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1.
Arch Virol ; 166(11): 2975-2988, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-34524535

RESUMO

Porcine deltacoronavirus (PDCoV) is one of the most important enteropathogenic pathogens, and it causes enormous economic losses to the global commercial pork industry. PDCoV was initially reported in Hong Kong (China) in 2012 and subsequently emerged in swine herds with diarrhea in Ohio (USA) in 2014. Since then, it has spread to Canada, South Korea, mainland China, and several Southeast Asian countries. Information about the epidemiology, evolution, prevention, and control of PDCoV and its prevalence in China has not been comprehensively reported, especially in the last five years. This review is an update of current information on the general characteristics, epidemiology, geographical distribution, and evolutionary relationships, and the status of PDCoV vaccine development, focusing on the prevalence of PDCoV in China and vaccine research in particular. Together, this information will provide us with a greater understanding of PDCoV infection and will be helpful for establishing new strategies for controlling this virus worldwide.


Assuntos
Infecções por Coronavirus/veterinária , Deltacoronavirus/genética , Deltacoronavirus/patogenicidade , Doenças dos Suínos/epidemiologia , Vacinas Virais/farmacologia , Animais , Evolução Biológica , China/epidemiologia , Infecções por Coronavirus/epidemiologia , Infecções por Coronavirus/transmissão , Infecções por Coronavirus/virologia , Especificidade de Hospedeiro , Filogenia , Prevalência , Suínos , Doenças dos Suínos/transmissão , Doenças dos Suínos/virologia
2.
J Fish Dis ; 44(12): 1911-1924, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34402092

RESUMO

Pancreas disease (PD) caused by salmonid alphavirus (SAV) continues to negatively impact salmon farming. To assess the effect on growth and mortality of three vaccines against PD, two controlled field designs were employed: one controlled field study with individual marked fish (PIT tag) assessing three PD vaccines and three controls groups, and a second controlled field study with group marked fish (Maxilla) comparing two PD vaccines against controls. In addition, a descriptive study using whole cages compared fish immunized with two different PD vaccines against controls. The target populations experienced a natural PD outbreak where both SAV 2 and SAV 3 were identified. Only one of the PD vaccines provided statistically significant improvements in harvest weight of 0.43 kg (CI: 0.29-0.57) and 0.51 kg (CI: 0.36-0.65) compared with the control in the PIT tag and the Maxilla study, respectively. In the latter, a significant reduction in mortality of 1.31 (CI:0.8-1.8) per cent points was registered for the same vaccine compared with controls. These results aligned with the growth and PD-specific mortality registered in the descriptive Cage study. The data in this study show a difference in the efficacy of PD vaccines in farmed Atlantic salmon.


Assuntos
Infecções por Alphavirus/veterinária , Doenças dos Peixes/virologia , Pancreatopatias/veterinária , Vacinas Virais/farmacologia , Alphavirus/efeitos dos fármacos , Infecções por Alphavirus/imunologia , Infecções por Alphavirus/prevenção & controle , Animais , Aquicultura , Doenças dos Peixes/imunologia , Doenças dos Peixes/prevenção & controle , Pancreatopatias/prevenção & controle , Pancreatopatias/virologia , Salmo salar , Vacinas de Produtos Inativados/farmacologia
3.
Vet Res ; 52(1): 98, 2021 Jun 30.
Artigo em Inglês | MEDLINE | ID: mdl-34193256

RESUMO

Flaviviruses are enveloped single positive-stranded RNA viruses. The capsid (C), a structural protein of flavivirus, is dimeric and alpha-helical, with several special structural and functional features. The functions of the C protein go far beyond a structural role in virions. It is not only responsible for encapsidation to protect the viral RNA but also able to interact with various host proteins to promote virus proliferation. Therefore, the C protein plays an important role in infected host cells and the viral life cycle. Flaviviruses have been shown to affect the health of humans and animals. Thus, there is an urgent need to effectively control flavivirus infections. The structure of the flavivirus virion has been determined, but there is relatively little information about the function of the C protein. Hence, a greater understanding of the role of the C protein in viral infections will help to discover novel antiviral strategies and provide a promising starting point for the further development of flavivirus vaccines or therapeutics.


