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1.
Front Immunol ; 12: 728513, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34484238

RESUMO

VITT is a rare, life-threatening syndrome characterized by thrombotic symptoms in combination with thrombocytopenia, which may occur in individuals receiving the first administration of adenoviral non replicating vectors (AVV) anti Covid19 vaccines. Vaccine-induced immune thrombotic thrombocytopenia (VITT) is characterized by high levels of serum IgG that bind PF4/polyanion complexes, thus triggering platelet activation. Therefore, identification of the fine pathophysiological mechanism by which vaccine components trigger platelet activation is mandatory. Herein, we propose a multistep mechanism involving both the AVV and the neo-synthetized Spike protein. The former can: i) spread rapidly into blood stream, ii), promote the early production of high levels of IL-6, iii) interact with erythrocytes, platelets, mast cells and endothelia, iv) favor the presence of extracellular DNA at the site of injection, v) activate platelets and mast cells to release PF4 and heparin. Moreover, AVV infection of mast cells may trigger aberrant inflammatory and immune responses in people affected by the mast cell activation syndrome (MCAS). The pre-existence of natural antibodies binding PF4/heparin complexes may amplify platelet activation and thrombotic events. Finally, neosynthesized Covid 19 Spike protein interacting with its ACE2 receptor on endothelia, platelets and leucocyte may trigger further thrombotic events unleashing the WITT syndrome.


Assuntos
Anticorpos/efeitos adversos , Vacinas contra COVID-19/efeitos adversos , COVID-19/prevenção & controle , Púrpura Trombocitopênica Idiopática/induzido quimicamente , Púrpura Trombocitopênica Idiopática/fisiopatologia , Adenoviridae/genética , Animais , Plaquetas/imunologia , Plaquetas/patologia , Vacinas contra COVID-19/imunologia , Modelos Animais de Doenças , Vetores Genéticos , Humanos , Camundongos , Ativação Plaquetária/imunologia , Fator Plaquetário 4 , Coelhos
2.
Biomaterials ; 276: 121062, 2021 09.
Artigo em Inglês | MEDLINE | ID: mdl-34418816

RESUMO

Adenovirus (Ad) has been extensively developed as a gene delivery vector, but the potential side effect caused by systematic immunization remains one major obstacle for its clinical application. Needle-free mucosal immunization with Ad-based vaccine shows advantages but still faces poor mucosal responses. We herein report that the chemical engineering of single live viral-based vaccine effectively modulated the location and pattern of the subsequently elicited immunity. Through precisely assembly of functional materials onto single live Ad particle, the modified virus entered host cell in a phagocytosis-dependent manner, which is completely distinct from the receptor-mediated entry of native Ad. RNA-Seq data further demonstrated that the modified Ad-induced innate immunity was sharply reshaped via phagocytosis-related pathway, therefore promoting the activation and mature of antigen presentation cells (APC). Moreover, the functional shell enabled the modified Ad-based vector with enhanced muco-adhesion to nasal tissues in mice, and then prolonged resident time onto mucosal surface, leading to the robust mucosal IgA production and T cell immunity at local and even remote mucosal-associated lymphoid tissues. This study demonstrated that vaccine-induced immunity can be well modulated by chemistry engineering, and this method provides the rational design for needle-free mucosa-targeting vaccine against a variety of emerging infectious diseases.


Assuntos
Vacinas Virais , Adenoviridae/genética , Animais , Vetores Genéticos , Imunidade nas Mucosas , Camundongos , Fagocitose
4.
Viruses ; 13(7)2021 07 02.
Artigo em Inglês | MEDLINE | ID: mdl-34372506

RESUMO

Adenovirus-based vectors are playing an important role as efficacious genetic vaccines to fight the current COVID-19 pandemic. Furthermore, they have an enormous potential as oncolytic vectors for virotherapy and as vectors for classic gene therapy. However, numerous vector-host interactions on a cellular and noncellular level, including specific components of the immune system, must be modulated in order to generate safe and efficacious vectors for virotherapy or classic gene therapy. Importantly, the current widespread use of Ad vectors as vaccines against COVID-19 will induce antivector immunity in many humans. This requires the development of strategies and techniques to enable Ad-based vectors to evade pre-existing immunity. In this review article, we discuss the current status of genetic and chemical capsid modifications as means to modulate the vector-host interactions of Ad-based vectors.


