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1.
APMIS ; 127(12): 753-763, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31512768

RESUMO

Iron uptake system is expressed in early stages of Acinetobacter baumannii infections under iron-restricted conditions. This study is aimed at the evaluation of immuno-protectivity of BfnH in comparison with BauA in both mature and selected fragmental proteins. The study was designed in single and combined forms of antigens. BfnH is presented in 3472 strains of A. baumannii with more than 97% identity. The preliminary immune-informatics analysis of this protein indicated a region from the ß-barrel domain including exposed loops 2-5, with antigenic score comparable to that of BfnH. There was a significant rise in the specific IgG response in all test groups. The bacterial challenge with a lethal dose of A. baumannii demonstrated partial protection of whole proteins which coincides with a significant reduction in the bacterial population colonized in the main organs and an increase in the survival level. Passive immunization of the mice brought about 50% survival in the mice groups immunized with BfnH and with a combination of BfnH and BauA. The protectivity of siderophore receptors suggests their potential immunogenic role that could be considered as a component of multivalent subunit vaccine candidates against A. baumannii.


Assuntos
Infecções por Acinetobacter/prevenção & controle , Acinetobacter baumannii/imunologia , Proteínas da Membrana Bacteriana Externa/imunologia , Imunização , Receptores de Superfície Celular/imunologia , Infecções por Acinetobacter/imunologia , Infecções por Acinetobacter/microbiologia , Animais , Anticorpos Antibacterianos/sangue , Anticorpos Antibacterianos/imunologia , Carga Bacteriana , Proteínas da Membrana Bacteriana Externa/química , Proteínas da Membrana Bacteriana Externa/genética , Vacinas Bacterianas/administração & dosagem , Vacinas Bacterianas/imunologia , Epitopos de Linfócito B , Feminino , Imunogenicidade da Vacina , Camundongos Endogâmicos BALB C , Receptores de Superfície Celular/química , Receptores de Superfície Celular/genética
2.
Acta Virol ; 63(3): 301-308, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31507196

RESUMO

Transmissible gastroenteritis virus (TGEV) causes great economic loss to swine industry worldwide. Vaccination is an important method to control the TGEV infection. In this study, a TGEV oral vaccine was generated by transferring a eukaryotic expression recombinant plasmid carrying the SAD (A and D antigenic sites of the S protein) epitope of TGEV into a swine-origin Lactobacillus acidophilus (L. acidophilus). In orally immunized BALB/c mice, the TGEV L. acidophilus oral vaccine induced significantly higher level of SIgA antibodies specific to TGEV compared with the mice immunized with a commercial inactivated TGEV vaccine and similar levels of IgG specific to TGEV as the inactivated vaccine. Furthermore, the TGEV L. acidophilus oral vaccine induced higher levels of IFN-γ, which suggested that the vaccine was able to induce immune response. In brief, this novel TGEV L. acidophilus oral vaccine could induce high levels of both mucosal and humoral immune responses, which has a potential to be used in the pig industries in the future. Keywords: transmissible gastroenteritis virus (TGEV); live L. acidophilus oral vaccine; SIgA antibody; IgG antibody; IFN-γ; IL-4.


Assuntos
Anticorpos Antivirais , Epitopos , Gastroenterite Suína Transmissível , Lactobacillus acidophilus , Vírus da Gastroenterite Transmissível , Vacinas Virais , Administração Oral , Animais , Anticorpos Antivirais/sangue , Epitopos/genética , Epitopos/imunologia , Gastroenterite Suína Transmissível/imunologia , Gastroenterite Suína Transmissível/patologia , Imunogenicidade da Vacina/imunologia , Lactobacillus acidophilus/genética , Lactobacillus acidophilus/virologia , Camundongos , Camundongos Endogâmicos BALB C , Plasmídeos/genética , Suínos , Proteínas Virais/genética , Proteínas Virais/imunologia , Vacinas Virais/administração & dosagem , Vacinas Virais/imunologia
3.
Zhonghua Yu Fang Yi Xue Za Zhi ; 53(8): 851-854, 2019 Aug 06.
Artigo em Chinês | MEDLINE | ID: mdl-31378048

RESUMO

There are many limitations in evaluating vaccine efficacy by comparing the incidence of clinical endpoint events (such as morbidity, bacterial colonization) between the vaccine group and the control group. Therefore, the researchers put forward the concept of Surrogate of protection to predict vaccine protection with immunological indicators. In 2012, WHO put forward the immunological substitution endpoint of pneumococcal vaccine, using 0. 35 µg/ml as the protective antibody level of pneumococcal vaccine. But subsequent studies have found that using this threshold to assess all vaccine serotypes may not be accurate.


Assuntos
Imunogenicidade da Vacina , Infecções Pneumocócicas/prevenção & controle , Vacinas Pneumocócicas/uso terapêutico , Anticorpos Antibacterianos/sangue , Humanos , Vacinas Conjugadas/uso terapêutico
4.
Vet Immunol Immunopathol ; 215: 109884, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31420066

RESUMO

Many vaccines against childhood diseases are administered early after birth, but vaccine development studies frequently test efficacy in adult rather than in neonatal animal models. In countries with endemic tuberculosis (TB), Bacillus Calmette-Guerin (BCG) is administered as part of the neonatal vaccine regimen because it prevents against the disseminated form of TB in children, although it has variable efficacy against pulmonary TB. Several promising new vaccines against TB are currently being tested in adult animal models. Here we evaluated neonatal piglets as an animal model to test vaccine efficacy. For this purpose, minipigs were vaccinated or not with BCG 48 h after birth and their immune response followed longitudinally until adolescence. We characterized the memory and activation phenotype of T cells, cytokine profile, and monocyte activation in response to BCG stimulation from 4 weeks of age into adolescence- age of 24 weeks. Immunological responses in vaccinated and non-vaccinated animals were further monitored upon infection with a low dose exposure to Mycobacterium tuberculosis strain HN878 via the aerosol route. Comparing the immunological response elicited by BCG vaccination in minipigs vs similar studies in infants, suggest that minipigs have the potential to serve as an effective neonatal animal model for vaccine development.