Assuntos
Proteínas do Capsídeo/genética , Infecções por Flavivirus/veterinária , Flavivirus/fisiologia , Vacinas Virais/farmacologia , Proteínas do Capsídeo/metabolismo , Infecções por Flavivirus/prevenção & controle , Infecções por Flavivirus/terapia
4.
Cell Rep ; 36(4): 109452, 2021 07 27.
Artigo em Inglês | MEDLINE | ID: mdl-34289385

RESUMO

SARS-CoV-2 variants that attenuate antibody neutralization could jeopardize vaccine efficacy. We recently reported the protective activity of an intranasally administered spike protein-based chimpanzee adenovirus-vectored vaccine (ChAd-SARS-CoV-2-S) in animals, which has advanced to human trials. Here, we assessed its durability, dose response, and cross-protective activity in mice. A single intranasal dose of ChAd-SARS-CoV-2-S induced durably high neutralizing and Fc effector antibody responses in serum and S-specific IgG and IgA secreting long-lived plasma cells in the bone marrow. Protection against a historical SARS-CoV-2 strain was observed across a 100-fold vaccine dose range and over a 200-day period. At 6 weeks or 9 months after vaccination, serum antibodies neutralized SARS-CoV-2 strains with B.1.351, B.1.1.28, and B.1.617.1 spike proteins and conferred almost complete protection in the upper and lower respiratory tracts after challenge with variant viruses. Thus, in mice, intranasal immunization with ChAd-SARS-CoV-2-S provides durable protection against historical and emerging SARS-CoV-2 strains.


Assuntos
Anticorpos Neutralizantes/farmacologia , SARS-CoV-2/patogenicidade , Glicoproteína da Espícula de Coronavírus/imunologia , Vacinas Virais/farmacologia , Administração Intranasal/métodos , Animais , Anticorpos Neutralizantes/imunologia , Anticorpos Antivirais/imunologia , Anticorpos Antivirais/farmacologia , Camundongos , Vacinação/métodos , Vacinas Virais/imunologia
5.
Front Immunol ; 12: 669812, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34220816

RESUMO

Crimean-Congo hemorrhagic fever (CCHF) is a highly severe and virulent viral disease of zoonotic origin, caused by a tick-born CCHF virus (CCHFV). The virus is endemic in many countries and has a mortality rate between 10% and 40%. As there is no licensed vaccine or therapeutic options available to treat CCHF, the present study was designed to focus on application of modern computational approaches to propose a multi-epitope vaccine (MEV) expressing antigenic determinants prioritized from the CCHFV genome. Integrated computational analyses revealed the presence of 9 immunodominant epitopes from Nucleoprotein (N), RNA dependent RNA polymerase (RdRp), Glycoprotein N (Gn/G2), and Glycoprotein C (Gc/G1). Together these epitopes were observed to cover 99.74% of the world populations. The epitopes demonstrated excellent binding affinity for the B- and T-cell reference set of alleles, the high antigenic potential, non-allergenic nature, excellent solubility, zero percent toxicity and interferon-gamma induction potential. The epitopes were engineered into an MEV through suitable linkers and adjuvating with an appropriate adjuvant molecule. The recombinant vaccine sequence revealed all favorable physicochemical properties allowing the ease of experimental analysis in vivo and in vitro. The vaccine 3D structure was established ab initio. Furthermore, the vaccine displayed excellent binding affinity for critical innate immune receptors: TLR2 (-14.33 kcal/mol) and TLR3 (-6.95 kcal/mol). Vaccine binding with these receptors was dynamically analyzed in terms of complex stability and interaction energetics. Finally, we speculate the vaccine sequence reported here has excellent potential to evoke protective and specific immune responses subject to evaluation of downstream experimental analysis.


Assuntos
Antígenos Virais/farmacologia , Biologia Computacional , Desenho Assistido por Computador , Desenvolvimento de Medicamentos , Vírus da Febre Hemorrágica da Crimeia-Congo/imunologia , Febre Hemorrágica da Crimeia/prevenção & controle , Epitopos Imunodominantes , Carrapatos/virologia , Vacinologia , Vacinas Virais/farmacologia , Animais , Antígenos Virais/genética , Antígenos Virais/imunologia , Antígenos Virais/metabolismo , Vírus da Febre Hemorrágica da Crimeia-Congo/genética , Febre Hemorrágica da Crimeia/imunologia , Febre Hemorrágica da Crimeia/virologia , Imunogenicidade da Vacina , Simulação de Acoplamento Molecular , Simulação de Dinâmica Molecular , Receptor 2 Toll-Like/metabolismo , Receptor 3 Toll-Like/metabolismo , Vacinas de DNA/genética , Vacinas de DNA/imunologia , Vacinas de DNA/metabolismo , Vacinas de DNA/farmacologia , Vacinas Virais/genética , Vacinas Virais/imunologia , Vacinas Virais/metabolismo
6.
Nat Commun ; 12(1): 3266, 2021 06 01.
Artigo em Inglês | MEDLINE | ID: mdl-34075032

