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1.
Sci Rep ; 11(1): 21844, 2021 11 04.
Artigo em Inglês | MEDLINE | ID: mdl-34737319

RESUMO

This study assesses attitudes towards COVID-19 vaccination and the predictive value of COVID-VAC, a novel scale, among adults in the four largest US metropolitan areas and nationally. A 36-item survey of 6037 Americans was conducted in mid-April 2021. The study reports factors for COVID-19 vaccine acceptance among: (1) already vaccinated; (2) unvaccinated but willing to accept a vaccine; and (3) unvaccinated and unwilling to vaccinate. More than 20% were unwilling to vaccinate, expressing concerns about vaccine efficacy and safety and questioning the disease's severity. Poverty, working outside of the home and conservative political views are predictors of unwillingness. Conversely, those who either personally tested positive for COVID-19, or had a family member who did so, were more likely to accept vaccination. Majorities of all respondents supported vaccination mandates for employees and university students. Respondents preferred to receive vaccines in their doctor´s office. Lower income and conservative ideology, but not race, were strongly associated with vaccine unwillingness. The predictive value of COVID-VAC was demonstrated. While vaccination mandates are likely to be accepted, additional effective, targeted interventions to increase vaccine uptake are needed urgently.


Assuntos
COVID-19/psicologia , Recusa de Vacinação/psicologia , Recusa de Vacinação/tendências , Adulto , Atitude , Vacinas contra COVID-19/administração & dosagem , Vacinas contra COVID-19/provisão & distribuição , Feminino , Fidelidade a Diretrizes/tendências , Política de Saúde/tendências , Humanos , Intenção , Masculino , Pessoa de Meia-Idade , SARS-CoV-2/patogenicidade , Inquéritos e Questionários , Estados Unidos , Vacinação/psicologia , Vacinação/tendências , Vacinas/farmacologia
2.
PLoS One ; 16(10): e0259059, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34710168

RESUMO

As safe and effective vaccines become widely available, attaining herd immunity and limiting the spread of COVID-19 will depend on individuals choosing to vaccinate-and doing so quickly enough to outpace mutations. Using online surveys conducted across six Latin American countries in January 2021, we experimentally assess messages designed to counteract informational deficiencies and collective action problems that may drive hesitancy. We first find that basic vaccine information persuades around 8% of hesitant individuals to become willing to vaccinate, reduces intended wait to vaccinate by 0.4 months, and increases willingness to encourage others to vaccinate. Rather than facilitating free riding, learning, or social conformity, additional information about others' behavior increases vaccine acceptance when respondents expect herd immunity will be achieved. Finally, priming the social approval benefits of vaccinating also increases vaccine acceptance. These results suggest that providing information and shaping social expectations and incentives could both significantly increase vaccine uptake.


Assuntos
COVID-19/psicologia , Recusa de Vacinação/psicologia , Vacinação/psicologia , COVID-19/prevenção & controle , Vacinas contra COVID-19/uso terapêutico , Conhecimentos, Atitudes e Prática em Saúde , Humanos , América Latina , Aceitação pelo Paciente de Cuidados de Saúde/psicologia , Aceitação pelo Paciente de Cuidados de Saúde/estatística & dados numéricos , Comunicação Persuasiva , SARS-CoV-2/patogenicidade , Inquéritos e Questionários , Vacinação/estatística & dados numéricos , Recusa de Vacinação/tendências , Vacinas/farmacologia
4.
PLoS One ; 16(8): e0254605, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34398875

RESUMO

The re-emergence of virulent strains of the Infectious Bursal Disease Virus (IBDV) leads to significant economic losses of poultry industry in Pakistan during last few years. This disease causes the infection of bursa, which leads to major immune losses. A total number of 30 samples from five IBD outbreaks during the period of 2019-20 were collected from different areas of Faisalabad district, Pakistan and assayed by targeting the IBD virus VP2 region through RT-PCR. Among all the outbreaks, almost 80% of poultry birds were found positive for the IBDV. The bursa tissues were collected from the infected birds and histopathological examination of samples revealed severe lymphocytic depletion, infiltration of inflammatory cells, and necrosis of the bursa of Fabricius (BF). Positive samples were subjected to re-isolation and molecular characterization of IBDV. The Pakistan IBDV genes were subjected to DNA sequencing to determine the virus nucleotide sequences. The sequences of 100 Serotype-I IBDVs showing nearest homology were compared and identified with the study sequence. The construction of the phylogenetic tree for nucleotide sequences was accomplished by the neighbor-joining method in MEGA-6 with reference strains. The VP2 segment reassortment of IBDVs carrying segment A were identified as one important type of circulating strains in Pakistan. The findings indicated the molecular features of the Pakistan IBDV strains playing a role in the evolution of new strains of the virus, which will contribute to the vaccine selection and effective prevention of the disease.


