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1.
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
2.
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
3.
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
4.
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
5.
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
6.
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
7.
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
8.
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
9.
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
10.
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
11.
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
12.
Vet Microbiol ; 232: 146-150, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-31030839

RESUMO

Newcastle disease virus (NDV) is a major threat to poultry worldwide. Virulent Newcastle disease virus infection can cause 100% morbidity and mortality in chickens. Vaccination is the most effective way to prevent and control NDV outbreaks in poultry. Previously, we demonstrated that a duck enteritis virus (DEV) vaccine strain is a promising vector to generate recombinant vaccines in chickens. Here, we constructed two recombinant DEVs expressing the F protein (rDEV-F) or HN protein (rDEV-HN) of NDV. We then evaluated the protective efficacy of these recombinant DEVs in specific-pathogen-free chickens. rDEV-F induced 100% protection of chickens from lethal NDV challenge after a single dose of 104 TCID50, whereas rDEV-HN did not induce effective protection. rDEV-F may therefore serve as a promising vaccine candidate for chickens. This is the first report of a DEV-vectored vaccine providing robust protection against lethal NDV infection in chickens.


Assuntos
Mardivirus/genética , Doença de Newcastle/prevenção & controle , Doenças das Aves Domésticas/prevenção & controle , Proteínas Virais de Fusão/imunologia , Vacinas Virais/imunologia , Animais , Anticorpos Antivirais , Galinhas/imunologia , Galinhas/virologia , Patos/virologia , Proteína HN/genética , Proteína HN/imunologia , Doença de Newcastle/imunologia , Vírus da Doença de Newcastle/genética , Vírus da Doença de Newcastle/imunologia , Doenças das Aves Domésticas/virologia , Organismos Livres de Patógenos Específicos , Vacinação , Vacinas Sintéticas/administração & dosagem , Vacinas Sintéticas/imunologia , Proteínas Virais de Fusão/genética , Vacinas Virais/administração & dosagem
13.
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
14.
Biomed Res Int ; 2019: 9630793, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30941374

RESUMO

Background: A recombinant BCG strain expressing the genetically detoxified S1 subunit of pertussis toxin 9K/129G (rBCG-S1PT), previously constructed by our research group, demonstrated the ability to develop high protection in mouse models of pertussis challenge which correlated with the induction of a Th1 immune response pattern. The Th1 immune response induced by rBCG-S1PT treatment was also confirmed in the murine orthotopic bladder cancer model, in which the intravesical instillation of rBCG-S1PT resulted in an improved antitumor effect. Based on these observations, we hypothesize that the reengineering of the S1PT expression in BCG could increase the efficiency of the protective Th1 immune response in order to develop a new alternative of immunotherapy in bladder cancer treatment. Objectives: To construct rBCG strains expressing S1PT from extrachromosomal (rBCG-S1PT) and integrative vectors (rBCG-Sli), or their combination, generating the bivalent strain (rBCG-S1+S1i), and to evaluate the respective immunogenicity of rBCG strains in mice. Methods: Mycobacterial plasmids were constructed by cloning the s1pt gene under integrative and extrachromosomal vectors and used to transform BCG, individually or in combination. Antigen expression and localization were confirmed by Western blot. Mice were immunized with wild-type BCG or the rBCG strains, and cytokines quantification and flow cytometry analysis were performed in splenocytes culture stimulated with mycobacterial-specific proteins. Findings: S1PT expression was confirmed in all rBCG strains. The extrachromosomal vector directs S1PT to the cell wall-associated fraction, while the integrative vector directs its expression mainly to the intracellular fraction. Higher levels of IFN-γ were observed in the splenocytes culture from the group immunized with rBCG-S1i in comparison to BCG or rBCG-S1PT. rBCG-S1+S1i showed higher levels of CD4+ IFN-γ + and double-positive CD4+ IFN-γ + TNF-α + T cells. Conclusions: rBCG-S1+S1i was able to express the two forms of S1PT and elicited higher induction of polyfunctional CD4+ T cells, indicating enhanced immunogenicity and suggesting its use as immunotherapy for bladder cancer.