RESUMO

The epidemic emergence of relatively rare and geographically isolated flaviviruses adds to the ongoing disease burden of viruses such as dengue. Structural analysis is key to understand and combat these pathogens. Here, we present a chimeric platform based on an insect-specific flavivirus for the safe and rapid structural analysis of pathogenic viruses. We use this approach to resolve the architecture of two neurotropic viruses and a structure of dengue virus at 2.5 Å, the highest resolution for an enveloped virion. These reconstructions allow improved modelling of the stem region of the envelope protein, revealing two lipid-like ligands within highly conserved pockets. We show that these sites are essential for viral growth and important for viral maturation. These findings define a hallmark of flavivirus virions and a potential target for broad-spectrum antivirals and vaccine design. We anticipate the chimeric platform to be widely applicable for investigating flavivirus biology.


Assuntos
Infecções por Flavivirus/terapia , Flavivirus/ultraestrutura , Proteínas do Envelope Viral/ultraestrutura , Vírion/ultraestrutura , Aedes/virologia , Animais , Antivirais/farmacologia , Antivirais/uso terapêutico , Linhagem Celular , Chlorocebus aethiops , Microscopia Crioeletrônica , Dengue/terapia , Dengue/virologia , Vacinas contra Dengue/administração & dosagem , Vacinas contra Dengue/farmacologia , Desenho de Fármacos , Flavivirus/efeitos dos fármacos , Flavivirus/imunologia , Flavivirus/patogenicidade , Infecções por Flavivirus/virologia , Humanos , Mesocricetus , Modelos Moleculares , Conformação Molecular , Mutagênese Sítio-Dirigida , Mutação Puntual , Células Vero , Proteínas do Envelope Viral/metabolismo , Vacinas Virais/farmacologia , Vacinas Virais/uso terapêutico , Vírion/efeitos dos fármacos , Vírion/metabolismo
7.
Sci Rep ; 11(1): 12666, 2021 06 16.
Artigo em Inglês | MEDLINE | ID: mdl-34135356

RESUMO

Inactivated poultry vaccines are subject to routine potency testing for batch release, requiring large numbers of animals. The replacement of in vivo tests for cell-based alternatives can be facilitated by the identification of biomarkers for vaccine-induced immune responses. In this study, chicken bone marrow-derived dendritic cells were stimulated with an inactivated vaccine for infectious bronchitis virus and Newcastle disease virus, as well as inactivated infectious bronchitis virus only, and lipopolysaccharides as positive control, or left unstimulated for comparison with the stimulated samples. Next, the cells were lysed and subjected to proteomic analysis. Stimulation with the vaccine resulted in 66 differentially expressed proteins associated with mRNA translation, immune responses, lipid metabolism and the proteasome. For the eight most significantly upregulated proteins, mRNA expression levels were assessed. Markers that showed increased expression at both mRNA and protein levels included PLIN2 and PSMB1. Stimulation with infectious bronchitis virus only resulted in 25 differentially expressed proteins, which were mostly proteins containing Src homology 2 domains. Stimulation with lipopolysaccharides resulted in 118 differentially expressed proteins associated with dendritic cell maturation and antimicrobial activity. This study provides leads to a better understanding of the activation of dendritic cells by an inactivated poultry vaccine, and identified PLIN2 and PSMB1 as potential biomarkers for cell-based potency testing.


Assuntos
Células Dendríticas , Marcadores Genéticos/imunologia , Aves Domésticas/imunologia , Vacinas Virais , Animais , Células da Medula Óssea/efeitos dos fármacos , Células da Medula Óssea/metabolismo , Células Cultivadas/efeitos dos fármacos , Células Cultivadas/metabolismo , Galinhas , Células Dendríticas/efeitos dos fármacos , Células Dendríticas/imunologia , Expressão Gênica/imunologia , Imunidade Inata , Vírus da Bronquite Infecciosa/imunologia , Doença de Newcastle/imunologia , Doença de Newcastle/prevenção & controle , Perilipina-2/imunologia , Perilipina-2/metabolismo , Aves Domésticas/genética , Doenças das Aves Domésticas/imunologia , Doenças das Aves Domésticas/prevenção & controle , Doenças das Aves Domésticas/virologia , Complexo de Endopeptidases do Proteassoma/imunologia , Complexo de Endopeptidases do Proteassoma/metabolismo , Proteômica , Vacinas de Produtos Inativados/imunologia , Vacinas de Produtos Inativados/farmacologia , Vacinas Virais/imunologia , Vacinas Virais/farmacologia
8.
Infect Genet Evol ; 93: 104980, 2021 09.
Artigo em Inglês | MEDLINE | ID: mdl-34182190