Assuntos
Vacina BCG/imunologia , Modelos Animais de Doenças , Mycobacterium tuberculosis/imunologia , Porco Miniatura/imunologia , Tuberculose Pulmonar/imunologia , Animais , Animais Recém-Nascidos , Citocinas/metabolismo , Avaliação Pré-Clínica de Medicamentos/métodos , Feminino , Imunogenicidade da Vacina , Memória Imunológica , Imunofenotipagem , Estudos Longitudinais , Ativação Linfocitária , Masculino , Monócitos/imunologia , Suínos , Tuberculose/imunologia , Tuberculose Pulmonar/prevenção & controle
5.
Vet Immunol Immunopathol ; 213: 109888, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31307673

RESUMO

Felis catus papillomavirus type 2 (FcaPV-2) commonly infects the skin of domestic cats and has been associated with the development of skin cancer. In the present study, a FcaPV-2 virus-like particle (VLP) vaccine was produced and assessed for vaccine safety, immunogenicity, and impact on FcaPV-2 viral load. This is the first report of the use of a papillomavirus VLP vaccine in domestic cats. The FcaPV-2 VLP vaccine was given to ten adult cats that were naturally infected with FcaPV-2, and a further ten naturally infected cats were sham vaccinated as a control group. The rationale for vaccinating cats already infected with the virus was to induce neutralizing antibody titers that could prevent reinfection of new areas of skin and reduce the overall viral load, as has been demonstrated in other species. Reducing the overall FcaPV-2 viral load could reduce the risk for subsequent PV-associated cancer. The vaccine in this study was well-tolerated, as none of the cats developed any signs of local reaction or systemic illness. In the treatment group, the geometric mean anti-papillomavirus endpoint antibody titers increased significantly following vaccination from 606 (95% CI 192-1913) to 4223 (2023-8814), a 7.0-fold increase, although the individual antibody response varied depending on the level of pre-existing antibodies. Despite the immunogenicity of the vaccine, there was no significant change in FcaPV-2 viral load in the treatment group compared to the control group, over the 24 week follow-up period. A possible reason is that FcaPV-2 was already widespread in the basal skin layer of these adult cats and so preventing further cells from becoming infected had no impact on the overall viral load. Therefore, these results do not support the use of a FcaPV-2 VLP vaccine to reduce the risk for PV-associated cancer in cats in which FcaPV-2 infection is already well established. However, these results justify future studies in which the vaccine is administered to younger cats prior to FcaPV-2 infection becoming fully established.


Assuntos
Doenças do Gato/prevenção & controle , Imunogenicidade da Vacina , Infecções por Papillomavirus/veterinária , Neoplasias Cutâneas/veterinária , Carga Viral , Vacinas Virais/imunologia , Animais , Anticorpos Antivirais/sangue , Doenças do Gato/virologia , Gatos , DNA Viral/sangue , Feminino , Masculino , Papillomaviridae/genética , Papillomaviridae/imunologia , Infecções por Papillomavirus/prevenção & controle , Reação em Cadeia da Polimerase , Testes Sorológicos , Pele/patologia , Pele/virologia , Neoplasias Cutâneas/prevenção & controle , Neoplasias Cutâneas/virologia , Vacinas de Partículas Semelhantes a Vírus/imunologia
6.
J Dairy Sci ; 102(9): 8376-8384, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31301846

RESUMO

Little is known about the influence of maternal antibodies and immune cells transferred through colostrum on the immune responses of calves to the currently used foot-and-mouth disease (FMD) vaccines. Here we evaluated the humoral and cellular immune responses induced by vaccination of colostrum-deprived calves and calves that received equivalent amounts of colostrum preparations that differed in the presence or absence of maternal immune cells but contained the same quantity and quality of anti-foot-and-mouth disease virus (FMDV) antibodies. Three groups of 32-d-old calves (n = 3 per group) were deprived of colostrum and fed either whole immune colostrum or a cell-free colostrum preparation containing only anti-FMDV antibodies. All groups were immunized with 1 dose of an oil-adjuvanted commercial vaccine. Blood samples were collected periodically before vaccination and weekly after vaccination. Immune responses specific to FMDV were assessed based on T-cell proliferation, IFN-γ production, total and neutralizing serum antibodies, and isotype profile. All vaccinated calves developed IFN-γ and lymphoproliferative responses, irrespective of the colostrum received. Colostrum-deprived animals responded to vaccination with a primary IgM response followed by an increase of IgG1 titers. Conversely, antibody titers decreased in all colostrum-fed calves after vaccination. This study demonstrates for the first time that maternal immune cells transferred to the calves through colostrum do not modify immune responses to FMD vaccine, and it confirms the interference of maternal antibodies in the induction of humoral but not cell-mediated immune responses.