Assuntos
Adenoviridae/genética , COVID-19/prevenção & controle , Capsídeo/química , Adenoviridae/imunologia , COVID-19/imunologia , COVID-19/terapia , Vacinas contra COVID-19/administração & dosagem , Vacinas contra COVID-19/imunologia , Genes Virais , Vetores Genéticos , Humanos , Imunidade , Terapia Viral Oncolítica/métodos , Pandemias , SARS-CoV-2/imunologia , SARS-CoV-2/isolamento & purificação
6.
Sci Rep ; 11(1): 14917, 2021 07 21.
Artigo em Inglês | MEDLINE | ID: mdl-34290317

RESUMO

We have developed a COVID-19 vaccine, hAd5 S-Fusion + N-ETSD, that expresses SARS-CoV-2 spike (S) and nucleocapsid (N) proteins with modifications to increase immune responses delivered using a human adenovirus serotype 5 (hAd5) platform. Here, we demonstrate subcutaneous (SC) prime and SC boost vaccination of CD-1 mice with this dual-antigen vaccine elicits T-helper cell 1 (Th1) biased T-cell and humoral responses to both S and N that are greater than those seen with hAd5 S wild type delivering only unmodified S. We then compared SC to intranasal (IN) prime vaccination with SC or IN boosts and show that an IN prime with an IN boost is as effective at generating Th1 biased humoral responses as the other combinations tested, but an SC prime with an IN or SC boost elicits greater T cell responses. Finally, we used a combined SC plus IN (SC + IN) prime with or without a boost and found the SC + IN prime alone to be as effective in generating humoral and T-cell responses as the SC + IN prime with a boost. The finding that SC + IN prime-only delivery has the potential to provide broad immunity-including mucosal immunity-against SARS-CoV-2 supports further testing of this vaccine and delivery approach in animal models of viral challenge.


Assuntos
Vacinas contra COVID-19/administração & dosagem , COVID-19/imunologia , COVID-19/prevenção & controle , SARS-CoV-2/imunologia , Adenoviridae/genética , Administração Intranasal , Animais , Anticorpos Neutralizantes , Anticorpos Antivirais/biossíntese , Anticorpos Antivirais/imunologia , Vacinas contra COVID-19/imunologia , Feminino , Vetores Genéticos , Hipodermóclise , Imunidade Celular/imunologia , Imunidade nas Mucosas/imunologia , Imunização Secundária , Camundongos , Camundongos Endogâmicos , Vacinação/métodos
8.
Cell Death Dis ; 12(7): 663, 2021 07 02.
Artigo em Inglês | MEDLINE | ID: mdl-34230456

RESUMO

A majority of mesothelioma specimens were defective of p14 and p16 expression due to deletion of the INK4A/ARF region, and the p53 pathway was consequently inactivated by elevated MDM2 functions which facilitated p53 degradaton. We investigated a role of p53 elevation by MDM2 inhibitors, nutlin-3a and RG7112, in cytotoxicity of replication-competent adenoviruses (Ad) lacking the p53-binding E1B55kDa gene (Ad-delE1B). We found that a growth inhibition by p53-activating Ad-delE1B was irrelevant to p53 expression in the infected cells, but combination of Ad-delE1B and the MDM2 inhibitor produced synergistic inhibitory effects on mesothelioma with the wild-type but not mutated p53 genotype. The combination augmented p53 phosphorylation, activated apoptotic but not autophagic pathway, and enhanced DNA damage signals through ATM-Chk2 phosphorylation. The MDM2 inhibitors facilitated production of the Ad progenies through augmented expression of nuclear factor I (NFI), one of the transcriptional factors involved in Ad replications. Knocking down of p53 with siRNA did not increase the progeny production or the NFI expression. We also demonstrated anti-tumor effects by the combination of Ad-delE1B and the MDM2 inhibitors in an orthotopic animal model. These data collectively indicated that upregulation of wild-type p53 expression contributed to cytotoxicity by E1B55kDa-defective replicative Ad through NFI induction and suggested that replication-competent Ad together with augmented p53 levels was a therapeutic strategy for p53 wild-type mesothelioma.