RESUMO

This study demonstrates that infectious bronchitis virus (IBV) strain M41, which is pathogenic for chickens, is nonpathogenic for pheasants. However, M41 replicated in the respiratory tracts of most inoculated pheasants and the virus was shed from their respiratory tracts in the early stages of infection (4 and 8 dpc). Similarly, the attenuated IBV H120 vaccine strain also replicated and the virus was shed from their respiratory tracts of most inoculated pheasants, whereas the pheasant coronavirus (PhCoV) I0623/17 replicated in the respiratory tracts of all challenged pheasants, which then shed virus for a long period of time. Strain M41 also replicated in selected tissues of the inoculated pheasants, including the lung, kidney, proventriculus, and cecal tonsil, although the viral titers were very low. Therefore, it was important to establish whether the H120 vaccine, which has a limited replication capacity in pheasants, induces a protective immune response to both "homologous" M41 and "heterologous" I0623/17 challenge. Vaccination with H120 induced humoral responses, and the replication of M41 was reduced or restricted in the tissues of the H120-vaccinated pheasants compared with its replication in unvaccinated birds. This implies that partial protection was conferred on pheasants by vaccination with the H120 vaccine. Prolonged viral replication and a large number of birds shedding virus into the respiratory tract were also observed in the unvaccinated pheasants after inoculation with M41. However, only limited protection against challenge with PhCoV I0623/17 was conferred on pheasants vaccinated with H120, largely because the replication of H120 in pheasants was limited, thus, limiting the immune responses induced by it. The low amino acid identity of the S1 subunit of the S proteins of H120 and I0623/17 might also account, at least in part, for the poor cross-protective immunity induced by H120. These results suggest that further work is required to rationally design vaccines that confer effective protection against PhCoV infection in commercial pheasant stocks.


Assuntos
Infecções por Coronavirus/veterinária , Galliformes , Vírus da Bronquite Infecciosa/fisiologia , Vacinas Virais/farmacologia , Animais , Anticorpos Neutralizantes/imunologia , Infecções por Coronavirus/prevenção & controle , Infecções por Coronavirus/virologia , Vírus da Bronquite Infecciosa/imunologia , Vírus da Bronquite Infecciosa/patogenicidade , Doenças das Aves Domésticas/prevenção & controle , Doenças das Aves Domésticas/virologia , Glicoproteína da Espícula de Coronavírus/química , Glicoproteína da Espícula de Coronavírus/metabolismo , Vacinas Atenuadas/farmacologia
9.
Int J Biol Macromol ; 183: 2162-2173, 2021 Jul 31.
Artigo em Inglês | MEDLINE | ID: mdl-34102236

RESUMO

Effective controls on viral infections rely on the continuous development in vaccine technology. Nanoparticle (NP) antigens are highly immunogenic based on their unique physicochemical properties, making them molecular scaffolds to present soluble vaccine antigens. Here, viral targets (113-354 aas) were genetically fused to N terminal of mi3, a protein that self-assembles into nanoparticles composed of 60 subunits. With transmission electron microscopy, it was confirmed that target-mi3 fusion proteins which have insertions of up to 354 aas in N terminal form intact NPs. Moreover, viral targets are surface-displayed on NPs as indicated in dynamic light scattering. NPs exhibit perfect stability after long-term storage at room temperature. Moreover, SP-E2-mi3 NPs enhance antigen uptake and maturation in dendritic cells (DCs) via up-regulating marker molecules and immunostimulatory cytokines. Importantly, in a mouse model, SP-E2-mi3 nanovaccines against Classical swine fever virus (CSFV) remarkably improved CSFV-specific neutralizing antibodies (NAbs) and cellular immunity related cytokines (IFN-γ and IL-4) as compared to monomeric E2. Specially, improved NAb response with more than tenfold increase in NAb titer against both CSFV Shimen and HZ-08 strains indicated better cross-protection against different genotypes. Collectively, this structure-based, self-assembling NP provides an attractive platform to improve the potency of subunit vaccine for emerging pathogens.


Assuntos
Antígenos Virais/farmacologia , Vírus da Febre Suína Clássica/imunologia , Peste Suína Clássica/prevenção & controle , Imunogenicidade da Vacina , Nanopartículas , Vacinas Virais/farmacologia , Animais , Anticorpos Neutralizantes/sangue , Anticorpos Antivirais/sangue , Antígenos Virais/genética , Antígenos Virais/imunologia , Células Cultivadas , Peste Suína Clássica/sangue , Peste Suína Clássica/imunologia , Peste Suína Clássica/virologia , Citocinas/metabolismo , Células Dendríticas/efeitos dos fármacos , Células Dendríticas/imunologia , Células Dendríticas/metabolismo , Modelos Animais de Doenças , Estabilidade de Medicamentos , Feminino , Camundongos Endogâmicos BALB C , Camundongos Endogâmicos C57BL , Proteínas Recombinantes de Fusão/imunologia , Proteínas Recombinantes de Fusão/farmacologia , Suínos , Temperatura , Vacinas de Subunidades/imunologia , Vacinas de Subunidades/farmacologia , Vacinas Sintéticas/imunologia , Vacinas Sintéticas/farmacologia , Vacinas Virais/imunologia
10.
Front Immunol ; 12: 645210, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33959127