Assuntos
Infecções por Birnaviridae/epidemiologia , Vírus da Doença Infecciosa da Bursa/patogenicidade , Aves Domésticas/virologia , Vacinas/farmacologia , Animais , Infecções por Birnaviridae/veterinária , Infecções por Birnaviridae/virologia , Bolsa de Fabricius/patologia , Bolsa de Fabricius/virologia , Galinhas/virologia , Surtos de Doenças/veterinária , Humanos , Vírus da Doença Infecciosa da Bursa/genética , Paquistão/epidemiologia , Filogenia , Doenças das Aves Domésticas/virologia , Proteínas Estruturais Virais/genética , Proteínas Estruturais Virais/imunologia
5.
Malays J Pathol ; 43(2): 203-217, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-34448786

RESUMO

The coronavirus disease 2019 (COVID-19) is one of the biggest public health threats in the 21st century. Nearly every country in the world has been affected by COVID-19. The magnitude of the problem, with over 179 million confirmed cases and 3.8 million deaths worldwide, has driven researchers to search for vaccines to combat the disease. The discovery and development of a new vaccine, from the initial stage to the vaccine finally reaching the patients, usually take many years. However, given the urgency of the situation, many clinical trials on the COVID-19 vaccines have been conducted at extraordinary speed, whereas several vaccines against SARS-CoV-2 are being administered worldwide. This article gives an overview of the different types of COVID-19 vaccines, with a focus on those with promising results and are commonly used worldwide. It also gives an overview of herd immunity and discusses the challenges in achieving herd immunity through the global vaccination campaigns. Last but not least, some strategies that may be used to address these challenges are discussed.


Assuntos
Vacinas contra COVID-19/imunologia , COVID-19/imunologia , Imunidade Coletiva/imunologia , Saúde Pública/estatística & dados numéricos , Vacinas/imunologia , Humanos , SARS-CoV-2/imunologia , SARS-CoV-2/patogenicidade , Vacinas/farmacologia
6.
Sci Rep ; 11(1): 15431, 2021 07 29.
Artigo em Inglês | MEDLINE | ID: mdl-34326355

RESUMO

Currently, no approved vaccine is available against the Middle East respiratory syndrome coronavirus (MERS-CoV), which causes severe respiratory disease. The spike glycoprotein is typically considered a suitable target for MERS-CoV vaccine candidates. A computational strategy can be used to design an antigenic vaccine against a pathogen. Therefore, we used immunoinformatics and computational approaches to design a multi-epitope vaccine that targets the spike glycoprotein of MERS-CoV. After using numerous immunoinformatics tools and applying several immune filters, a poly-epitope vaccine was constructed comprising cytotoxic T-cell lymphocyte (CTL)-, helper T-cell lymphocyte (HTL)-, and interferon-gamma (IFN-γ)-inducing epitopes. In addition, various physicochemical, allergenic, and antigenic profiles were evaluated to confirm the immunogenicity and safety of the vaccine. Molecular interactions, binding affinities, and the thermodynamic stability of the vaccine were examined through molecular docking and dynamic simulation approaches, during which we identified a stable and strong interaction with Toll-like receptors (TLRs). In silico immune simulations were performed to assess the immune-response triggering capabilities of the vaccine. This computational analysis suggested that the proposed vaccine candidate would be structurally stable and capable of generating an effective immune response to combat viral infections; however, experimental evaluations remain necessary to verify the exact safety and immunogenicity profile of this vaccine.


