minimized intestinal and kidney damage resulting in survival of immunized animals at 84% and 100% when challenged with 10 × LD50 of Escherichia coli O157 and Shigella dysenteriae toxins, respectively. HeLa cells incubated with immune sera and toxin mixture revealed high neutralizing capacity with 90% cell survivability against both the toxins. Mice immunized passively with both toxins and antibody mixture survived the observation period of 15 days, and the controls administered with sham sera and toxins were succumbed to death within 3 days. Our results revealed protective efficacy and toxin neutralization ability of LL-Stx2a1, proposing it as an oral vaccine candidate against Shiga toxicity mediated by E. coli O157 and S. dysenteriae.


Assuntos
Vacinas Bacterianas/administração & dosagem , Vacinas Bacterianas/imunologia , Escherichia coli O157/imunologia , Envenenamento/prevenção & controle , Toxina Shiga/imunologia , Toxina Shiga/toxicidade , Shigella dysenteriae/imunologia , Administração Oral , Animais , Anticorpos Antibacterianos/administração & dosagem , Anticorpos Antibacterianos/sangue , Anticorpos Neutralizantes/administração & dosagem , Anticorpos Neutralizantes/sangue , Antitoxinas/administração & dosagem , Antitoxinas/sangue , Vacinas Bacterianas/genética , Sobrevivência Celular/efeitos dos fármacos , Modelos Animais de Doenças , Portadores de Fármacos/administração & dosagem , Escherichia coli O157/genética , Vetores Genéticos/administração & dosagem , Células HeLa , Humanos , Lactococcus lactis/genética , Camundongos , Camundongos Endogâmicos BALB C , Toxina Shiga/genética , Shigella dysenteriae/genética , Análise de Sobrevida , Resultado do Tratamento , Vacinas Sintéticas/administração & dosagem , Vacinas Sintéticas/genética , Vacinas Sintéticas/imunologia
6.
Parasit Vectors ; 12(1): 347, 2019 Jul 12.
Artigo em Inglês | MEDLINE | ID: mdl-31300007

RESUMO

BACKGROUND: Live anticoccidial vaccines have been a tremendous success for disease prevention. The establishment of the reverse genetic manipulation platform has enabled the development of Eimeria parasites, the live anticoccidial vaccine strains, as vaccine vectors. In our previous study, recombinant E. tenella expressing a single immunodominant antigen of E. maxima (Et-EmIMP1) was able to protect chickens against challenge infection with E. maxima. This promising result encouraged us to further explore strategies to improve the protection efficacy of recombinant Eimeria and develop it as a vaccine vector. RESULTS: We constructed a novel recombinant Eimeria line expressing apical membrane antigen 1 of E. maxima (Et-EmAMA1) and then immunized chickens with Et-EmAMA1 and/or Et-EmIMP1. We found that the E. maxima soluble antigen-specific cell-mediated immunity was much stronger in the birds that were co-immunized with Et-EmAMA1 and Et-EmIMP1 than in those that were immunized with Et-EmAMA1 or Et-EmIMP1 alone. The oocyst production after E. maxima infection was significantly reduced in the recombinant Eimeria-immunized birds compared with the wild-type-immunized and naïve birds. The oocyst production in the birds co-immunized with Et-EmAMA1 and Et-EmIMP1 was consistently the lowest among the treatment groups after E. maxima infection. CONCLUSIONS: These results demonstrated that Eimeria is an effective vaccine vector that can carry and deliver heterologous Eimeria antigens to the host immune system and trigger specific immune responses. Our results also suggested that increasing the number of recombinant Eimeria lines is an effective approach to enhance protective immunity against infections with heterologous pathogens.


Assuntos
Coccidiose/veterinária , Eimeria tenella/genética , Eimeria/genética , Imunidade Celular , Doenças das Aves Domésticas/prevenção & controle , Vacinas Protozoárias/imunologia , Animais , Antígenos de Protozoários/imunologia , Galinhas , Coccidiose/prevenção & controle , Eimeria/imunologia , Eimeria tenella/imunologia , Doenças das Aves Domésticas/imunologia , Organismos Livres de Patógenos Específicos , Vacinas Atenuadas , Vacinas Sintéticas
7.
BMC Infect Dis ; 19(1): 482, 2019 May 30.
Artigo em Inglês | MEDLINE | ID: mdl-31146699