RESUMO

Vaccination is one of the most efficient public healthcare measures to fight infectious diseases. Nevertheless, the immune mechanisms induced in vivo by vaccination are still unclear. The route of administration, an important vaccination parameter, can substantially modify the quality of the response. How the route of administration affects the generation and profile of immune responses is of major interest. Here, we aimed to extensively characterize the profiles of the innate and adaptive response to vaccination induced after intradermal, subcutaneous, or intramuscular administration with a modified vaccinia virus Ankara model vaccine in non-human primates. The adaptive response following subcutaneous immunization was clearly different from that following intradermal or intramuscular immunization. The subcutaneous route induced a higher level of neutralizing antibodies than the intradermal and intramuscular vaccination routes. In contrast, polyfunctional CD8+ T-cell responses were preferentially induced after intradermal or intramuscular injection. We observed the same dichotomy when analyzing the early molecular and cellular immune events, highlighting the recruitment of cell populations, such as CD8+ T lymphocytes and myeloid-derived suppressive cells, and the activation of key immunomodulatory gene pathways. These results demonstrate that the quality of the vaccine response induced by an attenuated vaccine is shaped by early and subtle modifications of the innate immune response. In this immunization context, the route of administration must be tailored to the desired type of protective immune response. This will be achieved through systems vaccinology and mathematical modeling, which will be critical for predicting the efficacy of the vaccination route for personalized medicine.


Assuntos
Anticorpos Neutralizantes/imunologia , Anticorpos Antivirais/imunologia , Linfócitos T CD8-Positivos/imunologia , Células Supressoras Mieloides/imunologia , Vacinação , Vírus Vaccinia/imunologia , Vaccinia/imunologia , Vacinas Virais/farmacologia , Animais , Injeções Intradérmicas , Injeções Intramusculares , Macaca fascicularis , Masculino , Vacinas Atenuadas/farmacologia
11.
PLoS One ; 16(4): e0248001, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33798232

RESUMO

Human T-cell leukemia virus type 1 (HTLV-1) was the first oncogenic human retrovirus identified in humans which infects at least 10-15 million people worldwide. Large HTLV-1 endemic areas exist in Southern Japan, the Caribbean, Central and South America, the Middle East, Melanesia, and equatorial regions of Africa. HTLV-1 TAX viral protein is thought to play a critical role in HTLV-1 associated diseases. We have used numerous bio-informatics and immuno-informatics implements comprising sequence and construction tools for the construction of a 3D model and epitope prediction for HTLV-1 Tax viral protein. The conformational linear B-cell and T-cell epitopes for HTLV-1 TAX viral protein have been predicted for their possible collective use as vaccine candidates. Based on in silico investigation two B cell epitopes, KEADDNDHEPQISPGGLEPPSEKHFR and DGTPMISGPCPKDGQPS spanning from 324-349 and 252-268 respectively; and T cell epitopes, LLFGYPVYV, ITWPLLPHV and GLLPFHSTL ranging from 11-19, 163-171 and 233-241 were found most antigenic and immunogenic epitopes. Among different vaccine constructs generated by different combinations of these epitopes our predicted vaccine construct was found to be most antigenic with a score of 0.57. T cell epitopes interacted strongly with HLA-A*0201 suggesting a significant immune response evoked by these epitopes. Molecular docking study also showed a high binding affinity of the vaccine construct for TLR4. The study was carried out to predict antigenic determinants of the Tax protein along with the 3D protein modeling. The study revealed a potential multi epitope vaccine that can raise the desired immune response against HTLV-1 and be useful in developing effective vaccines against Human T-lymphotropic virus.