Assuntos
Epitopos/imunologia , Coronavírus da Síndrome Respiratória do Oriente Médio/imunologia , Vacinas/imunologia , Biologia Computacional , Infecções por Coronavirus/imunologia , Infecções por Coronavirus/prevenção & controle , Epitopos de Linfócito B/genética , Epitopos de Linfócito B/imunologia , Epitopos de Linfócito T/genética , Epitopos de Linfócito T/imunologia , Humanos , Imunogenicidade da Vacina/imunologia , Coronavírus da Síndrome Respiratória do Oriente Médio/genética , Coronavírus da Síndrome Respiratória do Oriente Médio/patogenicidade , Modelos Moleculares , Simulação de Acoplamento Molecular , Filogenia , Ligação Proteica , Glicoproteína da Espícula de Coronavírus/imunologia , Linfócitos T Citotóxicos/imunologia , Linfócitos T Auxiliares-Indutores/imunologia , Vacinas/farmacologia , Vacinas de DNA , Vacinas de Subunidades/imunologia , Vacinas Virais/imunologia
7.
Sci Rep ; 11(1): 11472, 2021 06 01.
Artigo em Inglês | MEDLINE | ID: mdl-34075153

RESUMO

In post-stroke patients, a decreased adherence to antiplatelet drugs is a major challenge in the prevention of recurrent stroke. Previously, we reported an antiplatelet vaccine against S100A9 in mice, but the use of Freund's adjuvant and the difference in amino acid sequences in epitopes between mice and humans were problematic for clinical use. Here, we redesigned the S100A9 vaccine for the common sequence in both humans and monkeys and examined its effects in cynomolgus monkeys with Alum adjuvant. First, we assessed several candidate epitopes and selected 102 to 112 amino acids as the suitable epitope, which could produce antibodies. When this peptide vaccine was intradermally injected into 4 cynomolgus monkeys with Alum, the antibody against human S100A9 was successfully produced. Anti-thrombotic effects were shown in two monkeys in a mixture of vaccinated serum and fresh whole blood from another cynomolgus monkey. Additionally, the anti-thrombotic effects were partially inhibited by the epitope peptide, indicating the feasibility of neutralizing anti-thrombotic effects of produced antibodies. Prolongation of bleeding time was not observed in vaccinated monkeys. Although further studies on increasing the effect of vaccine and safety are necessary, this vaccine will be a promising approach to improve adherence to antiplatelet drugs in clinical settings.


Assuntos
Calgranulina B , Fibrinolíticos , Peptídeos , Trombose , Vacinas , Animais , Calgranulina B/química , Calgranulina B/imunologia , Calgranulina B/farmacologia , Fibrinolíticos/imunologia , Fibrinolíticos/farmacologia , Humanos , Macaca fascicularis , Macaca mulatta , Peptídeos/química , Peptídeos/imunologia , Peptídeos/farmacologia , Trombose/imunologia , Trombose/terapia , Vacinas/imunologia , Vacinas/farmacologia
8.
Biomed Res Int ; 2021: 8845826, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34095312

RESUMO

Immunotherapy, a treatment based on host immune system activation, has been shown to provide a substitute for marginally effective conventional chemotherapy in controlling visceral leishmaniasis (VL), the deadliest form of leishmaniasis. As the majority of endemic inhabitants exhibit either subclinical or asymptomatic infection which often develops into the active disease state, therapeutic intervention seems to be an important avenue for combating infections by stimulating the natural defense system of infected individuals. With this perspective, the present study focuses on two immunodominant Leishmania (L.) donovani antigens (triosephosphate isomerase and enolase) previously proved to be potent prophylactic VL vaccine candidates, for generating a recombinant chimeric antigen. This is based on the premise that in a heterogeneous population, a multivalent antigen vaccine would be required for an effective response against leishmaniasis (a complex parasitic disease). The resulting molecule rLdT-E chimeric protein was evaluated for its immunogenicity and immunotherapeutic efficacy. A Th1 stimulating adjuvant BCG was employed with the protein which showed a remarkable 70% inhibition of splenic parasitic multiplication positively correlated with boosted Th1 dominant immune response against lethal L. donovani challenge in hamsters as evidenced by high IFN-γ and TNF-α and low IL-10. In addition, immunological analysis of antibody subclass presented IgG2-based humoral response besides considerable delayed-type hypersensitivity and lymphocyte proliferative responses in rLdT-E/BCG-treated animals. Our observations indicate the potential of the chimera towards its candidature for an effective vaccine against Leishmania donovani infection.