Assuntos
Adenoviridae/genética , Proteínas E1 de Adenovirus/genética , Antineoplásicos/farmacologia , Imidazóis/farmacologia , Imidazolinas/farmacologia , Mesotelioma/terapia , Neurofibromina 1/metabolismo , Terapia Viral Oncolítica , Vírus Oncolíticos/genética , Piperazinas/farmacologia , Proteínas Proto-Oncogênicas c-mdm2/antagonistas & inibidores , Proteína Supressora de Tumor p53/metabolismo , Adenoviridae/crescimento & desenvolvimento , Animais , Apoptose/efeitos dos fármacos , Proteínas Reguladoras de Apoptose/genética , Proteínas Reguladoras de Apoptose/metabolismo , Linhagem Celular Tumoral , Quimioterapia Adjuvante , Regulação Neoplásica da Expressão Gênica , Mesotelioma/genética , Mesotelioma/metabolismo , Mesotelioma/virologia , Camundongos Endogâmicos BALB C , Camundongos Nus , Neurofibromina 1/genética , Vírus Oncolíticos/crescimento & desenvolvimento , Proteínas Proto-Oncogênicas c-mdm2/genética , Proteínas Proto-Oncogênicas c-mdm2/metabolismo , Carga Tumoral/efeitos dos fármacos , Proteína Supressora de Tumor p53/genética , Replicação Viral , Ensaios Antitumorais Modelo de Xenoenxerto
9.
Nat Immunol ; 22(8): 1042-1051, 2021 08.
Artigo em Inglês | MEDLINE | ID: mdl-34267375

RESUMO

Pathogens and vaccines that produce persisting antigens can generate expanded pools of effector memory CD8+ T cells, described as memory inflation. While properties of inflating memory CD8+ T cells have been characterized, the specific cell types and tissue factors responsible for their maintenance remain elusive. Here, we show that clinically applied adenovirus vectors preferentially target fibroblastic stromal cells in cultured human tissues. Moreover, we used cell-type-specific antigen targeting to define critical cells and molecules that sustain long-term antigen presentation and T cell activity after adenovirus vector immunization in mice. While antigen targeting to myeloid cells was insufficient to activate antigen-specific CD8+ T cells, genetic activation of antigen expression in Ccl19-cre-expressing fibroblastic stromal cells induced inflating CD8+ T cells. Local ablation of vector-targeted cells revealed that lung fibroblasts support the protective function and metabolic fitness of inflating memory CD8+ T cells in an interleukin (IL)-33-dependent manner. Collectively, these data define a critical fibroblastic niche that underpins robust protective immunity operating in a clinically important vaccine platform.


Assuntos
Adenoviridae/imunologia , Linfócitos T CD8-Positivos/imunologia , Memória Imunológica/imunologia , Interleucina-33/imunologia , Ativação Linfocitária/imunologia , Células Estromais/imunologia , Adenoviridae/genética , Animais , Linhagem Celular Tumoral , Quimiocina CCL19/metabolismo , Quimera/genética , Epitopos de Linfócito T/imunologia , Fibroblastos/citologia , Fibroblastos/metabolismo , Vetores Genéticos/imunologia , Humanos , Pulmão/citologia , Melanoma Experimental/imunologia , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Vacinação
10.
Emerg Microbes Infect ; 10(1): 1574-1588, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34289779