Assuntos
Doenças dos Bovinos/imunologia , Colostro/imunologia , Febre Aftosa/imunologia , Vacinas Virais/imunologia , Adjuvantes Imunológicos , Animais , Anticorpos Antivirais/sangue , Bovinos , Doenças dos Bovinos/prevenção & controle , Feminino , Imunidade Celular , Imunogenicidade da Vacina , Gravidez , Vacinação/veterinária
7.
Vet J ; 249: 67-72, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31239168

RESUMO

Vaccination of pigs against Salmonella Typhimurium (S. Typhimurium) can be effective for the control of Salmonella infections at the farm level and reduce the risk of Salmonella contamination in the food chain. However, vaccination may interfere with herd serological status in serology-based Salmonella monitoring programs. The present study investigated the effects of an attenuated S. Typhimurium vaccine (Salmoporc, IDT Biologika) on Salmonella serology in sows, neonatal piglets and slaughter pigs from three subclinically infected herds. Within each herd, five different vaccination protocols were tested as follows: group 1, vaccination of sows; group 2, vaccination of sows and piglets; group 3, vaccination of sows and fattening pigs; group 4, vaccination of piglets; and group 5 vaccination of fattening pigs. Each group was compared to a non-vaccinated control group (group 6). Sera were analyzed by ELISA (HerdChek Swine Salmonella, IDEXX Laboratories) and sample-to-positive (S/P) ratios were calculated. At day 3 after farrowing, but not before vaccination, S/P ratios in vaccinated sows (mean: 2.21) were significantly higher than S/P ratios in non-vaccinated sows (mean: 0.87, P<0.001). S/P ratios in 3-day old piglets from vaccinated sows (mean: 2.46) were significantly higher than S/P ratios in similar piglets from non-vaccinated sows (mean: 0.73, P<0.001). At slaughter, S/P ratios in pigs from groups 2, 3, 4 and 5 were significantly higher than those in the non-vaccinated control group (P<0.001). Therefore, vaccination of piglets and fattening pigs could have implications for current serology-based Salmonella monitoring programs in slaughter pigs.


Assuntos
Salmonelose Animal/prevenção & controle , Vacinas contra Salmonella/administração & dosagem , Salmonella typhimurium , Doenças dos Suínos/prevenção & controle , Agricultura , Animais , Anticorpos Antibacterianos/sangue , Feminino , Imunogenicidade da Vacina , Salmonelose Animal/imunologia , Vacinas contra Salmonella/imunologia , Suínos , Doenças dos Suínos/imunologia , Vacinas Atenuadas/administração & dosagem , Vacinas Atenuadas/imunologia
8.
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
9.
Cancer Immunol Immunother ; 68(8): 1245-1261, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31222486

RESUMO

The efficacy of cancer immunotherapy, including treatment with immune-checkpoint inhibitors, often is limited by ineffective presentation of antigenic peptides that elicit T-cell-mediated anti-tumor cytotoxic responses. Manipulation of antigen presentation pathways is an emerging approach for enhancing the immunogenicity of tumors in immunotherapy settings. ER aminopeptidase 1 (ERAP1) is an intracellular enzyme that trims peptides as part of the system that generates peptides for binding to MHC class I molecules (MHC-I). We hypothesized that pharmacological inhibition of ERAP1 in cells could regulate the cellular immunopeptidome. To test this hypothesis, we treated A375 melanoma cells with a recently developed potent ERAP1 inhibitor and analyzed the presented MHC-I peptide repertoire by isolating MHC-I, eluting bound peptides, and identifying them using capillary chromatography and tandem mass spectrometry (LC-MS/MS). Although the inhibitor did not reduce cell-surface MHC-I expression, it induced qualitative and quantitative changes in the presented peptidomes. Specifically, inhibitor treatment altered presentation of about half of the total 3204 identified peptides, including about one third of the peptides predicted to bind tightly to MHC-I. Inhibitor treatment altered the length distribution of eluted peptides without change in the basic binding motifs. Surprisingly, inhibitor treatment enhanced the average predicted MHC-I binding affinity, by reducing presentation of sub-optimal long peptides and increasing presentation of many high-affinity 9-12mers, suggesting that baseline ERAP1 activity in this cell line is destructive for many potential epitopes. Our results suggest that chemical inhibition of ERAP1 may be a viable approach for manipulating the immunopeptidome of cancer.


Assuntos
Aminopeptidases/metabolismo , Antígenos de Neoplasias/metabolismo , Antineoplásicos/farmacologia , Vacinas Anticâncer/imunologia , Epitopos de Linfócito T/metabolismo , Imunoterapia/métodos , Melanoma/tratamento farmacológico , Antígenos de Histocompatibilidade Menor/metabolismo , Peptídeos/metabolismo , Inibidores de Proteases/farmacologia , Linfócitos T Citotóxicos/imunologia , Aminopeptidases/antagonistas & inibidores , Apresentação do Antígeno , Antígenos de Neoplasias/genética , Antígenos de Neoplasias/imunologia , Linhagem Celular Tumoral , Citotoxicidade Imunológica , Epitopos de Linfócito T/genética , Epitopos de Linfócito T/imunologia , Antígenos HLA/metabolismo , Antígenos de Histocompatibilidade Classe I/metabolismo , Humanos , Imunogenicidade da Vacina , Ativação Linfocitária , Terapia de Alvo Molecular , Peptídeos/genética , Peptídeos/imunologia , Ligação Proteica
10.
Int J Mol Sci ; 20(11)2019 May 30.
Artigo em Inglês | MEDLINE | ID: mdl-31151230