Assuntos
Leishmania donovani/genética , Leishmaniose Visceral/terapia , Células Th1/imunologia , Imunidade Adaptativa/imunologia , Animais , Antígenos de Protozoários/imunologia , Quimera , Cricetinae , Citocinas/metabolismo , Feminino , Fatores Imunológicos/metabolismo , Imunoterapia/métodos , Leishmania donovani/imunologia , Leishmania donovani/patogenicidade , Leishmaniose Visceral/imunologia , Leishmaniose Visceral/metabolismo , Leucócitos Mononucleares/metabolismo , Ativação Linfocitária/imunologia , Linfócitos/metabolismo , Fosfopiruvato Hidratase/imunologia , Proteínas de Protozoários/metabolismo , Proteínas Recombinantes/metabolismo , Triose-Fosfato Isomerase/imunologia , Vacinas/farmacologia
9.
PLoS One ; 16(6): e0253810, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34166453

RESUMO

Maternal nutrition during gestation can cause epigenetic effects that translate to alterations in gene expression in offspring. This 2-year study employed RNA-sequencing technology to evaluate the pre- and post-vaccination muscle transcriptome of early-weaned Bos indicus-influenced beef calves born from dams offered different supplementation strategies from 57 ± 5 d prepartum until 17 ± 5 d postpartum. Seventy-two Brangus heifers (36 heifers/yr) were stratified by body weight and body condition score and assigned to bahiagrass pastures (3 heifers/pasture/yr). Treatments were randomly assigned to pastures and consisted of (i) no pre- or postpartum supplementation (NOSUP), (ii) pre- and postpartum supplementation of protein and energy using 7.2 kg of dry matter/heifer/wk of molasses + urea (MOL), or (iii) MOL fortified with 105 g/heifer/wk of methionine hydroxy analog (MOLMET). Calves were weaned on d 147 of the study. On d 154, 24 calves/yr (8 calves/treatment) were randomly selected and individually limit-fed a high-concentrate diet until d 201. Calves were vaccinated on d 160. Muscle biopsies were collected from the same calves (4 calves/treatment/day/yr) on d 154 (pre-vaccination) and 201 (post-vaccination) for gene expression analysis using RNA sequencing. Molasses maternal supplementation led to a downregulation of genes associated with muscle cell differentiation and development along with intracellular signaling pathways (e.g., Wnt and TGF-ß signaling pathway) compared to no maternal supplementation. Maternal fortification with methionine altered functional gene-sets involved in amino acid transport and metabolism and the one-carbon cycle. In addition, muscle transcriptome was impacted by vaccination with a total of 2,396 differentially expressed genes (FDR ≤ 0.05) on d 201 vs. d 154. Genes involved in cell cycle progression, extracellular matrix, and collagen formation were upregulated after vaccination. This study demonstrated that maternal supplementation of energy and protein, with or without, methionine has long-term implications on the muscle transcriptome of offspring and potentially influence postnatal muscle development.


Assuntos
Ração Animal , Suplementos Nutricionais , Epigênese Genética , Metionina , Músculo Esquelético , Efeitos Tardios da Exposição Pré-Natal , Vacinas/farmacologia , Via de Sinalização Wnt , Animais , Bovinos , Epigênese Genética/efeitos dos fármacos , Epigênese Genética/imunologia , Feminino , Masculino , Metionina/deficiência , Metionina/farmacologia , Músculo Esquelético/imunologia , Músculo Esquelético/metabolismo , Gravidez , Efeitos Tardios da Exposição Pré-Natal/imunologia , Efeitos Tardios da Exposição Pré-Natal/metabolismo , Transcriptoma , Vacinas/imunologia , Via de Sinalização Wnt/efeitos dos fármacos , Via de Sinalização Wnt/imunologia
10.
Hematol Oncol ; 39(4): 448-464, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-33963789

RESUMO

Autologous cell vaccines use a patient's tumor cells to stimulate a broad antitumor response in vivo. This approach shows promise for treating hematologic cancers in early phase clinical trials, but overall safety and efficacy remain poorly described. We conducted a systematic review assessing the use of autologous cell vaccination in treating hematologic cancers. Primary outcomes of interest were safety and clinical response, with secondary outcomes including survival, relapse rate, correlative immune assays and health-quality related metrics. We performed a search of MEDLINE, Embase and the Cochrane Register of Controlled Trials including any interventional trial employing an autologous, whole cell product in any hematologic malignancy. Risk of bias was assessed using a modified Institute of Health Economics tool. Across 20 single arm studies, only 341 of 592 enrolled participants received one or more vaccinations. Primary reasons for not receiving vaccination included rapid disease progression/death and manufacturing challenges. Overall, few high-grade adverse events were observed. One death was reported and attributed to a GM-CSF producing allogeneic cell line co-administered with the autologous vaccine. Of 58 evaluable patients, the complete response rate was 21.0% [95% CI, 10.4%-37.8%)] and overall response rate was 35.8% (95% CI, 24.4%-49.0%). Of 97 evaluable patients for survival, the 5-years overall survival rate was 64.9% (95% CI, 52.6%-77.2%) and disease-free survival was 59.7% (95% CI, 47.7%-71.7%). We conclude that, in hematologic malignancies, based on limited available data, autologous cell vaccines are safe and display a trend towards efficacy but that challenges exist in vaccine manufacture and administration.