Assuntos
Epitopos de Linfócito B/imunologia , Epitopos de Linfócito T/imunologia , Infecções por HTLV-I/prevenção & controle , Vírus Linfotrópico T Tipo 1 Humano/imunologia , Vacinas Virais/imunologia , Produtos do Gene tax/imunologia , Infecções por HTLV-I/imunologia , Humanos , Simulação de Acoplamento Molecular , Receptor 4 Toll-Like/imunologia , Vacinas Virais/farmacologia
12.
J Vet Sci ; 22(3): e30, 2021 May.
Artigo em Inglês | MEDLINE | ID: mdl-33908204

RESUMO

BACKGROUND: New-generation adjuvants for foot-and-mouth disease virus (FMDV) vaccines can improve the efficacy of existing vaccines. Chinese medicinal herb polysaccharide possesses better promoting effects. OBJECTIVES: In this study, the aqueous extract from Artemisia rupestris L. (AEAR), an immunoregulatory crude polysaccharide, was utilized as the adjuvant of inactivated FMDV vaccine to explore their immune regulation roles. METHODS: The mice in each group were subcutaneously injected with different vaccine formulations containing inactivated FMDV antigen adjuvanted with three doses (low, medium, and high) of AEAR or AEAR with ISA-206 adjuvant for 2 times respectively in 1 and 14 days. The variations of antibody level, lymphocyte count, and cytokine secretion in 14 to 42 days after first vaccination were monitored. Then cytotoxic T lymphocyte (CTL) response and antibody duration were measured after the second vaccination. RESULTS: AEAR significantly induced FMDV-specific antibody titers and lymphocyte activation. AEAR at a medium dose stimulated Th1/Th2-type response through interleukin-4 and interferon-γ secreted by CD4⁺ T cells. Effective T lymphocyte counts were significantly elevated by AEAR. Importantly, the efficient CTL response was remarkably provoked by AEAR. Furthermore, AEAR at a low dose and ISA-206 adjuvant also synergistically promoted immune responses more significantly in immunized mice than those injected with only ISA-206 adjuvant and the stable antibody duration without body weight loss was 6 months. CONCLUSIONS: These findings suggested that AEAR had potential utility as a polysaccharide adjuvant for FMDV vaccines.


Assuntos
Artemisia/química , Vírus da Febre Aftosa/imunologia , Febre Aftosa/prevenção & controle , Extratos Vegetais/farmacologia , Polissacarídeos/farmacologia , Vacinas Virais/farmacologia , Adjuvantes Imunológicos/farmacologia , Animais , Relação Dose-Resposta a Droga , Feminino , Camundongos , Camundongos Endogâmicos ICR , Extratos Vegetais/química , Distribuição Aleatória , Vacinas de Produtos Inativados/farmacologia
13.
Front Immunol ; 12: 645426, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33659011

RESUMO

Marek's disease virus (MDV) is a highly oncogenic alphaherpesvirus that causes deadly T-cell lymphomas and serves as a natural virus-induced tumor model in chickens. The most efficacious vaccine, CVI988/Rispens (CVI988), against MD has been used for several decades. However, the mechanisms leading to protective immunity following vaccination are not fully understood. In this study, employing multi-parameter flow cytometry, we performed a comprehensive analysis of T cell responses in CVI988-vaccinated chickens. CVI988 vaccination induced significant expansion of γδ T cells and CD8α+ T cells but not CD4+ T cells in spleen, lung and blood at early time-points. The expansion of these cells was CVI988-specific as infection with very virulent MDV RB1B did not elicit expansion of either γδ or CD8α+ T cells. Phenotypic analysis showed that CVI988 vaccination elicited preferential proliferation of CD8α+ γδ T cells and CD8αα co-receptor expression was upregulated on γδ T cells and CD8α+ T cells after immunization. Additionally, cell sorting and quantitative RT-PCR showed that CVI988 vaccination activated γδ T cells and CD8α+ T cells which exhibited differential expression of cytotoxic and T cell-related cytokines. Lastly, secondary immunization with CVI988 induced the expansion of CD8+ T cells but not γδ T cells at higher magnitude, compared to primary immunization, suggesting CVI988 did induce memory CD8+ T cells but not γδ T cells in chickens. Our results, for the first time, reveal a potential role of γδ T cells in CVI988-induced immune protection and provide new insights into the mechanism of immune protection against oncogenic MDV.


Assuntos
Linfócitos T CD8-Positivos/imunologia , Vacinas Anticâncer/farmacologia , Galinhas , Herpesvirus Galináceo 2/imunologia , Doenças das Aves Domésticas , Receptores de Antígenos de Linfócitos T gama-delta/imunologia , Vacinas Virais/farmacologia , Animais , Galinhas/imunologia , Galinhas/virologia , Doença de Marek/imunologia , Doença de Marek/prevenção & controle , Doenças das Aves Domésticas/imunologia , Doenças das Aves Domésticas/prevenção & controle , Doenças das Aves Domésticas/virologia , Vacinação
14.
Eur J Pharmacol ; 896: 173930, 2021 Apr 05.
Artigo em Inglês | MEDLINE | ID: mdl-33545157