RESUMO

A safe and effective vaccine is urgently needed to control the unprecedented COVID-19 pandemic. Four adenovirus-vectored vaccines expressing spike (S) protein have been approved for use. Here, we generated several recombinant chimpanzee adenovirus (AdC7) vaccines expressing S, receptor-binding domain (RBD), or tandem-repeat dimeric RBD (RBD-tr2). We found vaccination via either intramuscular or intranasal route was highly immunogenic in mice to elicit both humoral and cellular immune responses. AdC7-RBD-tr2 showed higher antibody responses compared to either AdC7-S or AdC7-RBD. Intranasal administration of AdC7-RBD-tr2 additionally induced mucosal immunity with neutralizing activity in bronchoalveolar lavage fluid. Either single-dose or two-dose mucosal administration of AdC7-RBD-tr2 protected mice against SARS-CoV-2 challenge, with undetectable subgenomic RNA in lung and relieved lung injury. AdC7-RBD-tr2-elicted sera preserved the neutralizing activity against the circulating variants, especially the Delta variant. These results support AdC7-RBD-tr2 as a promising COVID-19 vaccine candidate.


Assuntos
Adenoviridae/genética , Anticorpos Antivirais/sangue , Vacinas contra COVID-19/imunologia , Glicoproteína da Espícula de Coronavírus/imunologia , Administração Intranasal , Animais , Anticorpos Neutralizantes/sangue , COVID-19 , Vacinas contra COVID-19/administração & dosagem , Vacinas contra COVID-19/genética , Chlorocebus aethiops , Feminino , Vetores Genéticos/genética , Células HEK293 , Humanos , Imunogenicidade da Vacina , Injeções Intramusculares , Camundongos , Camundongos Endogâmicos BALB C , Pan troglodytes/virologia , Ligação Proteica , SARS-CoV-2/genética , SARS-CoV-2/imunologia , Glicoproteína da Espícula de Coronavírus/administração & dosagem , Glicoproteína da Espícula de Coronavírus/genética , Vacinação , Células Vero
11.
Zhongguo Gu Shang ; 34(7): 674-9, 2021 Jul 25.
Artigo em Chinês | MEDLINE | ID: mdl-34318647

RESUMO

OBJECTIVE: To construct and identify adenovirus vector co-expressing hBMP2 and hVEGF165 fusion protein which labeled with green fluorescence protein, and laying the foundtion of the effect of hBMP2 and hVEGF165 gene inducing BMMSCs differentiation to osteoblast and bone defect repaired in the body. METHODS: BMP2 and VEGF165 gene was amplified from cDNA library by PCR and inserted to the polyclonal site of adenovirus shuttle plasmid pAd-MCMV-GFP. Ad-BMP2- VEGF165 was recombinated and propagated in HEK293 cells by co-transfecting with the constructed recombinant shuttle plasmid pAd-MCMV-BMP2-VEGF165 and adenovirus helper plasmid pBHGloxΔ E1, 3Cre. The recombinant adenovirus was purified and virustiter was determined, and then to research GFP expression and to calculate the adenovirus transfection rate in rabbit BMMSCs. RESULTS: The recombinant adenovirus vector Ad-BMP2-VEGF165 was successfully constructed by the methods of gene analyzing, colony PCR, Western blotting and observing GFP expression, and the titer of the adenovirus was 1×1010 PFU /ml. CONCLUSION: Recombinant adenovirus vector containing hBMP2 and hVEGF165 gene was successfully constructed and its high titer was obtained.