Assuntos
Vacina BCG/imunologia , Linfócitos T CD4-Positivos/imunologia , Imunidade Celular , Mycobacterium bovis/fisiologia , Toxina Pertussis/metabolismo , Subunidades Proteicas/metabolismo , Vacinas Sintéticas/imunologia , Animais , Citocinas/biossíntese , Citocinas/metabolismo , Feminino , Imunização , Mediadores da Inflamação/metabolismo , Camundongos Endogâmicos BALB C , Fenótipo , Plasmídeos/metabolismo , Baço/citologia
15.
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
16.
Microb Pathog ; 131: 9-14, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-30930220

RESUMO

Acinetobacter baumannii is considered as a major cause of nosocomial infection worldwide. Various vaccine formulations have been mostly studied based on secreted or surface-exposed proteins of A. baumannii in murine models. Serum resistance proteins are critical virulence factors in bloodstream infections. AbOmpA and PKF are two major factors involved in serum resistance and could be considered as promising vaccine targets. In this study IgG1, IgG2c, Total-IgG concentrations, survival rates and spleen bacterial loads were studied in C57/BL mice model according to PKF, AbOmpA and AbOmpA + PKF vaccine formulations. The findings showed significant raises of IgG2c and Total-IgG in all three vaccinated groups in comparison with the control group. Whereas, there were low concentrations of IgG1 in all immunization plans. Colony counts of mice spleen showed the bacterial load of PKF plan had the most decrease of bacterial load (DBL = 5 log10 CFU/g). Taken together, this evaluation indicated that PKF vaccination plan induced a polarized Th1 response and rendered an effective protection against bloodstream infection caused by A. baumannii.


Assuntos
Infecções por Acinetobacter/imunologia , Infecções por Acinetobacter/prevenção & controle , Acinetobacter baumannii/patogenicidade , Formação de Anticorpos/imunologia , Proteínas da Membrana Bacteriana Externa/imunologia , Fatores R/sangue , Sepse/microbiologia , Infecções por Acinetobacter/microbiologia , Acinetobacter baumannii/genética , Animais , Carga Bacteriana , Proteínas da Membrana Bacteriana Externa/genética , Proteínas de Bactérias/genética , Proteínas de Bactérias/imunologia , Vacinas Bacterianas/imunologia , Clonagem Molecular , Modelos Animais de Doenças , Genes Bacterianos/genética , Imunização , Imunoglobulina G/sangue , Camundongos , Camundongos Endogâmicos C57BL , Fatores R/imunologia , Proteínas Recombinantes/genética , Proteínas Recombinantes/imunologia , Baço/imunologia , Taxa de Sobrevida , Vacinas Sintéticas/genética , Vacinas Sintéticas/imunologia , Fatores de Virulência/genética , Fatores de Virulência/imunologia
17.
MBio ; 10(2)2019 04 23.
Artigo em Inglês | MEDLINE | ID: mdl-31015334

RESUMO

Tick-borne encephalitis virus (TBEV), a member of the genus Flavivirus, is one of the most medically important tick-borne pathogens of the Old World. Despite decades of active research, attempts to develop of a live attenuated virus (LAV) vaccine against TBEV with acceptable safety and immunogenicity characteristics have not been successful. To overcome this impasse, we generated a chimeric TBEV that was highly immunogenic in nonhuman primates (NHPs). The chimeric virus contains the prM/E genes of TBEV, which are expressed in the genetic background of an antigenically closely related, but less pathogenic member of the TBEV complex-Langat virus (LGTV), strain T-1674. The neurovirulence of this chimeric virus was subsequently controlled by robust targeting of the viral genome with multiple copies of central nervous system-enriched microRNAs (miRNAs). This miRNA-targeted T/1674-mirV2 virus was highly stable in Vero cells and was not pathogenic in various mouse models of infection or in NHPs. Importantly, in NHPs, a single dose of the T/1674-mirV2 virus induced TBEV-specific neutralizing antibody (NA) levels comparable to those seen with a three-dose regimen of an inactivated TBEV vaccine, currently available in Europe. Moreover, our vaccine candidate provided complete protection against a stringent wild-type TBEV challenge in mice and against challenge with a parental (not miRNA-targeted) chimeric TBEV/LGTV in NHPs. Thus, this highly attenuated and immunogenic T/1674-mirV2 virus is a promising LAV vaccine candidate against TBEV and warrants further preclinical evaluation of its neurovirulence in NHPs prior to entering clinical trials in humans.IMPORTANCE Tick-borne encephalitis virus (TBEV) is one of the most medically important tick-borne pathogens of the Old World. Despite decades of active research, efforts to develop of TBEV live attenuated virus (LAV) vaccines with acceptable safety and immunogenicity characteristics have not been successful. Here we report the development and evaluation of a highly attenuated and immunogenic microRNA-targeted TBEV LAV.