RESUMO

Cytomegalovirus (CMV) infection after hematopoietic stem cell transplantation (HSCT) is one of the critical infectious complications related to host immune recovery. The spectrum of CMV infection is quite extensive, from asymptomatic CMV reactivation presenting mainly as CMV DNAemia to fatal CMV diseases involving gut, liver, lungs, or brain. In addition to organ involvement, CMV reactivation can exert indirect effects such as immunosuppression or graft failure that may result in the development of concurrent infectious complications. Currently, preemptive therapy, which is based on PCR-based monitoring of CMV from blood, is a mainstay enabling improvement in CMV-related outcomes. During the past decades, new antiviral drugs, clinical trials for prophylaxis in high-risk groups, and vaccines for preventing CMV infection have been introduced. In addition, data for immunologic monitoring and adoptive immunotherapy have also been accumulated. Here, we review the current status and recent updates in this field, with future perspectives including immunotherapy in HSCT recipients.


Assuntos
Infecções por Citomegalovirus/etiologia , Infecções por Citomegalovirus/terapia , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Antivirais/uso terapêutico , Ensaios Clínicos como Assunto , Citomegalovirus/imunologia , Vacinas contra Citomegalovirus/administração & dosagem , Vacinas contra Citomegalovirus/imunologia , Transplante de Células-Tronco Hematopoéticas/métodos , Interações Hospedeiro-Patógeno/imunologia , Humanos , Hospedeiro Imunocomprometido , Imunogenicidade da Vacina , Imunoterapia , Vigilância em Saúde Pública , Padrão de Cuidado , Condicionamento Pré-Transplante , Transplante Homólogo , Resultado do Tratamento
12.
Lancet ; 394(10193): 148-158, 2019 07 13.
Artigo em Inglês | MEDLINE | ID: mdl-31174831

RESUMO

BACKGROUND: Use of oral live-attenuated polio vaccines (OPV), and injected inactivated polio vaccines (IPV) has almost achieved global eradication of wild polio viruses. To address the goals of achieving and maintaining global eradication and minimising the risk of outbreaks of vaccine-derived polioviruses, we tested novel monovalent oral type-2 poliovirus (OPV2) vaccine candidates that are genetically more stable than existing OPVs, with a lower risk of reversion to neurovirulence. Our study represents the first in-human testing of these two novel OPV2 candidates. We aimed to evaluate the safety and immunogenicity of these vaccines, the presence and extent of faecal shedding, and the neurovirulence of shed virus. METHODS: In this double-blind, single-centre phase 1 trial, we isolated participants in a purpose-built containment facility at the University of Antwerp Hospital (Antwerp, Belgium), to minimise the risk of environmental release of the novel OPV2 candidates. Participants, who were recruited by local advertising, were adults (aged 18-50 years) in good health who had previously been vaccinated with IPV, and who would not have any contact with immunosuppressed or unvaccinated people for the duration of faecal shedding at the end of the study. The first participant randomly chose an envelope containing the name of a vaccine candidate, and this determined their allocation; the next 14 participants to be enrolled in the study were sequentially allocated to this group and received the same vaccine. The subsequent 15 participants enrolled after this group were allocated to receive the other vaccine. Participants and the study staff were masked to vaccine groups until the end of the study period. Participants each received a single dose of one vaccine candidate (candidate 1, S2/cre5/S15domV/rec1/hifi3; or candidate 2, S2/S15domV/CpG40), and they were monitored for adverse events, immune responses, and faecal shedding of the vaccine virus for 28 days. Shed virus isolates were tested for the genetic stability of attenuation. The primary outcomes were the incidence and type of serious and severe adverse events, the proportion of participants showing viral shedding in their stools, the time to cessation of viral shedding, the cell culture infective dose of shed virus in virus-positive stools, and a combined index of the prevalence, duration, and quantity of viral shedding in all participants. This study is registered with EudraCT, number 2017-000908-21 and ClinicalTrials.gov, number NCT03430349. FINDINGS: Between May 22 and Aug 22, 2017, 48 volunteers were screened, of whom 15 (31%) volunteers were excluded for reasons relating to the inclusion or exclusion criteria, three (6%) volunteers were not treated because of restrictions to the number of participants in each group, and 30 (63%) volunteers were sequentially allocated to groups (15 participants per group). Both novel OPV2 candidates were immunogenic and increased the median blood titre of serum neutralising antibodies; all participants were seroprotected after vaccination. Both candidates had acceptable tolerability, and no serious adverse events occurred during the study. However, severe events were reported in six (40%) participants receiving candidate 1 (eight events) and nine (60%) participants receiving candidate 2 (12 events); most of these events were increased blood creatinine phosphokinase but were not accompanied by clinical signs or symptoms. Vaccine virus was detected in the stools of 15 (100%) participants receiving vaccine candidate 1 and 13 (87%) participants receiving vaccine candidate 2. Vaccine poliovirus shedding stopped at a median of 23 days (IQR 15-36) after candidate 1 administration and 12 days (1-23) after candidate 2 administration. Total shedding, described by the estimated median shedding index (50% cell culture infective dose/g), was observed to be greater with candidate 1 than candidate 2 across all participants (2·8 [95% CI 1·8-3·5] vs 1·0 [0·7-1·6]). Reversion to neurovirulence, assessed as paralysis of transgenic mice, was low in isolates from those vaccinated with both candidates, and sequencing of shed virus indicated that there was no loss of attenuation in domain V of the 5'-untranslated region, the primary site of reversion in Sabin OPV. INTERPRETATION: We found that the novel OPV2 candidates were safe and immunogenic in IPV-immunised adults, and our data support the further development of these vaccines to potentially be used for maintaining global eradication of neurovirulent type-2 polioviruses. FUNDING: Bill & Melinda Gates Foundation.