RESUMO

BACKGROUND: To assess the immune persistence conferred by a Chinese hamster ovary (CHO)-derived hepatitis B vaccine (HepB) 17 to 20 years after primary immunization during early life. METHODS: Participants born between 1997 and 1999 who received a full course of primary vaccination with HepB (CHO) and who had no experience with booster vaccination were enrolled. Blood samples were required from each participant for measurement of hepatitis B surface antibody (anti-HBs), surface antigen and core antibody levels. For those who possessed an anti-HBs antibody < 10 mIU/mL, a single dose of HepB was administered, and 30 days later, serum specimens were collected to assess the booster effects. RESULTS: A total of 1352 participants were included in this study. Of these, 1007 (74.5%) participants could retain an anti-HBs antibody ≥10 mIU/mL, with a geometric mean concentration (GMC) of 57.4 mIU/mL. HBsAg was detected in six participants, resulting in a HBsAg carrier rate of 0.4% (6/1352). Of those participants with anti-HBs antibodies < 10 mIU/mL, after a challenge dose, 231 (93.1%) presented an anti-HBs antibody ≥10 mIU/mL, with a GMC of 368.7 mIU/mL. A significant increase in the anti-HBs positive rate (≥ 10 mIU/mL) after challenge was observed in participants with anti-HBs antibodies between 2.5 and 10 mIU/mL and participants boosted with HepB (CHO), rather than those with anti-HBs antibodies < 2.5 mIU/mL and those boosted with HepB (SC). CONCLUSION: Since satisfactory immune protection against HBV infection conferred by primary vaccination administered 17-20 years ago was demonstrated, there is currently no urgent need for booster immunization.


Assuntos
Anticorpos Anti-Hepatite B/sangue , Vacinas contra Hepatite B/administração & dosagem , Hepatite B/prevenção & controle , Imunização Secundária , Prevenção Primária , Vacinas Sintéticas/imunologia , Vacinas Sintéticas/uso terapêutico , Adolescente , Adulto , Animais , Células CHO , Cricetinae , Cricetulus , Feminino , Seguimentos , Hepatite B/imunologia , Antígenos de Superfície da Hepatite B/imunologia , Vacinas contra Hepatite B/imunologia , Humanos , Recém-Nascido , Masculino , Prevenção Primária/métodos , Estudos Retrospectivos , Fatores de Tempo , Adulto Jovem
8.
Nat Commun ; 10(1): 2688, 2019 06 19.
Artigo em Inglês | MEDLINE | ID: mdl-31217437

RESUMO

Neoantigens (nAgs) are promising tumor antigens for cancer vaccination with the potential of inducing robust and selective T cell responses. Genetic vaccines based on Adenoviruses derived from non-human Great Apes (GAd) elicit strong and effective T cell-mediated immunity in humans. Here, we investigate for the first time the potency and efficacy of a novel GAd encoding multiple neoantigens. Prophylactic or early therapeutic vaccination with GAd efficiently control tumor growth in mice. In contrast, combination of the vaccine with checkpoint inhibitors is required to eradicate large tumors. Gene expression profile of tumors in regression shows abundance of activated tumor infiltrating T cells with a more diversified TCR repertoire in animals treated with GAd and anti-PD1 compared to anti-PD1. Data suggest that effectiveness of vaccination in the presence of high tumor burden correlates with the breadth of nAgs-specific T cells and requires concomitant reversal of tumor suppression by checkpoint blockade.


Assuntos
Adenoviridae/imunologia , Antineoplásicos Imunológicos/uso terapêutico , Vacinas Anticâncer/uso terapêutico , Neoplasias/terapia , Vacinas Virais/uso terapêutico , Adenoviridae/genética , Animais , Antígenos de Neoplasias/imunologia , Antineoplásicos Imunológicos/farmacologia , Vacinas Anticâncer/genética , Vacinas Anticâncer/imunologia , Linhagem Celular Tumoral/transplante , Terapia Combinada/métodos , Modelos Animais de Doenças , Feminino , Humanos , Imunoterapia/métodos , Ativação Linfocitária/efeitos dos fármacos , Ativação Linfocitária/imunologia , Linfócitos do Interstício Tumoral/efeitos dos fármacos , Linfócitos do Interstício Tumoral/imunologia , Camundongos , Neoplasias/imunologia , Receptor de Morte Celular Programada 1/antagonistas & inibidores , Receptor de Morte Celular Programada 1/imunologia , Linfócitos T/efeitos dos fármacos , Linfócitos T/imunologia , Resultado do Tratamento , Carga Tumoral/efeitos dos fármacos , Carga Tumoral/imunologia , Vacinas Sintéticas/genética , Vacinas Sintéticas/imunologia , Vacinas Sintéticas/uso terapêutico , Vacinas Virais/genética , Vacinas Virais/imunologia
9.
Vet Microbiol ; 234: 77-82, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31213275