Assuntos
Neoplasias Hematológicas/terapia , Vacinas/uso terapêutico , Adulto , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Vacinas/farmacologia
11.
Ticks Tick Borne Dis ; 12(5): 101738, 2021 09.
Artigo em Inglês | MEDLINE | ID: mdl-34023540

RESUMO

Ticks and tick-borne diseases (TBD) represent a challenge for human and animal health worldwide. Climate change, distribution of tick hosts, and ecological and anthropogenically-induced changes contribute to the geographic expansion of ticks and tick-borne pathogens. Traditional control methods are based on the use of acaricides to reduce tick infestations, but vaccines represent a more effective, sustainable and environmentally sound approach for the control of ticks and TBD. Recent application of omics technologies to the study of the mechanisms involved in tick-host-pathogen interactions have advanced the characterization of molecular mechanisms involved in TBD and the identification of candidate vaccine protective antigens. However, as discussed in this opinion paper, translational biotechnology may translate into novel interventions required to advance in addressing the challenge that ticks and TBD represent for world health and economy.


Assuntos
Biotecnologia/métodos , Doenças Transmitidas por Carrapatos , Carrapatos , Vacinas , Acaricidas/farmacologia , Animais , Interações Hospedeiro-Patógeno , Humanos , Proteômica/métodos , Controle de Ácaros e Carrapatos/métodos , Infestações por Carrapato/tratamento farmacológico , Infestações por Carrapato/prevenção & controle , Doenças Transmitidas por Carrapatos/tratamento farmacológico , Doenças Transmitidas por Carrapatos/prevenção & controle , Carrapatos/efeitos dos fármacos , Carrapatos/imunologia , Vacinas/imunologia , Vacinas/farmacologia
12.
Molecules ; 26(9)2021 Apr 24.
Artigo em Inglês | MEDLINE | ID: mdl-33923304

RESUMO

Chitosan is a non-toxic biological material, but chitosan is insoluble in water, which hinders the development and utilization of chitosan. Chitosan derivatives N-2-Hydroxypropyl trimethyl ammonium chloride (N-2-HACC) and carboxymethyl chitosan (CMCS) with good water solubility were synthesized by our laboratory. In this study, we synthesized mesoporous SiO2 nanoparticles by the emulsion, and then the mesoporous SiO2 nanoparticles were modified with γ-aminopropyltriethoxysilane to synthesize aminated mesoporous SiO2 nanoparticles; CMCS and N-2-HACC was used to cross-link the aminated mesoporous SiO2 nanoparticles to construct SiO2@CMCS-N-2-HACC nanoparticles. Because the aminated mesoporous SiO2 nanoparticles with positively charged can react with the mucous membranes, the virus enters the body mainly through mucous membranes, so Newcastle disease virus (NDV) was selected as the model drug to evaluate the performance of the SiO2@CMCS-N-2-HACC nanoparticles. We prepared the SiO2@CMCS-N-2-HACC nanoparticles loaded with inactivated NDV (NDV/SiO2@CMCS-N-2-HACC). The SiO2@CMCS-N-2-HACC nanoparticles as delivery carrier had high loading capacity, low cytotoxicity, good acid resistance and bile resistance and enteric solubility, and the structure of NDV protein encapsulated in the nano vaccine was not destroyed. In addition, the SiO2@CMCS-N-2-HACC nanoparticles could sustain slowly released NDV. Therefore, the SiO2@CMCS-N-2-HACC nanoparticles have the potential to be served as delivery vehicle for vaccine and/or drug.