Assuntos
Imunogenicidade da Vacina , Vacina Antipólio Oral/efeitos adversos , Vacina Antipólio Oral/imunologia , Poliovirus/imunologia , Adulto , Anticorpos Antivirais/sangue , Método Duplo-Cego , Fezes/virologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Poliomielite/prevenção & controle , Vacina Antipólio Oral/administração & dosagem , RNA Viral/análise , Método Simples-Cego , Vacinas Atenuadas/administração & dosagem , Vacinas Atenuadas/efeitos adversos , Vacinas Atenuadas/imunologia , Virulência/imunologia , Eliminação de Partículas Virais/imunologia , Adulto Jovem
13.
Vet Microbiol ; 233: 113-117, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31176396

RESUMO

Bovine ephemeral fever virus (BEFV) causes an acute febrile disease in cattle and water buffalo. The disease has an impact on dairy and beef production in tropical and subtropical countries. Vaccination is used for disease prevention and control. In this study, we developed a recombinant lentivirus to produce mammalian stable cells expressing histidine-tagged BEFV G protein with a deleted transmembrane domain (GΔTM) as a secretory protein. In addition, guinea pigs were immunised with the purified GΔTM protein and booster immunised at a 3-week interval. The mammalian stable cells were able to continuously produce GΔTM protein for a minimum of 25 passages. All of the mammalian stable cells expressing GΔTM protein could react specifically with a BEFV convalescent bovine serum. Serum samples from the immunised guinea pigs could react strongly and specifically with the purified GΔTM protein. Moreover, post-immunised guinea pig sera contained antibodies that could neutralise BEFV. These results indicate that the G protein without a transmembrane domain can be used as a subunit vaccine for the prevention and control of BEFV. The availability of the mammalian stable cells, which constitutively express GΔTM protein, could facilitate the potential use of the secretory protein for BEFV diagnosis and vaccine development.


Assuntos
Anticorpos Antivirais/sangue , Febre Efêmera/prevenção & controle , Glicoproteínas/genética , Glicoproteínas/imunologia , Imunogenicidade da Vacina , Proteínas Virais/genética , Proteínas Virais/imunologia , Animais , Anticorpos Neutralizantes/sangue , Bovinos , Linhagem Celular , Febre Efêmera/imunologia , Vírus da Febre Efêmera Bovina , Feminino , Cobaias , Células HEK293 , Humanos , Transfecção , Vacinação , Vacinas Virais/imunologia
14.
Cancer Immunol Immunother ; 68(7): 1143-1155, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31177328

RESUMO

Enhancement of endogenous immunity to tumor-associated self-antigens and neoantigens is the goal of preventive vaccination. Toward this goal, we compared the efficacy of the following HER2 DNA vaccine constructs: vaccines encoding wild-type HER2, hybrid HER2 vaccines consisting of human HER2 and rat Neu, HER2 vaccines with single residue substitutions and a novel human HER2 DNA vaccine, ph(es)E2TM. ph(es)E2TM was designed to contain five evolution-selected substitutions: M198V, Q398R, F425L, H473R and A622T that occur frequently in 12 primate HER2 sequences. These ph(es)E2TM substitutions score 0 to 1 in blocks substitutions matrix (BLOSUM), indicating minimal biochemical alterations. h(es)E2TM recombinant protein is recognized by a panel of anti-HER2 mAbs, demonstrating the preservation of HER2 protein structure. Compared to native human HER2, electrovaccination of HER2 transgenic mice with ph(es)E2TM induced a threefold increase in HER2-binding antibody (Ab) and elevated levels of IFNγ-producing T cells. ph(es)E2TM, but not pE2TM immune serum, recognized HER2 peptide p95 355LPESFDGDPASNTAP369, suggesting a broadening of epitope recognition induced by the minimally modified HER2 vaccine. ph(es)E2TM vaccination reduced tumor growth more effectively than wild-type HER2 or HER2 vaccines with more extensive modifications. The elevation of tumor immunity by ph(es)E2TM vaccination would create a favorable tumor microenvironment for neoantigen priming, further enhancing the protective immunity. The fundamental principle of exploiting evolution-selected amino acid substitutions is novel, effective and applicable to vaccine development in general.