RESUMO

Control of currently circulating re-assorted low-pathogenicity avian influenza (LPAI) H9N2 is a major concern for both animal and human health. Thus, an improved LPAI H9N2 vaccination strategy is needed to induce complete immunity in chickens against LPAI H9N2 virus strains. Cytokines play a crucial role in mounting both the type and extent of an immune response generated following infection with a pathogen or after vaccination. To improve the efficacy of inactivated LPAI H9N2 vaccine, prokaryotic expression recombination chicken interferon-α (rchIFN-α) was used as vaccine adjuvant.In this study chIFN-α was used as adjuvant in inactivated AI H9N2 vaccine, modulated the immune response of chickens against the vaccine antigen through enhanced humoral and Th1-biased cell-mediated immunity, compared to chickens that received single AI H9N2 vaccine. To further test the protective efficacy of this improved vaccination regimen, immunized chickens were challenged with a high dose of LPAI H9N2 virus. Combined administration rchIFN-α showed markedly enhanced protection compared to single administration of the vaccine, as determined by mortality, clinical severity, and feed and water intake. This enhancement of protective immunity was further confirmed by reduced rectal shedding and replication of AIV H9N2 in challenged chickens. Our results indicate the value of combined administration of rchIFN-α to generate an effective immunization strategy in chickens against LPAI H9N2.


Assuntos
Imunogenicidade da Vacina , Vacinas contra Influenza/imunologia , Influenza Aviária/prevenção & controle , Interferon-alfa/genética , Adjuvantes Imunológicos , Animais , Anticorpos Antivirais/sangue , Galinhas , Imunidade Celular , Imunidade Humoral , Vírus da Influenza A Subtipo H9N2/imunologia , Vacinas contra Influenza/genética , Influenza Aviária/imunologia , Interferon-alfa/imunologia , Organismos Livres de Patógenos Específicos , Vacinas de Produtos Inativados/genética , Vacinas de Produtos Inativados/imunologia , Vacinas Sintéticas/administração & dosagem , Vacinas Sintéticas/imunologia , Eliminação de Partículas Virais
10.
J Vet Sci ; 20(3): e30, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-31161748

RESUMO

Gonadotropin-releasing hormone (GnRH) is secreted from the hypothalamus and anti-GnRH antibodies are not formed under normal conditions. However, administration an excess of recombinant GnRH protein results in the formation of anti-GnRH. We evaluated the efficacy of the recombinant Salmonella typhimurium flagellin fljB (STF2)-GnRH vaccine in inducing infertility in 17 intact male cats. The first vaccination and a boosting vaccine was injected for examination. Serum was obtained from blood collected at monthly intervals and anti-GnRH antibodies and testosterone concentrations were determined. Six months after the vaccination, testicular samples are obtained and used for histological examination. Compared with sham control group, the injection groups showed an increase in anti-GnRH antibody titers and testosterone concentrations tended to be reduced in the injection groups and increased in the control group. Histological evaluations and Johnsen's testicular biopsy scores revealed testicular hypoplasia in the 2 injection groups. Consequently, normal sexual maturation with sperm production was observed in the control group. In contrast, the cats that received the GnRH vaccine showed weak (2 of 7 cats) or moderate (4 out of 7 cats) dose-dependent infertility effects. On the basis of the results, the STF2-GnRH vaccine was identified to be effective in inducing infertility in male cats. The results of this study thus indicate the possibility of immunological castration targeting feral cats.


Assuntos
Flagelina/imunologia , Hormônio Liberador de Gonadotropina/imunologia , Infertilidade Masculina/induzido quimicamente , Orquiectomia/veterinária , Maturidade Sexual/efeitos dos fármacos , Espermatogênese/efeitos dos fármacos , Vacinas Anticoncepcionais/normas , Animais , Anticorpos/sangue , Gatos , Escherichia coli/genética , Flagelina/genética , Hormônio Liberador de Gonadotropina/genética , Masculino , Orquiectomia/métodos , Proteínas Recombinantes/farmacologia , Testículo/efeitos dos fármacos , Testosterona/sangue , Vacinas Anticoncepcionais/farmacologia , Vacinas Sintéticas/imunologia , Vacinas Sintéticas/farmacologia
11.
Emerg Microbes Infect ; 8(1): 760-772, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31130102