Assuntos
Células-Tronco Mesenquimais , Adenoviridae/genética , Animais , Células da Medula Óssea , Vetores Genéticos/genética , Células HEK293 , Humanos , Coelhos , Transfecção
12.
Anticancer Res ; 41(8): 3731-3740, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-34281831

RESUMO

BACKGROUND: The clustered regularly interspaced short palindromic repeats-associated protein 9 (CRISPR-Cas9) is thought to have promising clinical potential. However, the off-target effects of Cas9 are a major concern for its application. Therefore, we hypothesized that the adverse effects of off-target gene editing might be minimized if the human codon-optimized Streptococcus pyogenes Cas9 (hCas9) could be specifically expressed in cancer cells. MATERIALS AND METHODS: We constructed a chimeric adenoviral vector, Ad5F35-MKp-hCas9, and infected human bladder cancer cell lines with this vector. The confirmation of hCas9 gene expression was performed in 3-4 days after from infection. RESULTS: hCas9 gene expression was observed in Ad5F35-MKp-hCas9 infected bladder cancer cells but not in non-malignant cells. CONCLUSION: Our study showed that the Ad5F35-MKp-hCas9 vector is capable of expressing the hCas9 gene with high specificity in bladder cancer cells. These findings may help in minimizing the risk of off-target effects of gene editing.


Assuntos
Adenoviridae/genética , Proteína 9 Associada à CRISPR/genética , Vetores Genéticos/genética , Transfecção/métodos , Neoplasias da Bexiga Urinária/genética , Proteína 9 Associada à CRISPR/metabolismo , Linhagem Celular Tumoral , Sobrevivência Celular/genética , Edição de Genes/métodos , Regulação Neoplásica da Expressão Gênica , Células HEK293 , Humanos , Regiões Promotoras Genéticas , Neoplasias da Bexiga Urinária/patologia
13.
J Infect Dev Ctries ; 15(6): 761-765, 2021 06 30.
Artigo em Inglês | MEDLINE | ID: mdl-34242183

RESUMO

INTRODUCTION: The aim of this study is to determine the coinfections with other respiratory pathogens in SARS-CoV-2 infected children patients in a pediatric unit in Istanbul. METHODOLOGY: This retrospective descriptive study was conducted in a 1000-bedded tertiary education and research hospital in Istanbul. All children hospitalized with the diagnosis of SARS-CoV-2 infection had been investigated for respiratory agents in nasopharyngeal secretions. Laboratory confirmation of SARS-CoV-2 and the other respiratory pathogens were performed using reverse transcriptase-polymerase chain reaction (RT-PCR). RESULTS: A total of 209 hospitalized children with suspected SARS-CoV-2 infection between March 2020-May 2020 were enrolled in this study. Among 209 children, 93 (44.5%) were RT-PCR positive for SARS-CoV-2 infection, and 116 (55.5%) were RT-PCR negative. The most common clinical symptoms in all children with SARS-CoV-2 infection were fever (68.8%) and cough (57.0%). The other clinical symptoms in decreasing rates were headache (10.8%), myalgia (5.4%), sore throat (3.2%), shortness of breath (3.2%), diarrhea (2.2%) and abdominal pain in one child. In 7 (7.5%) patients with SARS-CoV-2 infection, coinfection was detected. Two were with rhinovirus/enterovirus, two were with Coronavirus NL63, one was with adenovirus, and one was with Mycoplasma pneumoniae. In one patient, two additional respiratory agents (rhinovirus/enterovirus and adenovirus) were detected. There was a significantly longer hospital stay in patients with coinfection (p = 0.028). CONCLUSIONS: Although the coinfection rate was low in SARS-CoV-2 infected patients in our study, we found coinfection as a risk factor for length of hospital stay in the coinfected patient group.