Assuntos
Antígenos de Neoplasias/imunologia , Vacinas Anticâncer/imunologia , Imunoterapia/métodos , Neoplasias Mamárias Experimentais/terapia , Receptor ErbB-2/imunologia , Substituição de Aminoácidos/genética , Substituição de Aminoácidos/imunologia , Animais , Antígenos de Neoplasias/genética , Vacinas Anticâncer/genética , Vacinas Anticâncer/uso terapêutico , Linhagem Celular Tumoral/transplante , Células Dendríticas/imunologia , Evolução Molecular , Feminino , Imunogenicidade da Vacina/genética , Neoplasias Mamárias Experimentais/genética , Neoplasias Mamárias Experimentais/imunologia , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Transgênicos , Receptor ErbB-2/genética , Proteínas Recombinantes/genética , Proteínas Recombinantes/imunologia , Tolerância a Antígenos Próprios/genética , Microambiente Tumoral/imunologia , Vacinas de DNA/genética , Vacinas de DNA/imunologia , Vacinas de DNA/uso terapêutico
15.
Microb Pathog ; 132: 243-253, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31075428

RESUMO

Ebola virus (EBOV), a non-segmented single-stranded RNA virus, is often-most transmitted through body fluids like sweat, tears, saliva, and nasal secretions. Till date, there is no licensed vaccine of EBOV is available in the market; however, the world is increasingly vulnerable to this emerging threat. Hence, it is the need of time to develop a vaccine for EBOV to hinder its dissemination. The current study has been designed for identification and characterization of the potential B and T-cell epitopes using the Immuno-informatics tools, and it helped in finding the potent vaccine candidates against EBOV. Prediction, antigenicity and allergenicity testing of predicted B and T cells' epitopes was done as well to identify their potential as a vaccine candidate and to measure their safety level respectively. Among B-cell epitopes "WIPAGIGVTGVIIA" showed a high antigenicity score and it would play an important role in evoking the immune response. In T-cell epitopes, peptides "AIGLAWIPY" and "IRGFPRCRY" presented high antigenicity score, which binds to MHC class-I and MHC class-II alleles respectively. All predicted epitopes were analyzed and compared with already reported peptides carefully. Comparatively, Peptides predicted in the present study showed more immunogenicity score than already reported peptides, used as positive control, and are more immunogenic as compared to them. Peptides reported in the present study do not target only Zaire EBOV (ZEBOV), as in previous studies, but also other species, i.e. Tai Forest EBOV (TAFV), Sudan EBOV (SUDV), Bundibugyo EBOV (BDBV), and Reston EBOV (RESTV) and would bring the promising results as potent vaccine candidates.


Assuntos
Vacinas contra Ebola/imunologia , Ebolavirus/imunologia , Epitopos de Linfócito B/imunologia , Epitopos de Linfócito T/imunologia , Glicoproteínas/imunologia , Alelos , Sequência de Aminoácidos , Vacinas contra Ebola/genética , Ebolavirus/genética , Genes MHC Classe I , Genes MHC da Classe II , Glicoproteínas/química , Glicoproteínas/genética , Antígeno HLA-B7 , Imunogenicidade da Vacina , Simulação de Acoplamento Molecular , Estrutura Secundária de Proteína
16.
Microb Pathog ; 132: 275-281, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31078709

RESUMO

Toxoplasma gondii is an obligate intracellular parasite that causes one of the most common parasitic infections in humans and other warm-blooded animals. Currently, there are no effective treatments for inhibiting the formation of chronic tissue cysts in infected hosts. Thus, the development of a vaccine to protect against toxoplasmosis is an attractive option for avoiding infection. The aim of this study was to design an epitope-based vaccine for T. gondii. In the present study, an in silico approach was used to predict and analyze B-cell and T-cell epitopes and the transmembrane domain of proteins SAG1, MIC3, and ROP8. We also predicted the antigenicity, allergenicity, secondary and tertiary structures, and physicochemical characteristics of a chimeric protein. Next, codon optimization and mRNA structure prediction were conducted using bioinformatics tools, and the designed construct was chemically synthesized and cloned into the pET28a vector. SAG1 (amino acid positions 85-235), MIC3 (30-180), and ROP8 (85-185) were found to have several strong immunodominant epitopes that were joined with a rigid linker A(EAAAK)2A. Although the resultant protein called MRS (MIC3, ROP8, and SAG1) did not turn out to be an allergen, its antigenicity was estimated to be 0.7983. Additionally, MRS was selected as the best vaccine candidate on the basis of its secondary and tertiary structures. The number of amino acids, molecular weight, and numbers of negatively and positively charged residues of MRS were 427 and 45,661.31 Da, 45, and 50, respectively. ΔG of the best-predicted structure was -413.0 kcal/mol, and the first nucleotides at the 5' end did not form a stable hairpin or pseudoknot. Finally, successful expression and verification of the expressed MRS protein showed that in silico analysis was almost accurate. This vaccine candidate selected by in silico tools should be validated in experimental studies.


Assuntos
Antígenos de Protozoários/imunologia , Imunogenicidade da Vacina/imunologia , Vacinas Protozoárias/imunologia , Proteínas Recombinantes de Fusão/imunologia , Toxoplasma/imunologia , Sequência de Aminoácidos , Animais , Antígenos de Protozoários/genética , Biologia Computacional , Simulação por Computador , Epitopos de Linfócito B/imunologia , Epitopos de Linfócito T/imunologia , Expressão Gênica , Humanos , Modelos Moleculares , Conformação Proteica , Proteínas de Protozoários/genética , Proteínas de Protozoários/imunologia , RNA Mensageiro/química , Proteínas Recombinantes de Fusão/química , Proteínas Recombinantes de Fusão/genética , Toxoplasmose/imunologia , Toxoplasmose/prevenção & controle
17.
PLoS Med ; 16(4): e1002790, 2019 04.
Artigo em Inglês | MEDLINE | ID: mdl-31039172