RESUMO

The recently identified Middle East Respiratory Syndrome Coronavirus (MERS-CoV) causes severe and fatal acute respiratory illness in humans. However, no approved prophylactic and therapeutic interventions are currently available. The MERS-CoV envelope spike protein serves as a crucial target for neutralizing antibodies and vaccine development, as it plays a critical role in mediating viral entry through interactions with the cellular receptor, dipeptidyl peptidase 4 (DPP4). Here, we constructed a recombinant rare serotype of the chimpanzee adenovirus 68 (AdC68) that expresses full-length MERS-CoV S protein (AdC68-S). Single intranasal immunization with AdC68-S induced robust and sustained neutralizing antibody and T cell responses in BALB/c mice. In a human DPP4 knock-in (hDPP4-KI) mouse model, it completely protected against lethal challenge with a mouse-adapted MERS-CoV (MERS-CoV-MA). Passive transfer of immune sera to naïve hDPP4-KI mice also provided survival advantages from lethal MERS-CoV-MA challenge. Analysis of sera absorption and isolated monoclonal antibodies from immunized mice demonstrated that the potent and broad neutralizing activity was largely attributed to antibodies targeting the receptor binding domain (RBD) of the S protein. These results show that AdC68-S can induce protective immune responses in mice and represent a promising candidate for further development against MERS-CoV infection in both dromedaries and humans.


Assuntos
Infecções por Coronavirus/prevenção & controle , Portadores de Fármacos/administração & dosagem , Coronavírus da Síndrome Respiratória do Oriente Médio/imunologia , Glicoproteína da Espícula de Coronavírus/imunologia , Vacinas Virais/imunologia , Adenoviridae/genética , Administração Intranasal , Animais , Animais Geneticamente Modificados , Anticorpos Neutralizantes/sangue , Anticorpos Antivirais/sangue , Humanos , Imunização Passiva , Camundongos Endogâmicos BALB C , Coronavírus da Síndrome Respiratória do Oriente Médio/genética , Glicoproteína da Espícula de Coronavírus/genética , Análise de Sobrevida , Linfócitos T/imunologia , Resultado do Tratamento , Vacinas Sintéticas/administração & dosagem , Vacinas Sintéticas/genética , Vacinas Sintéticas/imunologia , Vacinas Virais/administração & dosagem , Vacinas Virais/genética
12.
Cancer Immunol Immunother ; 68(7): 1211-1222, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31069460

RESUMO

Human tumor cells express antigens that serve as targets for the host cellular immune system. This phase 1 dose-escalating study was conducted to assess safety and tolerability of G305, a recombinant NY-ESO-1 protein vaccine mixed with glucopyranosyl lipid A (GLA), a synthetic TLR4 agonist adjuvant, in a stable emulsion (SE). Twelve patients with solid tumors expressing NY-ESO-1 were treated using a 3 + 3 design. The NY-ESO-1 dose was fixed at 250 µg, while GLA-SE was increased from 2 to 10 µg. Safety, immunogenicity, and clinical responses were assessed prior to, during, and at the end of therapy. G305 was safe and immunogenic at all doses. All related AEs were Grade 1 or 2, with injection site soreness as the most commonly reported event (100%). Overall, 75% of patients developed antibody response to NY-ESO-1, including six patients with increased antibody titer ( ≥ 4-fold rise) and three patients with seroconversion from negative (titer < 100) to positive (titer ≥ 100). CD4 T-cell responses were observed in 44.4% of patients; 33.3% were new responses and 1 was boosted ( ≥ 2-fold rise). Following treatment, 8 of 12 patients had stable disease for 3 months or more; at the end of 1 year, three patients had stable disease and nine patients were alive. G305 is a potent immunotherapeutic agent that can stimulate NY-ESO-1-specific antibody and T-cell responses. The vaccine was safe at all doses of GLA-SE (2-10 µg) and showed potential clinical benefit in this population of patients.