Assuntos
COVID-19/microbiologia , COVID-19/virologia , Coinfecção/microbiologia , Coinfecção/virologia , Vírus/genética , Adenoviridae/genética , Adolescente , COVID-19/diagnóstico , Criança , Pré-Escolar , Coinfecção/diagnóstico , Coinfecção/epidemiologia , Hospitalização/estatística & dados numéricos , Humanos , Tempo de Internação/estatística & dados numéricos , Mycoplasma pneumoniae/genética , Mycoplasma pneumoniae/isolamento & purificação , Nasofaringe/microbiologia , Nasofaringe/virologia , Pesquisa Qualitativa , Sistema Respiratório/microbiologia , Sistema Respiratório/virologia , Estudos Retrospectivos , SARS-CoV-2/genética , Centros de Atenção Terciária/estatística & dados numéricos , Turquia/epidemiologia , Vírus/classificação , Vírus/isolamento & purificação
14.
Virus Res ; 302: 198466, 2021 09.
Artigo em Inglês | MEDLINE | ID: mdl-34087261

RESUMO

Vigorous vaccination programs against SARS-CoV-2-causing Covid-19 are the major chance to fight this dreadful pandemic. The currently administered vaccines depend on adenovirus DNA vectors or on SARS-CoV-2 mRNA that might become reverse transcribed into DNA, however infrequently. In some societies, people have become sensitized against the potential short- or long-term side effects of foreign DNA being injected into humans. In my laboratory, the fate of foreign DNA in mammalian (human) cells and organisms has been investigated for many years. In this review, a summary of the results obtained will be presented. This synopsis has been put in the evolutionary context of retrotransposon insertions into pre-human genomes millions of years ago. In addition, studies on adenovirus vector-based DNA, on the fate of food-ingested DNA as well as the long-term persistence of SARS-CoV-2 RNA/DNA will be described. Actual integration of viral DNA molecules and of adenovirus vector DNA will likely be chance events whose frequency and epigenetic consequences cannot with certainty be assessed. The review also addresses problems of remaining adenoviral gene expression in adenoviral-based vectors and their role in side effects of vaccines. Eventually, it will come down to weighing the possible risks of genomic insertions of vaccine-associated foreign DNA and unknown levels of vector-carried adenoviral gene expression versus protection against the dangers of Covid-19. A decision in favor of vaccination against life-threatening disease appears prudent. Informing the public about the complexities of biology will be a reliable guide when having to reach personal decisions about vaccinations.


Assuntos
Adenoviridae/genética , Vacinas contra COVID-19/genética , COVID-19/prevenção & controle , Genoma Humano/genética , Pandemias , SARS-CoV-2/imunologia , Vacinação , COVID-19/epidemiologia , COVID-19/virologia , DNA Viral/genética , Expressão Gênica , Vetores Genéticos/genética , Humanos , RNA Mensageiro/genética , RNA Viral/genética , SARS-CoV-2/genética
15.
Viruses ; 13(5)2021 05 08.
Artigo em Inglês | MEDLINE | ID: mdl-34066836

RESUMO

We previously developed a refined, tumor-selective adenovirus, Ad5NULL-A20, harboring tropism ablating mutations in each major capsid protein, to ablate all native means of infection. We incorporated a 20-mer peptide (A20) in the fiber knob for selective infection via αvß6 integrin, a marker of aggressive epithelial cancers. Methods: To ascertain the selectivity of Ad5NULL-A20 for αvß6-positive tumor cell lines of pancreatic and breast cancer origin, we performed reporter gene and cell viability assays. Biodistribution of viral vectors in mice harboring xenografts with low, medium, and high αvß6 levels was quantified by qPCR for viral genomes 48 h post intravenous administration. Results: Ad5NULL-A20 vector transduced cells in an αvß6-selective manner, whilst cell killing mediated by oncolytic Ad5NULL-A20 was αvß6-selective. Biodistribution analysis following intravenous administration into mice bearing breast cancer xenografts demonstrated that Ad5NULL-A20 resulted in significantly reduced liver accumulation coupled with increased tumor accumulation compared to Ad5 in all three models, with tumor-to-liver ratios improved as a function of αvß6 expression. Conclusions: Ad5NULL-A20-based virotherapies efficiently target αvß6-integrin-positive tumors following intravenous administration, validating the potential of Ad5NULL-A20 for systemic applications, enabling tumor-selective overexpression of virally encoded therapeutic transgenes.