RESUMO

The severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), which emerged in December 2019 and caused the coronavirus disease 2019 (COVID-19) pandemic, took the world by surprise with an unprecedented public health emergency. Since this pandemic began, extraordinary efforts have been made by scientists to understand the pathogenesis of COVID-19, and to fight the infection by providing various preventive, diagnostic and treatment opportunities based on either novel hypotheses or past experiences. Despite all the achievements, COVID-19 continues to be an accelerating health threat with no specifically approved vaccine or therapy. This review highlights the recent advances in COVID-19 infection, with a particular emphasis on nanomedicine applications that can help in the development of effective vaccines or therapeutics against COVID-19. A novel future perspective has been proposed in this review based on utilizing polymersome nano-objects for effectively suppressing the cytokine storm, which may reduce the severity of COVID-19 infection.


Assuntos
Antivirais/farmacologia , COVID-19 , Nanomedicina/métodos , SARS-CoV-2/efeitos dos fármacos , Vacinas Virais/farmacologia , COVID-19/tratamento farmacológico , COVID-19/epidemiologia , COVID-19/prevenção & controle , Desenvolvimento de Medicamentos , Humanos
16.
Expert Opin Drug Discov ; 16(2): 115-117, 2021 02.
Artigo em Inglês | MEDLINE | ID: mdl-32915657

RESUMO

Introduction: The COVID-19 pandemic has catalyzed the production of potential antivirals and vaccines from research organizations across the globe. The initial step for all drug discovery models is the identification of suitable targets. One approach organizations may take to tackle this involves issuing raw data publicly for collaboration with other organizations in order to spark discussion, collectively experiment and stay up to date with advances in scientific knowledge. Areas covered: Numerous organizations have released genomic data, amongst other tools, for the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) and this has led to the development of growing datasets of knowledge for continued collaboration amongst different scientific communities. A different technique employs a more closed, market-driven method in order to stay ahead financially in the race for developing a suitable antiviral or vaccine. The latter allows sustained motivation for company ambitions and progress has been made toward clinical trials for potential drugs. Expert opinion: A case can be made for both open and closed drug discovery models; however, due to the rapidly evolving nature of this deadly virus, organizations should collate their research and support one another to ensure satisfactory treatment can be approved in a timely manner.


Assuntos
Antivirais/farmacologia , COVID-19/tratamento farmacológico , Descoberta de Drogas/organização & administração , SARS-CoV-2 , Vacinas Virais/farmacologia , COVID-19/epidemiologia , COVID-19/prevenção & controle , Ensaios Clínicos como Assunto , Descoberta de Drogas/economia , Descoberta de Drogas/métodos , Humanos , Cooperação Internacional , SARS-CoV-2/efeitos dos fármacos , SARS-CoV-2/genética
17.
Front Immunol ; 11: 576012, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33343565

RESUMO

Therapeutics based on fusing a protein of interest to the IgG Fc domain have been enormously successful, though fewer studies have investigated the vaccine potential of IgG fusions. In this study, we systematically compared the key properties of seven different plant-made human IgG1 fusion vaccine candidates using Zika virus (ZIKV) envelope domain III (ZE3) as a model antigen. Complement protein C1q binding of the IgG fusions was enhanced by: 1) antigen fusion to the IgG N-terminus; 2) removal of the IgG light chain or Fab regions; 3) addition of hexamer-inducing mutations in the IgG Fc; 4) adding a self-binding epitope tag to create recombinant immune complexes (RIC); or 5) producing IgG fusions in plants that lack plant-specific ß1,2-linked xylose and α1,3-linked fucose N-linked glycans. We also characterized the expression, solubility, and stability of the IgG fusions. By optimizing immune complex formation, a potently immunogenic vaccine candidate with improved solubility and high stability was produced at 1.5 mg IgG fusion per g leaf fresh weight. In mice, the IgG fusions elicited high titers of Zika-specific antibodies which neutralized ZIKV using only two doses without adjuvant, reaching up to 150-fold higher antibody titers than ZE3 antigen alone. We anticipate these findings will be broadly applicable to the creation of other vaccines and antibody-based therapeutics.