Assuntos
Adjuvantes Imunológicos/administração & dosagem , Antígenos de Neoplasias/administração & dosagem , Vacinas Anticâncer/administração & dosagem , Glucosídeos/administração & dosagem , Lipídeo A/administração & dosagem , Proteínas de Membrana/administração & dosagem , Neoplasias/terapia , Adjuvantes Imunológicos/efeitos adversos , Adulto , Idoso , Antígenos de Neoplasias/efeitos adversos , Antígenos de Neoplasias/imunologia , Linfócitos T CD4-Positivos/efeitos dos fármacos , Linfócitos T CD4-Positivos/imunologia , Vacinas Anticâncer/efeitos adversos , Vacinas Anticâncer/imunologia , Drogas em Investigação/administração & dosagem , Drogas em Investigação/efeitos adversos , Feminino , Glucosídeos/efeitos adversos , Glucosídeos/imunologia , Humanos , Imunogenicidade da Vacina , Injeções Intramusculares , Lipídeo A/efeitos adversos , Lipídeo A/imunologia , Masculino , Proteínas de Membrana/efeitos adversos , Proteínas de Membrana/imunologia , Pessoa de Meia-Idade , Neoplasias/imunologia , Neoplasias/patologia , Proteínas Recombinantes/administração & dosagem , Proteínas Recombinantes/efeitos adversos , Proteínas Recombinantes/imunologia , Receptor 4 Toll-Like/agonistas , Receptor 4 Toll-Like/imunologia , Resultado do Tratamento , Vacinas Sintéticas/administração & dosagem , Vacinas Sintéticas/efeitos adversos , Vacinas Sintéticas/imunologia , Adulto Jovem
13.
Nat Commun ; 10(1): 2214, 2019 05 17.
Artigo em Inglês | MEDLINE | ID: mdl-31101810

RESUMO

CD8+ T cells provide a critical defence from pathogens at mucosal epithelia including the female reproductive tract (FRT). Mucosal immunisation is considered essential to initiate this response, however this is difficult to reconcile with evidence that antigen delivered to skin can recruit protective CD8+ T cells to mucosal tissues. Here we dissect the underlying mechanism. We show that adenovirus serotype 5 (Ad5) bio-distributes at very low level to non-lymphoid tissues after skin immunisation. This drives the expansion and activation of CD3- NK1.1+ group 1 innate lymphoid cells (ILC1) within the FRT, essential for recruitment of CD8+ T-cell effectors. Interferon gamma produced by activated ILC1 is critical to licence CD11b+Ly6C+ monocyte production of CXCL9, a chemokine required to recruit skin primed CXCR3+ CD8+T-cells to the FRT. Our findings reveal a novel role for ILC1 to recruit effector CD8+ T-cells to prevent virus spread and establish immune surveillance at barrier tissues.


Assuntos
Linfócitos T CD8-Positivos/imunologia , Genitália Feminina/imunologia , Pele/imunologia , Vacinas Virais/administração & dosagem , Viroses/prevenção & controle , Adenovírus Humanos/genética , Adenovírus Humanos/imunologia , Administração Cutânea , Animais , Quimiocina CXCL9 , Modelos Animais de Doenças , Feminino , Genitália Feminina/citologia , Genitália Feminina/virologia , Células HEK293 , Interações Hospedeiro-Patógeno/imunologia , Humanos , Imunidade Inata , Camundongos , Camundongos Endogâmicos C57BL , Monócitos/imunologia , Membrana Mucosa/citologia , Membrana Mucosa/imunologia , Membrana Mucosa/virologia , Receptores CXCR3 , Pele/citologia , Pele/virologia , Resultado do Tratamento , Vacinação/métodos , Vacinas Sintéticas/administração & dosagem , Vacinas Sintéticas/genética , Vacinas Sintéticas/imunologia , Vacinas Virais/genética , Vacinas Virais/imunologia , Viroses/imunologia , Viroses/virologia , Produtos do Gene gag do Vírus da Imunodeficiência Humana/genética , Produtos do Gene gag do Vírus da Imunodeficiência Humana/imunologia
14.
Microb Pathog ; 133: 103559, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31132417

RESUMO

Aeromonas salmonicida, the oldest known fish pathogen and currently endemic throughout most of the world in both fresh and marine waters, causes severe economic losses to the salmon farming industry. Although there have been many studies on the prevention of furunculosis over the past few decades, it is still prevalent in many fisheries. In this study, a recombinant adenovirus vaccine candidate harboring the highly immunogenic Vapa gene (pAd-easy-cmv-Vapa) was successfully constructed and tested. The immune protection rate and specific antibody levels in the peripheral blood were then determined after immunizing rainbow trout. In addition, relative levels of IgM and IgT in the head kidney and hindgut before and after immunization were measured by quantitative reverse transcription PCR. Western blotting results indicated that the recombinant adenovirus could infect HEK-293 cells and express the A layer protein (encoded by Vapa). Further, survival analysis of fish 28 days after challenge showed that immunization significantly lowered the mortality rate (40%) compared to that in the control group (76.6%) and empty vector group (73.6%). This also led to an increase in specific antibodies in peripheral serum. In addition, levels of IgM and IgT in the head kidney and hindgut were increased to varying degrees. In conclusion, our research provides a candidate vaccine for the prevention of Aeromonas salmonicida A450 infection in rainbow trout and lays the foundation for future research on adaptive immune mechanisms associated with rainbow trout antibodies.