Assuntos
Quitosana/farmacologia , Sistemas de Liberação de Medicamentos , Nanopartículas/química , Doença de Newcastle/tratamento farmacológico , Animais , Proliferação de Células/efeitos dos fármacos , Quitosana/análogos & derivados , Humanos , Nanopartículas/uso terapêutico , Doença de Newcastle/patologia , Doença de Newcastle/virologia , Vírus da Doença de Newcastle/efeitos dos fármacos , Vírus da Doença de Newcastle/patogenicidade , Dióxido de Silício/química , Vacinas/química , Vacinas/farmacologia , Água/química
13.
PLoS One ; 16(4): e0250797, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33909687

RESUMO

BACKGROUND: The accelerated vaccine development in response to the COVID-19 pandemic should lead to a vaccine being available early 2021, albeit in limited supply and possibly without full vaccine acceptance. We assessed the short-term impact of a COVID-19 immunization program with varying constraints on population health and non-pharmaceutical interventions (NPIs) needs. METHODS: A SARS-CoV-2 transmission model was calibrated to French epidemiological data. We defined several vaccine implementation scenarios starting in January 2021 based on timing of discontinuation of NPIs, supply and uptake constraints, and their relaxation. We assessed the number of COVID-19 hospitalizations averted, the need for and number of days with NPIs in place over the 2021-2022 period. RESULTS: An immunisation program under constraints could reduce the burden of COVID-19 hospitalizations by 9-40% if the vaccine prevents against infections. Relaxation of constraints not only reduces further COVID-19 hospitalizations (30-39% incremental reduction), it also allows for NPIs to be discontinued post-2021 (0 days with NPIs in 2022 versus 11 to 125 days for vaccination programs under constraints and 327 in the absence of vaccination). CONCLUSION: For 2021, COVID-19 control is expected to rely on a combination of NPIs and the outcome of early immunisation programs. The ability to overcome supply and uptake constraints will help prevent the need for further NPIs post-2021. As the programs expand, efficiency assessments will be needed to ensure optimisation of control policies post-emergency use.


Assuntos
Vacinas contra COVID-19/farmacologia , COVID-19/imunologia , Vacinação/tendências , França/epidemiologia , Humanos , Programas de Imunização , Modelos Teóricos , Pandemias/prevenção & controle , SARS-CoV-2/patogenicidade , Vacinas/farmacologia
14.
Bioorg Chem ; 111: 104838, 2021 06.
Artigo em Inglês | MEDLINE | ID: mdl-33848722

RESUMO

A focused library of water soluble 1,2,3-triazole tethered glycopeptide conjugates derived from variety of azido-monosaccharides and aliphatic azido-alcohols were synthesized through manipulation at the C-terminus of Pam3CAG and screened for their potential as TLR2 agonistic adjuvants against HBsAg antigen. In vitro ligand induced TLR2 signal activation was observed with all the analogues upon treatment with HEK blue TLR2 cell lines. Conjugate derived from ribose (6e), which exhibited pronounced HBsAg specific antibody (IgG) titer also shown enhanced CD8+ population indicating superior cell mediated immunity compared to standard adjuvant Pam3CSK4. Further, docking studies revealed ligand induced heterodimerization between TLR1 and 2. Overall, the result indicates the usefulness of novel conjugates as potential vaccine adjuvant.


Assuntos
Adjuvantes Imunológicos/farmacologia , Receptor 2 Toll-Like/agonistas , Triazóis/farmacologia , Vacinas/farmacologia , Adjuvantes Imunológicos/química , Linhagem Celular , Relação Dose-Resposta a Droga , Humanos , Imunidade Celular/efeitos dos fármacos , Estrutura Molecular , Relação Estrutura-Atividade , Triazóis/química , Vacinas/química
15.
J Nanobiotechnology ; 19(1): 69, 2021 Mar 05.
Artigo em Inglês | MEDLINE | ID: mdl-33673858

RESUMO

BACKGROUND: Escherichia coli K1 (E. coli K1) caused neonatal meningitis remains a problem, which rises the urgent need for an effective vaccine. Previously, we rationally designed and produced the recombinant protein OmpAVac (Vo), which elicited protective immunity against E. coli K1 infection. However, Vo has limited stability, which hinders its future industrial application. METHOD: Chitosan-modified poly (lactic-co-glycolic acid) (PLGA) nanoparticles were prepared and used as carried for the recombinant Vo. And the safety, stability and immunogenicity of Vo delivered by chitosan-modified PLGA nanoparticles were tested in vitro and in a mouse model of bacteremia. RESULTS: We successfully generated chitosan-modified PLGA nanoparticles for the delivery of recombinant Vo (VoNP). In addition, we found that a freeze-drying procedure increases the stability of the VoNPs without changing the shape, size distribution and encapsulation of the Vo protein. Unlike aluminum adjuvant, the nanoparticles that delivered Vo were immunoprotective in mice even after storage for as long as 180 days. CONCLUSIONS: We identified an effective strategy to improve the stability of Vo to maintain its immunogenicity, which will contribute to the future development of vaccines against E. coli K1.