Assuntos
Antígenos Virais/farmacologia , Imunogenicidade da Vacina , Imunoglobulina G/farmacologia , Proteínas do Envelope Viral/farmacologia , Vacinas Virais/farmacologia , Infecção por Zika virus/prevenção & controle , Zika virus/imunologia , Animais , Anticorpos Neutralizantes/sangue , Anticorpos Antivirais/sangue , Antígenos Virais/genética , Antígenos Virais/imunologia , Complemento C1q/metabolismo , Estabilidade de Medicamentos , Epitopos , Feminino , Imunização , Imunoglobulina G/genética , Imunoglobulina G/imunologia , Camundongos Endogâmicos BALB C , Folhas de Planta/genética , Folhas de Planta/metabolismo , Plantas Geneticamente Modificadas/genética , Plantas Geneticamente Modificadas/metabolismo , Ligação Proteica , Proteínas Recombinantes de Fusão/farmacologia , Solubilidade , Tabaco/genética , Tabaco/metabolismo , Vacinas de Subunidades/farmacologia , Proteínas do Envelope Viral/genética , Proteínas do Envelope Viral/imunologia , Vacinas Virais/genética , Vacinas Virais/imunologia , Zika virus/patogenicidade , Infecção por Zika virus/imunologia , Infecção por Zika virus/virologia
18.
Biomed Pharmacother ; 132: 110914, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-33254432

RESUMO

The occurrence of the SARS-CoV2 infection has become a worldwide threat and the urgent need to discover therapeutic interventions remains paramount. The primary roles of the coronavirus nucleocapsid (N) protein are to interact with the viral genome and pack them into ribonucleoprotein complex. It also plays critical roles at many stages of the viral life cycle. Herein, we explore the N protein of SARS-CoV2 to identify promising epitope-based vaccine candidates and target the N-terminal domain of SARS-CoV2 N-protein for potential inhibitors using an integrative bioinformatics approach. We identified B-cell epitopes and T-cell epitopes that are non-toxic, non-allergenic, capable of inducing IFN-γ and structurally stable with high global population coverage of response. The 404SKQLQQSMSSADS416 and 92RRIRGGDGKMKDL104 sequences of N-protein were identified to induce B-cell immunity. We also identified 79SSPDDQIGY87 and 305AQFAPSASAFFGMSR319 as potential T-cell epitopes that form stable structures with human leucocyte antigens. We have also identified zidovudine triphosphate, an anti-HIV agent, as a potential inhibitor of the N-terminal domain of SARS-CoV2 N-protein based on docking and simulation analysis and should be considered for experimental validations. The findings of this study can help fast-track the discovery of therapeutic options to combat COVID-19.


Assuntos
COVID-19 , Proteínas do Nucleocapsídeo de Coronavírus/fisiologia , Descoberta de Drogas/métodos , SARS-CoV-2 , Vacinas Virais/farmacologia , Antivirais/farmacologia , COVID-19/tratamento farmacológico , COVID-19/virologia , Biologia Computacional/métodos , Epitopos/imunologia , Humanos , Simulação de Acoplamento Molecular/métodos , Fosfoproteínas/fisiologia , SARS-CoV-2/efeitos dos fármacos , SARS-CoV-2/fisiologia , Zidovudina/farmacologia
20.
Aust J Gen Pract ; 49(10): 625-629, 2020 10.
Artigo em Inglês | MEDLINE | ID: mdl-33015676

RESUMO

BACKGROUND: The availability of a COVID-19 vaccine is being heralded as the solution to control the current COVID-19 pandemic, reduce the number of infections and deaths and facilitate resumption of our previous way of life. OBJECTIVE: The aim of this article is to provide a framework for primary care of what will be needed to optimise COVID-19 vaccine confidence and uptake in Australia once the vaccine prioritisation schedule and key target groups are known. DISCUSSION: While a number of vaccines are currently under development, with at least seven undergoing phase III trials (28 August 2020), it is hoped that an effective COVID-19 vaccine will become available to the public in 2021. Ensuring public confidence in vaccine safety and effectiveness will be crucial to facilitate uptake. General practitioners are at the forefront of public health, and one of the most trusted sources for patients. In this article, the authors discuss the expedited vaccine development process for COVID-19 vaccines; the likely vaccine prioritisation schedule and anticipated key target groups; the behavioural and social drivers of vaccination acceptance, including the work required to facilitate this; and the implications for general practice.


Assuntos
Infecções por Coronavirus , Clínicos Gerais/psicologia , Programas de Imunização/organização & administração , Pandemias , Pneumonia Viral , Saúde Pública/métodos , Vacinação , Vacinas Virais/farmacologia , Austrália , Betacoronavirus , COVID-19 , Vacinas contra COVID-19 , Infecções por Coronavirus/epidemiologia , Infecções por Coronavirus/prevenção & controle , Grupos Focais , Acesso aos Serviços de Saúde/organização & administração , Humanos , Pandemias/prevenção & controle , Aceitação pelo Paciente de Cuidados de Saúde , Pneumonia Viral/epidemiologia , Pneumonia Viral/prevenção & controle , Atenção Primária à Saúde/métodos , SARS-CoV-2 , Autoimagem , Vacinação/métodos , Vacinação/psicologia
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