RESUMO

BACKGROUND: There is an urgent need for an effective tuberculosis (TB) vaccine. Heterologous prime-boost regimens induce potent cellular immunity. MVA85A is a candidate TB vaccine. This phase I clinical trial was designed to evaluate whether alternating aerosol and intradermal vaccination routes would boost cellular immunity to the Mycobacterium tuberculosis antigen 85A (Ag85A). METHODS AND FINDINGS: Between December 2013 and January 2016, 36 bacille Calmette-Guérin-vaccinated, healthy UK adults were randomised equally between 3 groups to receive 2 MVA85A vaccinations 1 month apart using either heterologous (Group 1, aerosol-intradermal; Group 2, intradermal-aerosol) or homologous (Group 3, intradermal-intradermal) immunisation. Bronchoscopy and bronchoalveolar lavage (BAL) were performed 7 days post-vaccination. Adverse events (AEs) and peripheral blood were collected for 6 months post-vaccination. The laboratory and bronchoscopy teams were blinded to treatment allocation. One participant was withdrawn and was replaced. Participants were aged 21-42 years, and 28/37 were female. In a per protocol analysis, aerosol delivery of MVA85A as a priming immunisation was well tolerated and highly immunogenic. Most AEs were mild local injection site reactions following intradermal vaccination. Transient systemic AEs occurred following vaccination by both routes and were most frequently mild. All respiratory AEs following primary aerosol MVA85A (Group 1) were mild. Boosting an intradermal MVA85A prime with an aerosolised MVA85A boost 1 month later (Group 2) resulted in transient moderate/severe respiratory and systemic AEs. There were no serious adverse events and no bronchoscopy-related complications. Only the intradermal-aerosol vaccination regimen (Group 2) resulted in modest, significant boosting of the cell-mediated immune response to Ag85A (p = 0.027; 95% CI: 28 to 630 spot forming cells per 1 × 106 peripheral blood mononuclear cells). All 3 regimens induced systemic cellular immune responses to the modified vaccinia virus Ankara (MVA) vector. Serum antibodies to Ag85A and MVA were only induced after intradermal vaccination. Aerosolised MVA85A induced significantly higher levels of Ag85A lung mucosal CD4+ and CD8+ T cell cytokines compared to intradermal vaccination. Boosting with aerosol-inhaled MVA85A enhanced the intradermal primed responses in Group 2. The magnitude of BAL MVA-specific CD4+ T cell responses was lower than the Ag85A-specific responses. A limitation of the study is that while the intradermal-aerosol regimen induced the most potent cellular Ag85A immune responses, we did not boost the last 3 participants in this group because of the AE profile. Timing of bronchoscopies aimed to capture peak mucosal response; however, peak responses may have occurred outside of this time frame. CONCLUSIONS: To our knowledge, this is the first human randomised clinical trial to explore heterologous prime-boost regimes using aerosol and systemic routes of administration of a virally vectored vaccine. In this trial, the aerosol prime-intradermal boost regime was well tolerated, but intradermal prime-aerosol boost resulted in transient but significant respiratory AEs. Aerosol vaccination induced potent cellular Ag85A-specific mucosal and systemic immune responses. Whilst the implications of inducing potent mucosal and systemic immunity for protection are unclear, these findings are of relevance for the development of aerosolised vaccines for TB and other respiratory and mucosal pathogens. TRIAL REGISTRATION: ClinicalTrials.gov NCT01954563.


Assuntos
Aciltransferases/imunologia , Antígenos de Bactérias/imunologia , Vacinas contra a Tuberculose/administração & dosagem , Tuberculose/prevenção & controle , Administração por Inalação , Adulto , Aerossóis , Esquema de Medicação , Feminino , Vetores Genéticos/administração & dosagem , Vetores Genéticos/efeitos adversos , Humanos , Imunização Secundária , Imunogenicidade da Vacina , Injeções Intradérmicas , Masculino , Mycobacterium tuberculosis/imunologia , Método Simples-Cego , Tuberculose/imunologia , Vacinas contra a Tuberculose/efeitos adversos , Vacinas contra a Tuberculose/imunologia , Vacinação/efeitos adversos , Vacinas Sintéticas/administração & dosagem , Vacinas Sintéticas/efeitos adversos , Vacinas Sintéticas/imunologia , Adulto Jovem
18.
BMC Infect Dis ; 19(1): 453, 2019 May 22.
Artigo em Inglês | MEDLINE | ID: mdl-31117986