Assuntos
Adenoviridae/genética , Antígenos de Neoplasias/genética , Terapia Genética , Vetores Genéticos/genética , Integrinas/genética , Neoplasias/terapia , Terapia Viral Oncolítica , Vírus Oncolíticos/genética , Administração Intravenosa , Animais , Linhagem Celular Tumoral , Sobrevivência Celular , Modelos Animais de Doenças , Terapia Genética/métodos , Vetores Genéticos/administração & dosagem , Humanos , Camundongos , Neoplasias/etiologia , Terapia Viral Oncolítica/métodos , Transdução Genética , Resultado do Tratamento , Ensaios Antitumorais Modelo de Xenoenxerto
16.
PLoS One ; 16(6): e0252534, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34133435

RESUMO

Many recent disease outbreaks in humans had a zoonotic virus etiology. Bats in particular have been recognized as reservoirs to a large variety of viruses with the potential to cross-species transmission. In order to assess the risk of bats in Switzerland for such transmissions, we determined the virome of tissue and fecal samples of 14 native and 4 migrating bat species. In total, sequences belonging to 39 different virus families, 16 of which are known to infect vertebrates, were detected. Contigs of coronaviruses, adenoviruses, hepeviruses, rotaviruses A and H, and parvoviruses with potential zoonotic risk were characterized in more detail. Most interestingly, in a ground stool sample of a Vespertilio murinus colony an almost complete genome of a Middle East respiratory syndrome-related coronavirus (MERS-CoV) was detected by Next generation sequencing and confirmed by PCR. In conclusion, bats in Switzerland naturally harbour many different viruses. Metagenomic analyses of non-invasive samples like ground stool may support effective surveillance and early detection of viral zoonoses.


Assuntos
Quirópteros/virologia , Fezes/virologia , Metagenômica/métodos , Viroma/genética , Vírus/genética , Zoonoses/virologia , Adenoviridae/classificação , Adenoviridae/genética , Animais , Quirópteros/classificação , Reservatórios de Doenças/virologia , Variação Genética , Genoma Viral/genética , Hepevirus/classificação , Hepevirus/genética , Humanos , Coronavírus da Síndrome Respiratória do Oriente Médio/classificação , Coronavírus da Síndrome Respiratória do Oriente Médio/genética , Filogenia , Rotavirus/classificação , Rotavirus/genética , Análise de Sequência de DNA/métodos , Suíça , Vírus/classificação
17.
Curr Opin Virol ; 49: 52-57, 2021 08.
Artigo em Inglês | MEDLINE | ID: mdl-34049261

RESUMO

SARS-CoV-2 has been detected in more than 141 million people and caused more than 3 million deaths worldwide. To reduce the additional loss of millions of lives until natural immunity is reached, researchers have focused on the only known method to stop the COVID-19 pandemic: vaccines. The pandemic has propelled high-speed vaccine development, some based on novel technology previously not utilized in the vaccine field. The new technology opens new possibilities and comes with challenges because the long-term performance of the new platforms is unknown. Here we review the current leading vaccine candidates against COVID-19 and outline the advantages and disadvantages as well as the unknowns of each candidate.


Assuntos
Pesquisa Biomédica , Vacinas contra COVID-19/imunologia , COVID-19/prevenção & controle , SARS-CoV-2/imunologia , Adenoviridae/genética , Pesquisa Biomédica/estatística & dados numéricos , Pesquisa Biomédica/tendências , COVID-19/epidemiologia , Vacinas contra COVID-19/administração & dosagem , Vacinas contra COVID-19/efeitos adversos , Vacinas contra COVID-19/genética , Humanos , Mutação , SARS-CoV-2/genética , Vacinas de Produtos Inativados/administração & dosagem , Vacinas de Produtos Inativados/efeitos adversos , Vacinas de Produtos Inativados/genética , Vacinas de Produtos Inativados/imunologia , Vacinas de Subunidades/administração & dosagem , Vacinas de Subunidades/efeitos adversos , Vacinas de Subunidades/genética , Vacinas de Subunidades/imunologia , Vacinas Sintéticas/administração & dosagem , Vacinas Sintéticas/efeitos adversos , Vacinas Sintéticas/genética , Vacinas Sintéticas/imunologia
18.
Vaccine ; 39(26): 3498-3508, 2021 06 11.
Artigo em Inglês | MEDLINE | ID: mdl-34016474