Assuntos
Adenoviridae/genética , Aeromonas salmonicida/imunologia , Doenças dos Peixes/prevenção & controle , Infecções por Bactérias Gram-Negativas/imunologia , Infecções por Bactérias Gram-Negativas/veterinária , Imunização , Vacinas Sintéticas/imunologia , Imunidade Adaptativa , Vacinas contra Adenovirus , Aeromonas salmonicida/genética , Sequência de Aminoácidos , Animais , Anticorpos , Antígenos de Bactérias/genética , Antígenos de Bactérias/imunologia , Vacinas Bacterianas/genética , Vacinas Bacterianas/imunologia , Doenças dos Peixes/imunologia , Doenças dos Peixes/microbiologia , Infecções por Bactérias Gram-Negativas/microbiologia , Células HEK293 , Interações Hospedeiro-Patógeno , Humanos , Imunoglobulina M , Rim/imunologia , Oncorhynchus mykiss , Vacinação , Vacinas Sintéticas/genética
15.
Malar J ; 18(1): 186, 2019 May 29.
Artigo em Inglês | MEDLINE | ID: mdl-31142328

RESUMO

BACKGROUND: Whole parasite vaccination is an efficacious strategy to induce sterile immunity and to prevent malaria transmission. Understanding the mechanism and response of immune cells to vaccines plays a critical role in deciphering correlates of protection against infection and disease. Immunoassays, such as ELISpot, are commonly used to assess the immunogenicity of vaccines towards T cells and B cells. To date, these assays only analyse responses to specific antigens since they are based on recombinant parasite-derived proteins or peptides. There is the need for an agnostic approach that allows the evaluation of all sporozoite-associated antigens. METHODS: ELISpot plates coated with a defined amount of lysed Plasmodium falciparum sporozoites were used to assess the frequency of sporozoite-specific B cells in peripheral blood mononuclear cells from donors immunized with either a recombinant malaria vaccine or irradiated sporozoites. RESULTS: This report describes the assay conditions for a specific and sensitive sporozoite-based B cell ELISpot assay. The assay development considers the quality of sporozoite preparation as well as the detection threshold of the frequency of antigen-specific B cells. The assay enables the detection of sporozoite-specific IgM and IgG-producing B cells. Moreover, the assay can detect sporozoite-reactive B cells from subjects that were either vaccinated with the radiation attenuated sporozoite vaccine or a recombinant pre-erythrocytic vaccine. CONCLUSION: The newly developed sporozoite-based B cell ELISpot enables the monitoring of changes in the frequency of sporozoite-specific B cells. Applying this assay to assess the potency of vaccination regimens or seasonal changes in B cell populations from subjects residing in malaria-endemic areas will provide an opportunity to gain insight into immune mechanisms involved in protection and/or disease.


Assuntos
Linfócitos B/imunologia , ELISPOT , Vacinas Antimaláricas/imunologia , Esporozoítos/imunologia , Esporozoítos/efeitos da radiação , Anticorpos Antiprotozoários/sangue , Antígenos de Protozoários/imunologia , Ensaios Clínicos como Assunto , Humanos , Leucócitos Mononucleares/imunologia , Vacinas Antimaláricas/administração & dosagem , Malária Falciparum/imunologia , Malária Falciparum/prevenção & controle , Plasmodium falciparum/imunologia , Proteínas de Protozoários/imunologia , Sensibilidade e Especificidade , Vacinas Sintéticas/administração & dosagem , Vacinas Sintéticas/imunologia
17.
Microb Pathog ; 132: 30-37, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31004723