Assuntos
Quitosana/química , Infecções por Escherichia coli/prevenção & controle , Escherichia coli , Meningite/prevenção & controle , Nanopartículas/química , Vacinas/química , Vacinas/farmacologia , Adjuvantes Imunológicos , Animais , Modelos Animais de Doenças , Sistemas de Liberação de Medicamentos/métodos , Infecções por Escherichia coli/patologia , Feminino , Imunidade , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Nus , Proteínas Recombinantes
16.
Sci Rep ; 11(1): 6315, 2021 03 18.
Artigo em Inglês | MEDLINE | ID: mdl-33737699

RESUMO

There is a high interest on gut health in poultry with special focus on consequences of the intestinal diseases, such as coccidiosis and C. perfringens-induced necrotic enteritis (NE). We developed a custom gene expression panel, which could provide a snapshot of gene expression variation under challenging conditions. Ileum gene expression studies were performed through high throughput reverse transcription quantitative real-time polymerase chain reaction. A deep review on the bibliography was done and genes related to intestinal health were selected for barrier function, immune response, oxidation, digestive hormones, nutrient transport, and metabolism. The panel was firstly tested by using a nutritional/Clostridium perfringens model of intestinal barrier failure (induced using commercial reused litter and wheat-based diets without exogenous supplementation of enzymes) and the consistency of results was evaluated by another experiment under a coccidiosis challenge (orally gavaged with a commercial coccidiosis vaccine, 90× vaccine dose). Growth traits and intestinal morphological analysis were performed to check the gut barrier failure occurrence. Results of ileum gene expression showed a higher expression in genes involved in barrier function and nutrient transport in chickens raised in healthy conditions, while genes involved in immune response presented higher expression in C.perfringens-challenged birds. On the other hand, the Eimeria challenge also altered the expression of genes related to barrier function and metabolism, and increased the expression of genes related to immune response and oxidative stress. The panel developed in the current study gives us an overview of genes and pathways involved in broiler response to pathogen challenge. It also allows us to deep into the study of differences in gene expression pattern and magnitude of responses under either a coccidial vaccine or a NE.


Assuntos
Galinhas/microbiologia , Infecções por Clostridium/microbiologia , Enterite/microbiologia , Doenças das Aves Domésticas/microbiologia , Ração Animal/microbiologia , Animais , Infecções por Clostridium/genética , Clostridium perfringens/efeitos dos fármacos , Clostridium perfringens/patogenicidade , Coccidiose/genética , Coccidiose/microbiologia , Coccidiose/prevenção & controle , Suplementos Nutricionais , Eimeria/efeitos dos fármacos , Eimeria/patogenicidade , Enterite/genética , Enterite/prevenção & controle , Expressão Gênica/efeitos dos fármacos , Humanos , Doenças das Aves Domésticas/genética , Doenças das Aves Domésticas/prevenção & controle , Vacinas/farmacologia
17.
BMC Pregnancy Childbirth ; 21(1): 217, 2021 Mar 17.
Artigo em Inglês | MEDLINE | ID: mdl-33731029