RESUMO

Adenovirus infections are a major cause of epidemic keratoconjunctivitis (EKC), which can lead to corneal subepithelial infiltrates and multifocal corneal opacity. In the current study, we investigated the use of an E1/E3-deleted adenovirus serotype 5 (Ad5) vector as a vaccine administered intramuscularly (IM) or intranasally (IN) against subsequent challenges with a luciferase-expressing Ad5 (Ad5-Luci) vector via eyedrop. We evaluated the adaptive immune response to Ad5 vector vaccination and confirmed a robust polyfunctional CD8 T cell response in splenic cells. Neutralizing Ad5 antibodies were also measured in the sera of vaccinated mice as well as Ad5 antibody in the eye wash solutions. Upon challenge with Ad5-Luci vector 8 weeks post the primary immunization, transduction was significantly reduced by > 70% in the vaccinated mice, which was slightly better in IM- vs. that in IN-vaccinated animals. Resistance to subsequent challenge was observed 10 months post primary IM vaccination, with sustained reduction up to 60% in the Ad5-Luci vector transduction. Passive immunization of naive mice with antisera from IM to vaccinated mice subsequently challenged with the Ad5-Luci vector resulted in approximately 40% loss in transduction efficiency. Furthermore, the mice that received IM immunization with or without CD8 T cell depletion showed > 40% and 70% reductions, respectively, in Ad8 genomic copies after Ad8 topical challenge. We conclude that Ad-vector vaccination successfully induced an adaptive immune response that prevented subsequent Ad transduction in the cornea and conjunctiva-associated tissues in a mouse model of adenovirus keratoconjunctivitis, and that both cellular and humoral immunity play an important role in preventing Ad transduction.


Assuntos
Adenovírus Humanos , Ceratoconjuntivite , Adenoviridae/genética , Adenovírus Humanos/genética , Animais , Vetores Genéticos , Humanos , Ceratoconjuntivite/prevenção & controle , Camundongos , Vacinação
19.
Vaccine ; 39(27): 3560-3564, 2021 06 16.
Artigo em Inglês | MEDLINE | ID: mdl-34030897

RESUMO

Adenoviruses cause economically important diseases in vertebrates. Effective vaccines against adenoviral diseases are currently lacking. Here, we report a highly conserved epitopic region on hexon proteins of adenoviruses that generate a strong immune response when used as a virus-like-particle (VLP) vaccine, produced by inserting the epitopic region into the core protein of hepatitis B virus. For evaluation of its protective efficacy, the epitopic region from a representative adenovirus, fowl adenovirus serotype 4 (FAdV-4), was tested as a VLP vaccine which conferred 90% protection against challenge with a virulent FAdV-4 isolate in chickens. Importantly, such a high level of protection is not achieved when the epitopic region is employed as a part of a subunit vaccine. As the sequence and the structure of the epitopic region are highly conserved in hexon proteins of adenoviruses, the epitopic region could be employed as a promising VLP vaccine candidate against adenoviral diseases, in general.


Assuntos
Infecções por Adenoviridae , Vacinas contra Adenovirus , Doenças das Aves Domésticas , Adenoviridae/genética , Infecções por Adenoviridae/prevenção & controle , Infecções por Adenoviridae/veterinária , Animais , Proteínas do Capsídeo/genética , Galinhas , Epitopos , Doenças das Aves Domésticas/prevenção & controle
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