Assuntos
Anticorpos Antivirais/sangue , Portadores de Fármacos , Vírus da Encefalite Transmitidos por Carrapatos/genética , Encefalite Transmitida por Carrapatos/prevenção & controle , Vetores Genéticos , Vacinas Virais/imunologia , Animais , Anticorpos Neutralizantes/sangue , Cercopithecus aethiops , Vírus da Encefalite Transmitidos por Carrapatos/crescimento & desenvolvimento , Vírus da Encefalite Transmitidos por Carrapatos/imunologia , Encefalite Transmitida por Carrapatos/imunologia , Camundongos , MicroRNAs/genética , MicroRNAs/metabolismo , Vacinas Atenuadas/administração & dosagem , Vacinas Atenuadas/efeitos adversos , Vacinas Atenuadas/genética , Vacinas Atenuadas/imunologia , Vacinas Sintéticas/administração & dosagem , Vacinas Sintéticas/efeitos adversos , Vacinas Sintéticas/genética , Vacinas Sintéticas/imunologia , Células Vero , Vacinas Virais/administração & dosagem , Vacinas Virais/efeitos adversos , Vacinas Virais/genética , Replicação Viral
18.
J Microbiol Biotechnol ; 29(4): 658-664, 2019 Apr 28.
Artigo em Inglês | MEDLINE | ID: mdl-30845792

RESUMO

Immunocontraception has been suggested as an optimal alternative to surgical contraception in animal species. Many immunocontraceptive vaccines have been designed to artificially produce antibodies against gonadotropin-releasing hormone-I (GnRH-I) which remove GnRH-I from the vaccinated animals. A deficiency of GnRH-I thereafter leads to a lack of gonadotropins, resulting in immunocontraception. In this study, we initially developed three immunocontraceptive vaccines composed of GnRH-I, GnRH-II, and a GnRH-I and -II (GnRHI+ II) complex, conjugated to the external domain of Salmonella Typhimurium flagellin. As the GnRH-I+II vaccine induced significantly (p < 0.01) higher levels of anti-GnRH-I antibodies than the other two vaccines, we further evaluated its immunocontraceptive effects in male rats. Mean testis weight in rats (n = 6) inoculated twice with the GnRH-I+II vaccine at 2-week intervals was significantly (p < 0.01) lower than in negative control rats at 10 weeks of age. Among the six vaccinated rats, two were non-responders whose testes were not significantly reduced when compared to those of negative control rats. Significantly smaller testis weight (p < 0.001), higher anti-GnRH-I antibody levels (p < 0.001), and lower testosterone levels (p < 0.001) were seen in the remaining four responders compared to the negative control rats at the end of the experiments. Furthermore, seminiferous tubule atrophy and spermatogenesis arrest were found in the testis tissues of responders. Therefore, the newly developed GnRH-I+II vaccine efficiently induced immunocontraception in male rats. This vaccine can potentially also be applied for birth control in other animal species.


Assuntos
Anticoncepção Imunológica , Hormônio Liberador de Gonadotropina/análogos & derivados , Hormônio Liberador de Gonadotropina/imunologia , Imunização , Vacinação , Animais , Anticorpos , Flagelina/imunologia , Hormônio Liberador de Gonadotropina/genética , Imunização/efeitos adversos , Masculino , Ratos , Proteínas Recombinantes/imunologia , Salmonella typhimurium , Túbulos Seminíferos/patologia , Espermatogênese , Testículo/patologia , Testosterona/sangue , Vacinas Conjugadas , Vacinas Sintéticas/imunologia
19.
J Microbiol Biotechnol ; 29(4): 651-657, 2019 Apr 28.
Artigo em Inglês | MEDLINE | ID: mdl-30856707