RESUMO

BACKGROUND: Most post-licensure vaccine pharmacovigilance in low- and middle-income countries (LMICs) are passive reporting systems. These have limited utility for maternal immunization pharmacovigilance in LMIC settings and need to be supplemented with active surveillance. Our study's main objective was to identify existing perinatal data collection systems in LMICs that collect individual information on maternal and neonatal health outcomes and could be developed to inform active safety surveillance of novel vaccines for use during pregnancy. METHODS: A scoping review was performed following the Arksey and O'Malley six-stage approach. We included studies describing electronic or mixed paper-electronic data collection systems in LMICs, including research networks, electronic medical records, and custom software platforms for health information systems. Medline PubMed, EMBASE, Global Health, Cochrane Library, LILACS, Bibliography of Asian Studies (BAS), and CINAHL were searched through August 2019. We also searched grey literature including through Google and websites of existing relevant perinatal data collection systems, as well as contacted authors of key studies and experts in the field to validate the information and identify additional sources of relevant unpublished information. RESULTS: A total of 11,817 records were identified. The full texts of 264 records describing 96 data collection systems were assessed for eligibility. Eight perinatal data collection systems met our inclusion criteria: Global Network's Maternal Newborn Health Registry, International Network for the Demographic Evaluation of Populations and their Health; Perinatal Informatic System; Pregnancy Exposure Registry & Birth Defects Surveillance; SmartCare; Open Medical Record System; Open Smart Register Platform and District Health Information Software 2. These selected systems were qualitatively characterized according to seven different domains: governance; system design; system management; data management; data sources, outcomes and data quality. CONCLUSION: This review provides a list of active maternal and neonatal data collection systems in LMICs and their characteristics as well as their outreach, strengths, and limitations. Findings could potentially help further understand where to obtain population-based high-quality information on outcomes to inform the conduct of maternal immunization active vaccine safety surveillance activities and research in LMICs.


Assuntos
Sistemas de Informação em Saúde , Saúde do Lactente , Saúde Materna , Vigilância de Produtos Comercializados , Vacinas/farmacologia , Coleta de Dados/métodos , Países em Desenvolvimento , Feminino , Sistemas de Informação em Saúde/organização & administração , Sistemas de Informação em Saúde/normas , Humanos , Fatores Imunológicos/farmacologia , Recém-Nascido , Farmacovigilância , Gravidez , Vigilância de Produtos Comercializados/métodos , Vigilância de Produtos Comercializados/estatística & dados numéricos , Vacinação/métodos , Vacinação/normas
20.
Methods Mol Biol ; 2244: 403-463, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33555597

RESUMO

Human cytomegalovirus is the largest human herpesvirus and shares many core features of other herpesviruses such as tightly regulated gene expression during genome replication and latency as well as the establishment of lifelong persistence following infection. In contrast to stereotypic clinical syndromes associated with alpha-herpesvirus infections, almost all primary HCMV infections are asymptomatic and acquired early in life in most populations in the world. Although asymptomatic in most individuals, HCMV is a major cause of disease in hosts with deficits in adaptive and innate immunity such as infants who are infected in utero and allograft recipients following transplantation. Congenital HCMV is a commonly acquired infection in the developing fetus that can result in a number of neurodevelopmental abnormalities. Similarly, HCMV is a major cause of disease in allograft recipients in the immediate and late posttransplant period and is thought to be a major contributor to chronic allograft rejection. Even though HCMV induces robust innate and adaptive immune responses, it also encodes a vast array of immune evasion functions that are thought aid in its persistence. Immune correlates of protective immunity that prevent or modify intrauterine HCMV infection remain incompletely defined but are thought to consist primarily of adaptive responses in the pregnant mother, thus making congenital HCMV a potentially vaccine modifiable disease. Similarly, HCMV infection in allograft recipients is often more severe in recipients without preexisting adaptive immunity to HCMV. Thus, there has been a considerable effort to modify HCMV specific immunity in transplant recipient either through active immunization or passive transfer of adaptive effector functions. Although efforts to develop an efficacious vaccine and/or passive immunotherapy to limit HCMV disease have been underway for nearly six decades, most have met with limited success at best. In contrast to previous efforts, current HCMV vaccine development has relied on observations of unique properties of HCMV in hopes of reproducing immune responses that at a minimum will be similar to that following natural infection. However, more recent findings have suggested that immunity following naturally acquired HCMV infection may have limited protective activity and almost certainly, is not sterilizing. Such observations suggest that either the induction of natural immunity must be specifically tailored to generate protective activity or alternatively, that providing targeted passive immunity to susceptible populations could be prove to be more efficacious.


Assuntos
Vacinas contra Citomegalovirus/imunologia , Citomegalovirus/imunologia , Vacinação/métodos , Imunidade Adaptativa/imunologia , Anticorpos Antivirais/imunologia , Citomegalovirus/genética , Infecções por Citomegalovirus/imunologia , Infecções por Citomegalovirus/prevenção & controle , Suscetibilidade a Doenças , Feminino , Humanos , Imunidade Humoral/imunologia , Imunidade Inata/imunologia , Lactente , Masculino , Gravidez , Vacinas/imunologia , Vacinas/metabolismo , Vacinas/farmacologia
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