RESUMO

Previous studies on vaccine development against foot-and-mouth disease (FMD) virus reported that application of the inactivated vaccines for FMD virus is not completely effective. Novel vaccinations based on immune-dominant epitopes showed they induced immune responses. In addition, for better and safer immunization, access to of efficient adjuvants against FMD virus seems to be critical. In this study, we produced epitope recombinant vaccines from the VP1 protein of the FMD virus for serotype O of Iran that conjugated with Fc Immunoglobulin (FcIgG) and Interleukin-2 (IL-2). Multiple-epitope constructs included Polytope, Polytope-IL2-FcIgG, Polytope-IL2, Polytope-FcIgG that cloned and expressed in E. coli BL21 (DE3). To evaluate whether these epitope recombinant vaccines induce immune responses, BALB/c mice were injected with the epitope recombinant vaccines and their immune responses were compared with a negative control group. The humoral and cellular immune responses were measured by ELISA. The results showed there were significant differences between the negative control group and other immunized mice with recombinant epitope proteins (p < 0.05). The results of total IgG, IgG1, IgG2a levels and secretion of IFN-γ, IL-4 and IL-10 revealed that immune responses were enhanced when the epitope recombinant vaccine of FMD virus coupled with IL-2 and FcIgG. Observations indicated that the epitope recombinant plasmid of the VP1 protein co-expressed with IL-2 and FcIgG was effective in inducing an enhanced immune response. Therefore, IL-2 and FcIgG could be recommended as a potential adjuvant for epitope recombinant vaccine of the VP1 protein from FMD virus.


Assuntos
Vírus da Febre Aftosa/imunologia , Febre Aftosa/imunologia , Imunização , Epitopos Imunodominantes/imunologia , Fragmentos Fc das Imunoglobulinas/imunologia , Interleucina-2/imunologia , Vacinas Sintéticas/imunologia , Vacinas Virais/imunologia , Adjuvantes Imunológicos , Animais , Anticorpos Antivirais , Proteínas do Capsídeo/genética , Proteínas do Capsídeo/imunologia , Modelos Animais de Doenças , Epitopos/genética , Epitopos/imunologia , Escherichia coli/genética , Feminino , Vírus da Febre Aftosa/genética , Imunidade Celular , Imunidade Humoral , Imunoglobulina G , Interferon gama , Interleucina-10 , Interleucina-2/genética , Interleucina-4 , Camundongos , Camundongos Endogâmicos BALB C , Modelos Moleculares , Vacinas Sintéticas/química , Vacinas Sintéticas/genética , Vacinas Virais/genética
18.
PLoS Negl Trop Dis ; 13(4): e0007345, 2019 04.
Artigo em Inglês | MEDLINE | ID: mdl-31009474

RESUMO

BACKGROUND: Human hookworms (Necator americanus, Ancylostoma duodenale, and Ancylostoma ceylanicum) are intestinal blood-feeding parasites that infect ~500 million people worldwide and are among the leading causes of iron-deficiency anemia in the developing world. Drugs are useful against hookworm infections, but hookworms rapidly reinfect people, and the parasites can develop drug resistance. Therefore, having a hookworm vaccine would be of tremendous benefit. METHODOLOGY/PRINCIPAL FINDINGS: We investigated the vaccine efficacy in outbred Syrian hamsters of three A. ceylanicum hookworm antigen candidates from two classes of proteins previously identified as promising vaccine candidates. These include two intestinally-enriched, putatively secreted cathepsin B cysteine proteases (AceyCP1, AceyCPL) and one small Kunitz-type protease inhibitor (AceySKPI3). Recombinant proteins were produced in Pichia pastoris, and adsorbed to Alhydrogel. Recombinant AceyCPL (rAceyCPL)/Alhydrogel and rAceySKPI3/Alhydrogel induced high serum immunoglobulin G (IgG) titers in 8/8 vaccinates, but were not protective. rAceyCP1/Alhydrogel induced intermediate serum IgG titers in ~60% of vaccinates in two different trials. rAceyCP1 serum IgG responders had highly significantly decreased hookworm burdens, fecal egg counts and clinical pathology compared to Alhydrogel controls and nonresponders. Protection was highly correlated with rAceyCP1 serum IgG titer. Antisera from rAceyCP1 serum IgG responders, but not nonresponders or rAceyCPL/Alhydrogel vaccinates, significantly reduced adult A. ceylanicum motility in vitro. Furthermore, rAceyCP1 serum IgG responders had canonical Th2-specific recall responses (IL4, IL5, IL13) in splenocytes stimulated ex vivo. CONCLUSIONS/SIGNIFICANCE: These findings indicate that rAceyCP1 is a promising vaccine candidate and validates a genomic/transcriptomic approach to human hookworm vaccine discovery.