RESUMO

Although smallpox was eradicated in 1980, it is still considered a potential agent of biowarfare and bioterrorism. Smallpox has the potential for high mortality rates along with a major public health impact, eventually causing public panic and social disruption. Passive administration of neutralizing monoclonal antibodies (mAbs) is an effective intervention for various adverse reactions caused by vaccination and the unpredictable nature of emerging and bioterrorist-related infections. Currently, vaccinia immune globulin (VIG) is manufactured from vaccinia vaccine-boosted plasma; however, this production method is not ideal because of its limited availability, low specific activity, and risk of contamination with blood-borne infectious agents. To overcome the limitations of VIG production from human plasma, we isolated two human single chain variable fragments (scFvs) (SC34 and SC212) bound to vaccinia virus (VACV) from a scFv phage library constructed from the B cells of VACV vaccine-boosted volunteers. The scFvs were converted to human IgG1 (VC34 and VC212). These two anti-VACV mAbs were produced in Chinese Hamster Ovary (CHO) DG44 cells. The binding affinities of VC34 and VC212 were estimated by competition ELISA to IC50 values of 2 µg/mL (13.33 nM) and 22 µg/mL (146.67 nM), respectively. Only the VC212 mAb was proven to neutralize the VACV, as evidenced by the plaque reduction neutralization test (PRNT) result with a PRNT50 of ~0.16 mg/mL (~1.07 µM). This VC212 could serve as a valuable starting material for further development of VACV-neutralizing human immunoglobulin for a prophylactic measure against post-vaccination complications and for post-exposure treatment against smallpox.


Assuntos
Anticorpos Neutralizantes/imunologia , Anticorpos Antivirais/imunologia , Bacteriófagos , Técnicas de Visualização da Superfície Celular/métodos , Anticorpos de Cadeia Única/imunologia , Varíola/prevenção & controle , Vacinas Sintéticas/imunologia , Vírus Vaccinia/imunologia , Sequência de Aminoácidos , Animais , Anticorpos Monoclonais/imunologia , Anticorpos Antivirais/biossíntese , Anticorpos Antivirais/genética , Linfócitos B , Bioterrorismo , Células CHO , Clonagem Molecular , Cricetinae , Cricetulus , Escherichia coli/genética , Biblioteca Gênica , Humanos , Imunoglobulina G , Imunoglobulinas/genética , Testes de Neutralização , Fatores de Processamento de Serina-Arginina/isolamento & purificação , Anticorpos de Cadeia Única/genética , Anticorpos de Cadeia Única/isolamento & purificação , Varíola/imunologia , Vacina Antivariólica/imunologia , Vacinação , Vacinas Sintéticas/genética , Vacinas Sintéticas/uso terapêutico , Vírus Vaccinia/genética
20.
J Fish Dis ; 42(5): 631-642, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-30874325

RESUMO

Infectious hematopoietic necrosis virus (IHNV) and infectious pancreatic necrosis virus (IPNV) are important pathogens in rainbow trout farming worldwide. Their co-infection is also common, which causes great economic loss in juvenile salmon species. Development of a universal virus vaccine providing broadly cross-protective immunity will be of great importance. In this study, we generated two recombinant (r) virus (rIHNV-N438A-ΔNV-EGFP and rIHNV-N438A-ΔNV-VP2) replacing the NV gene of the backbone of rIHNV at the single point mutation at residue 438 with an efficient green fluorescent protein (EGFP) reporter gene and antigenic VP2 gene of IPNV. Meanwhile, we tested their efficacy against the wild-type (wt) IHNV HLJ-09 virus and IPNV serotype Sp virus challenge. The relative per cent survival rates of two recombinant viruses against (wt) IHNV HLJ-09 virus challenge were 84.6% and 81.5%, respectively. Simultaneously, the relative per cent survival rate of rIHNV-N438A-ΔNV-VP2 against IPNV serotype Sp virus challenge was 88.9%. It showed the two recombinant viruses had high protection rates and induced a high level of antibodies against IHNV or IPNV. Taken together, these results suggest the VP2 gene of IPNV can act as candidate gene for vaccine and attenuated multivalent live vaccines and molecular marker vaccines have potential application for viral vaccine.


Assuntos
Imunidade Adaptativa , Doenças dos Peixes/prevenção & controle , Vírus da Necrose Hematopoética Infecciosa/imunologia , Vírus da Necrose Pancreática Infecciosa/imunologia , Oncorhynchus mykiss , Vacinas Virais/imunologia , Animais , Infecções por Birnaviridae/imunologia , Infecções por Birnaviridae/prevenção & controle , Infecções por Birnaviridae/veterinária , Doenças dos Peixes/imunologia , Vírus da Necrose Hematopoética Infecciosa/genética , Vírus da Necrose Pancreática Infecciosa/genética , Distribuição Aleatória , Infecções por Rhabdoviridae/imunologia , Infecções por Rhabdoviridae/prevenção & controle , Infecções por Rhabdoviridae/veterinária , Vacinas Sintéticas/administração & dosagem , Vacinas Sintéticas/genética , Vacinas Sintéticas/imunologia , Vacinas Virais/administração & dosagem , Vacinas Virais/genética
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