RESUMO

BACKGROUND: High hemagglutination inhibition (HAI) and neuraminidase inhibition (NAI) titers are generally associated with reduced influenza risk. While repeated influenza vaccination reduces seroresponse, vaccine effectiveness is not always reduced. METHODS: During the 2007-2008 influenza season, a randomized, placebo-controlled trial (FLUVACS) evaluated the efficacies of live-attenuated (LAIV) and inactivated influenza vaccines (IIV) among healthy adults aged 18-49 in Michigan; IIV vaccine efficacy (VE) and LAIV VE against influenza disease were estimated at 68% and 36%. Using the principal stratification/VE moderation framework, we analyzed data from this trial to assess how each VE varied by HAI or NAI responses to vaccination observed for vaccinated individuals and predicted counterfactually for placebo recipients. We also assessed how each VE varied with pre-vaccination/baseline variables including HAI titer, NAI titer, and vaccination history. RESULTS: IIV VE appeared to increase with Day 30 post-vaccination HAI titer, albeit not significantly (p=0.20 and estimated VE 14.4%, 70.5%, and 85.5% at titer below the assay lower quantification limit, 512, and 4096 (maximum)). Moreover, IIV VE increased significantly with Day 30 post-vaccination NAI titer (p=0.040), with estimated VE zero at titer 10 and 92.2% at highest titer 640. There was no evidence that fold-change in post-vaccination HAI or NAI titer associated with IIV VE (p=0.76, 0.38). For LAIV, there was no evidence that VE associated with post-vaccination or fold-rise HAI or NAI titers (p-values >0.40). For IIV, VE increased with increasing baseline NAI titer in those previously vaccinated, but VE decreased with increasing baseline NAI titer in those previously unvaccinated. In contrast, for LAIV, VE did not depend on previous vaccination or baseline HAI or NAI titer. CONCLUSIONS: Future efficacy trials should measure baseline and post-vaccination antibody titers in both vaccine and control/placebo recipients, enabling analyses to better elucidate correlates of vaccine- and natural-protection. TRIAL REGISTRATION: ClinicalTrials.gov NCT00538512. October 1, 2007.


Assuntos
Testes de Inibição da Hemaglutinação , Vacinas contra Influenza/uso terapêutico , Vacinas Atenuadas/uso terapêutico , Vacinas de Produtos Inativados/uso terapêutico , Adolescente , Adulto , Humanos , Imunogenicidade da Vacina , Testes Imunológicos , Vacinas contra Influenza/imunologia , Influenza Humana/prevenção & controle , Pessoa de Meia-Idade , Neuraminidase/antagonistas & inibidores , Placebos , Fatores de Tempo , Vacinas Atenuadas/imunologia , Vacinas de Produtos Inativados/imunologia
19.
Int J Infect Dis ; 85S: S26-S38, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31096055

RESUMO

OBJECTIVE: To demonstrate the potential of an MF59-adjuvanted inactivated trivalent seasonal influenza vaccine (aIIV3; Fluad™) to improve the immune response in young children, we review the immunogenicity, efficacy, and safety/tolerability of aIIV3 from a comprehensive clinical development program in a pediatric population with a specific need for improved influenza vaccines. METHODS: Data were analyzed from a series of 1 phase Ib, 3 phase II, and 2 phase III studies involving 11,942 children aged 6 months through 5years. RESULTS: The clinical data showed that aIIV3 had statistically significantly greater immunogenicity and efficacy in the prevention of influenza compared to conventional inactivated trivalent seasonal influenza vaccines (IIV3s). The safety profile of aIIV3 was generally similar to that of nonadjuvanted IIV3, apart from an increased frequency of solicited adverse events (AEs) following vaccination. The majority of solicited AEs were mild or moderate in severity and resolved within 1 to 3 days. CONCLUSIONS: aIIV3 was well tolerated, with immunogenicity and efficacy exceeding that of conventional IIV3 in children 6 months through 5years of age. The MF59-adjuvanted vaccine has the potential to fulfill an unmet clinical need in the prevention of seasonal influenza in this age group.


Assuntos
Adjuvantes Imunológicos , Vacinas contra Influenza/imunologia , Influenza Humana/prevenção & controle , Polissorbatos , Esqualeno , Adjuvantes Imunológicos/efeitos adversos , Pré-Escolar , Ensaios Clínicos como Assunto , Feminino , Humanos , Imunogenicidade da Vacina , Lactente , Vacinas contra Influenza/efeitos adversos , Masculino , Polissorbatos/efeitos adversos , Estações do Ano , Esqualeno/efeitos adversos , Vacinas de Produtos Inativados/imunologia
20.
Future Microbiol ; 14: 563-580, 2019 05.
Artigo em Inglês | MEDLINE | ID: mdl-31091978

RESUMO

Protection by meningococcal group A, C, W and Y (MenACWY) vaccines against four meningococcal disease-causing serogroups is increasingly important because of changing epidemiologic patterns of meningococcal disease, including recent meningococcal serogroup W outbreaks/disease clusters. The MenACWY vaccine conjugated to tetanus toxoid (MenACWY-TT) has been extensively evaluated across the age spectrum (age ≥6 weeks) in randomized Phase II and III and in postmarketing studies. Results support the robust immunogenicity of MenACWY-TT across ages and coadministration with other vaccines. The safety profile is similar regardless of age, primary versus booster vaccination, or concomitant administration; local (swelling, pain, redness) and systemic (fever, fatigue, headache, drowsiness, loss of appetite, irritability) reactogenicity events are most common. These data support use of MenACWY-TT to protect against MenACWY disease.


Assuntos
Infecções Meningocócicas/imunologia , Infecções Meningocócicas/prevenção & controle , Vacinas Meningocócicas/imunologia , Toxoide Tetânico/imunologia , Vacinas Conjugadas/imunologia , Antígenos de Bactérias/imunologia , Ensaios Clínicos Fase II como Assunto , Ensaios Clínicos Fase III como Assunto , Humanos , Imunogenicidade da Vacina , Vacinas Meningocócicas/administração & dosagem , Vacinas Meningocócicas/efeitos adversos , Neisseria meningitidis/patogenicidade , Ensaios Clínicos Controlados Aleatórios como Assunto , Sorogrupo , Vacinação , Vacinas Conjugadas/administração & dosagem , Vacinas Conjugadas/efeitos adversos
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