Assuntos
Ancilostomíase/prevenção & controle , Anticorpos Anti-Helmínticos/sangue , Antígenos de Helmintos/imunologia , Cisteína Proteases/imunologia , Vacinação , Sequência de Aminoácidos , Ancylostoma/imunologia , Animais , Antígenos de Superfície/imunologia , Modelos Animais de Doenças , Imunoglobulina G/sangue , Enteropatias Parasitárias/prevenção & controle , Masculino , Mesocricetus , Proteínas Recombinantes/imunologia , Vacinas/imunologia , Vacinas Sintéticas
19.
Vet Ital ; 55(1): 73-79, 2019 Mar 31.
Artigo em Inglês | MEDLINE | ID: mdl-30951184

RESUMO

To evaluate the immunological response following vaccination, 40 WNV serologically negative horses were selected and divided in two groups of 20 animals. One group was vaccinated (booster after 28 days) with a whole inactivated viral strain and the second group with a live recombinant canarypox virus expressing the genes coding for the WNV preM/E viral proteins. IgM, IgG and neutralizing antibodies were monitored by class specific ELISAs and serum neutralization assay for 360 days. In both groups, IgM antibodies were first detected 7 days post vaccination (dpv). However, in the group vaccinated with inactivated vaccine, IgM antibodies were detected until day 42 pv, whereas in the group vaccinated with the recombinant vaccine, they were detected up to day 52 pv. A similar (P > 0.05) proportion of horses showed IgM antibodies after vaccination with either recombinant [30%; 95% confidence interval (CI): 14.59%-52.18%] or inactivated (32%; 95% CI: 15.39-54.28%) vaccine. Both vaccines induced in vaccinated horses a detectable IgG antibody response starting from day 7 pv and lasting till the end of the trial. Analogously, both products elicited WNV specific neutralizing antibodies. The response induced by the live canarypox virus-vectored vaccine was higher (mean titres 1:298 vs 1:18.9) and lasted longer than did that induced by the killed-virus vaccines. In fact, one year after the vaccination, neutralizing antibodies were still detectable in the horses which received the canarypox virus-based vaccine but not in the group vaccinated with the killed product. The use of vaccines is a valuable tool to prevent WNV disease in horses and the availability of different products facilitates the control of the disease in endemic areas.


Assuntos
Doenças dos Cavalos/imunologia , Febre do Nilo Ocidental/veterinária , Vacinas contra o Vírus do Nilo Ocidental/imunologia , Vírus do Nilo Ocidental/imunologia , Animais , Cavalos , Vacinas de Produtos Inativados/imunologia , Vacinas Sintéticas/imunologia , Febre do Nilo Ocidental/imunologia
20.
Microb Pathog ; 131: 181-185, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-30978430

RESUMO

Pseudomonas aeruginosa is a notorious pathogen with increasing multi-drug resistance. This situation makes it urgent to develop a prophylactic vaccine against this pathogen. Different virulence factors play a crucial role in P. aeruginosa infection. This study focused on evaluation of the iron acquisition protein HitA as a potential vaccine candidate against P. aeruginosa in a murine infection model. The recombinant ferric iron-binding periplasmic protein HitA was overexpressed in Escherichia coli and was purified using metal affinity chromatography. The purified antigen was administered to mice in combination with Bacillus Calmette-Guérin (BCG) as an adjuvant using different vaccination regimens. Serum samples were tested for IgG1, IgG2a and total IgG antibody responses which were extremely significant. Following challenge of mice with P. aeruginosa, there was a significant reduction in bacterial load in lungs of immunized mice compared to negative control mice. Opsonophagocytic assay supported the previous results. In addition, histopathological examination of livers of challenged mice showed a significant improvement difference between immunized mice and negative control mice in various histopathological parameters. Up to our knowledge, this is the first report that investigates HitA as a potential vaccine antigen. Overall, the results of this study demonstrate the protective effect of HitA recombinant protein and highlight its importance as a promising vaccine candidate against P. aeruginosa infection.


Assuntos
Vacinas Bacterianas/imunologia , Imunização , Ferro/química , Proteínas Periplásmicas/farmacologia , Infecções por Pseudomonas/imunologia , Infecções por Pseudomonas/prevenção & controle , Pseudomonas aeruginosa/imunologia , Adjuvantes Imunológicos , Animais , Anticorpos Antibacterianos/sangue , Carga Bacteriana , Modelos Animais de Doenças , Escherichia coli/genética , Feminino , Imunoglobulina G/sangue , Pulmão/microbiologia , Pulmão/patologia , Camundongos , Necrose , Periplasma , Proteínas Periplásmicas/genética , Infecções por Pseudomonas/patologia , Pseudomonas aeruginosa/patogenicidade , Proteínas Recombinantes , Vacinação , Vacinas Sintéticas
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA