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1.
Curr Opin HIV AIDS ; 15(6): 351-358, 2020 11.
Artigo em Inglês | MEDLINE | ID: mdl-32969973

RESUMO

PURPOSE OF REVIEW: Coronavirus disease-19 (COVID-19) is a highly transmittable and pathogenic pneumonia-causing disease, which is caused by severe acute respiratory syndrome coronavirus-2, resulting in millions of deaths globally. Severe acute respiratory syndrome coronavirus-2 may coexist with human populations for a long time. Therefore, high-effective COVID-19 vaccines are an urgent need. RECENT FINDINGS: Vaccines help in the development of long-lasting humoral or cellular immunity, or both, by exposing individuals to antigens that induce an immunological response and memory prior to infections with live pathogens. New vaccine technologies, such as viral vectors and nucleic acid-based vaccines, which represent highly versatile technologies, may allow for faster vaccine manufacture and scale up production. SUMMARY: We summarized the recent progress made in relation to COVID-19 vaccine development using several promising technologies, with particular emphasis on advancements that are currently at the clinical trial stage.


Assuntos
Infecções por Coronavirus/prevenção & controle , Pandemias/prevenção & controle , Pneumonia Viral/prevenção & controle , Vacinas Virais/imunologia , Adenoviridae/genética , Infecções por Coronavirus/imunologia , Humanos , Vacinação , Vacinas Atenuadas/imunologia , Vacinas de DNA/imunologia , Vacinas de Produtos Inativados/imunologia , Vacinas Sintéticas/imunologia
2.
Cell ; 182(5): 1271-1283.e16, 2020 09 03.
Artigo em Inglês | MEDLINE | ID: mdl-32795413

RESUMO

There is an urgent need for vaccines against coronavirus disease 2019 (COVID-19) because of the ongoing SARS-CoV-2 pandemic. Among all approaches, a messenger RNA (mRNA)-based vaccine has emerged as a rapid and versatile platform to quickly respond to this challenge. Here, we developed a lipid nanoparticle-encapsulated mRNA (mRNA-LNP) encoding the receptor binding domain (RBD) of SARS-CoV-2 as a vaccine candidate (called ARCoV). Intramuscular immunization of ARCoV mRNA-LNP elicited robust neutralizing antibodies against SARS-CoV-2 as well as a Th1-biased cellular response in mice and non-human primates. Two doses of ARCoV immunization in mice conferred complete protection against the challenge of a SARS-CoV-2 mouse-adapted strain. Additionally, ARCoV is manufactured as a liquid formulation and can be stored at room temperature for at least 1 week. ARCoV is currently being evaluated in phase 1 clinical trials.


Assuntos
RNA Mensageiro/genética , RNA Viral/genética , Vacinas Sintéticas/imunologia , Vacinas Virais/imunologia , Animais , Anticorpos Neutralizantes/imunologia , Sítios de Ligação , Chlorocebus aethiops , Infecções por Coronavirus/genética , Infecções por Coronavirus/imunologia , Infecções por Coronavirus/prevenção & controle , Feminino , Células HEK293 , Células HeLa , Humanos , Imunogenicidade da Vacina , Injeções Intramusculares , Macaca fascicularis , Masculino , Camundongos , Camundongos Endogâmicos ICR , Nanopartículas/química , RNA Mensageiro/metabolismo , RNA Viral/metabolismo , Glicoproteína da Espícula de Coronavírus/química , Glicoproteína da Espícula de Coronavírus/genética , Glicoproteína da Espícula de Coronavírus/metabolismo , Células Th1/imunologia , Potência de Vacina , Vacinas Sintéticas/administração & dosagem , Vacinas Sintéticas/genética , Células Vero , Vacinas Virais/administração & dosagem , Vacinas Virais/genética
3.
Cell Host Microbe ; 28(3): 465-474.e4, 2020 09 09.
Artigo em Inglês | MEDLINE | ID: mdl-32798445

RESUMO

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused millions of human infections, and an effective vaccine is critical to mitigate coronavirus-induced disease 2019 (COVID-19). Previously, we developed a replication-competent vesicular stomatitis virus (VSV) expressing a modified form of the SARS-CoV-2 spike gene in place of the native glycoprotein gene (VSV-eGFP-SARS-CoV-2). Here, we show that vaccination with VSV-eGFP-SARS-CoV-2 generates neutralizing immune responses and protects mice from SARS-CoV-2. Immunization of mice with VSV-eGFP-SARS-CoV-2 elicits high antibody titers that neutralize SARS-CoV-2 and target the receptor binding domain that engages human angiotensin-converting enzyme-2 (ACE2). Upon challenge with a human isolate of SARS-CoV-2, mice that expressed human ACE2 and were immunized with VSV-eGFP-SARS-CoV-2 show profoundly reduced viral infection and inflammation in the lung, indicating protection against pneumonia. Passive transfer of sera from VSV-eGFP-SARS-CoV-2-immunized animals also protects naive mice from SARS-CoV-2 challenge. These data support development of VSV-SARS-CoV-2 as an attenuated, replication-competent vaccine against SARS-CoV-2.


Assuntos
Betacoronavirus , Infecções por Coronavirus/prevenção & controle , Pandemias/prevenção & controle , Pneumonia Viral/prevenção & controle , Vírus da Estomatite Vesicular Indiana/genética , Vacinas Virais/genética , Animais , Anticorpos Neutralizantes/sangue , Anticorpos Antivirais/sangue , Betacoronavirus/imunologia , Betacoronavirus/patogenicidade , Chlorocebus aethiops , Infecções por Coronavirus/genética , Infecções por Coronavirus/imunologia , Infecções por Coronavirus/virologia , Modelos Animais de Doenças , Vetores Genéticos , Proteínas de Fluorescência Verde/genética , Interações entre Hospedeiro e Microrganismos/imunologia , Humanos , Pulmão/imunologia , Pulmão/patologia , Pulmão/virologia , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Transgênicos , Peptidil Dipeptidase A/genética , Pneumonia Viral/imunologia , Pneumonia Viral/virologia , Receptores Virais/genética , Pesquisa Médica Translacional , Vacinas Sintéticas/genética , Vacinas Sintéticas/imunologia , Vacinas Sintéticas/farmacologia , Células Vero , Vírus da Estomatite Vesicular Indiana/imunologia , Vacinas Virais/imunologia , Vacinas Virais/farmacologia
4.
Nat Commun ; 11(1): 3523, 2020 07 09.
Artigo em Inglês | MEDLINE | ID: mdl-32647131

RESUMO

The spread of the SARS-CoV-2 into a global pandemic within a few months of onset motivates the development of a rapidly scalable vaccine. Here, we present a self-amplifying RNA encoding the SARS-CoV-2 spike protein encapsulated within a lipid nanoparticle (LNP) as a vaccine. We observe remarkably high and dose-dependent SARS-CoV-2 specific antibody titers in mouse sera, as well as robust neutralization of both a pseudo-virus and wild-type virus. Upon further characterization we find that the neutralization is proportional to the quantity of specific IgG and of higher magnitude than recovered COVID-19 patients. saRNA LNP immunizations induce a Th1-biased response in mice, and there is no antibody-dependent enhancement (ADE) observed. Finally, we observe high cellular responses, as characterized by IFN-γ production, upon re-stimulation with SARS-CoV-2 peptides. These data provide insight into the vaccine design and evaluation of immunogenicity to enable rapid translation to the clinic.


Assuntos
Anticorpos Neutralizantes/imunologia , Betacoronavirus/imunologia , Infecções por Coronavirus/prevenção & controle , Nanopartículas/química , Pandemias/prevenção & controle , Pneumonia Viral/prevenção & controle , Vacinas Virais/imunologia , Animais , Anticorpos Antivirais/sangue , Anticorpos Antivirais/metabolismo , Anticorpos Facilitadores/imunologia , Betacoronavirus/genética , Infecções por Coronavirus/imunologia , Infecções por Coronavirus/virologia , Citocinas/imunologia , Modelos Animais de Doenças , Humanos , Imunidade Celular , Imunoglobulina G/sangue , Camundongos , Camundongos Endogâmicos BALB C , Pneumonia Viral/imunologia , Pneumonia Viral/virologia , RNA Viral/imunologia , Glicoproteína da Espícula de Coronavírus/genética , Glicoproteína da Espícula de Coronavírus/imunologia , Vacinas Sintéticas/química , Vacinas Sintéticas/imunologia , Vacinas Virais/química
5.
PLoS Negl Trop Dis ; 14(7): e0008459, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-32667913

RESUMO

Rabies, caused by RNA viruses in the Genus Lyssavirus, is the most fatal of all infectious diseases. This neglected zoonosis remains a major public health problem in developing countries, causing the death of an estimated 25,000-159,000 people each year, with more than half of them in children. The high incidence of human rabies in spite of effective vaccines is mainly linked to the lack of compliance with the complicated administration schedule, inadequacies of the community public health system for local administration by the parenteral route and the overall costs of the vaccine. The goal of our work was the development of a simple, affordable and effective vaccine strategy to prevent human rabies virus infection. This next generation vaccine is based on a replication-defective chimpanzee adenovirus vector belonging to group C, ChAd155-RG, which encodes the rabies glycoprotein (G). We demonstrate here that a single dose of this vaccine induces protective efficacy in a murine model of rabies challenge and elicits strong and durable neutralizing antibody responses in vaccinated non-human primates. Importantly, we demonstrate that one dose of a commercial rabies vaccine effectively boosts the neutralizing antibody responses induced by ChAd155-RG in vaccinated monkeys, showing the compatibility of the novel vectored vaccine with the current post-exposure prophylaxis in the event of rabies virus exposure. Finally, we demonstrate that antibodies induced by ChAd155-RG can also neutralize European bat lyssaviruses 1 and 2 (EBLV-1 and EBLV-2) found in bat reservoirs.


Assuntos
Adenovirus dos Símios/genética , Vacinas Antirrábicas/imunologia , Raiva/prevenção & controle , Animais , Antígenos Virais , Feminino , Vetores Genéticos/genética , Humanos , Macaca fascicularis , Camundongos , Pan troglodytes/virologia , Profilaxia Pós-Exposição , Coelhos , Vírus da Raiva/genética , Vírus da Raiva/imunologia , Sorogrupo , Vacinação , Vacinas Sintéticas/imunologia , Zoonoses
6.
Int J Mol Sci ; 21(14)2020 Jul 20.
Artigo em Inglês | MEDLINE | ID: mdl-32698494

RESUMO

Single-stranded RNA viruses such as alphaviruses, flaviviruses, measles viruses and rhabdoviruses are characterized by their capacity of highly efficient self-amplification of RNA in host cells, which make them attractive vehicles for vaccine development. Particularly, alphaviruses and flaviviruses can be administered as recombinant particles, layered DNA/RNA plasmid vectors carrying the RNA replicon and even RNA replicon molecules. Self-amplifying RNA viral vectors have been used for high level expression of viral and tumor antigens, which in immunization studies have elicited strong cellular and humoral immune responses in animal models. Vaccination has provided protection against challenges with lethal doses of viral pathogens and tumor cells. Moreover, clinical trials have demonstrated safe application of RNA viral vectors and even promising results in rhabdovirus-based phase III trials on an Ebola virus vaccine. Preclinical and clinical applications of self-amplifying RNA viral vectors have proven efficient for vaccine development and due to the presence of RNA replicons, amplification of RNA in host cells will generate superior immune responses with significantly reduced amounts of RNA delivered. The need for novel and efficient vaccines has become even more evident due to the global COVID-19 pandemic, which has further highlighted the urgency in challenging emerging diseases.


Assuntos
Neoplasias/prevenção & controle , RNA Viral/genética , Vacinas Sintéticas/imunologia , Vacinas Virais/imunologia , Viroses/prevenção & controle , Animais , Vetores Genéticos/genética , Humanos , Camundongos , Neoplasias/virologia , Vacinação , Vírus/genética
8.
Vaccine ; 38(35): 5734-5739, 2020 07 31.
Artigo em Inglês | MEDLINE | ID: mdl-32653276

RESUMO

Several protein vaccine candidates are among the COVID-19 vaccines in development. The Brighton Collaboration Viral Vector Vaccines Safety Working Group (V3SWG) has prepared a standardized template to describe the key considerations for the benefit-risk assessment of protein vaccines. This will help key stakeholders to assess potential safety issues and understand the benefit-risk of such a vaccine platform. The structured and standardized assessment provided by the template would also help contribute to improved public acceptance and communication of licensed protein vaccines.


Assuntos
Vacinas Virais/efeitos adversos , Vacinas Virais/imunologia , Antígenos Virais/administração & dosagem , Antígenos Virais/efeitos adversos , Antígenos Virais/imunologia , Infecções por Coronavirus/imunologia , Infecções por Coronavirus/prevenção & controle , Humanos , Segurança do Paciente , Medição de Risco , Vacinas Sintéticas/administração & dosagem , Vacinas Sintéticas/efeitos adversos , Vacinas Sintéticas/imunologia , Proteínas Virais/administração & dosagem , Proteínas Virais/efeitos adversos , Proteínas Virais/imunologia , Vacinas Virais/administração & dosagem
9.
Nat Commun ; 11(1): 3545, 2020 07 15.
Artigo em Inglês | MEDLINE | ID: mdl-32669564

RESUMO

Group A Streptococcus (GAS) infection causes a range of diseases, but vaccine development is hampered by the high number of serotypes. Here, using reverse vaccinology the authors identify SPy_2191 as a cross-protective vaccine candidate. From 18 initially identified surface proteins, only SPy_2191 is conserved, surface-exposed and inhibits both GAS adhesion and invasion. SPy_2191 immunization in mice generates bactericidal antibodies resulting in opsonophagocytic killing of prevalent and invasive GAS serotypes of different geographical regions, including M1 and M49 (India), M3.1 (Israel), M1 (UK) and M1 (USA). Resident splenocytes show higher interferon-γ and tumor necrosis factor-α secretion upon antigen re-stimulation, suggesting activation of cell-mediated immunity. SPy_2191 immunization significantly reduces streptococcal load in the organs and confers ~76-92% protection upon challenge with invasive GAS serotypes. Further, it significantly suppresses GAS pharyngeal colonization in mice mucosal infection model. Our findings suggest that SPy_2191 can act as a universal vaccine candidate against GAS infections.


Assuntos
Proteínas de Bactérias/imunologia , Proteção Cruzada/imunologia , Infecções Estreptocócicas/prevenção & controle , Vacinas Estreptocócicas/imunologia , Streptococcus pyogenes/imunologia , Animais , Aderência Bacteriana/imunologia , Linhagem Celular , Clonagem Molecular , Modelos Animais de Doenças , Feminino , Humanos , Imunogenicidade da Vacina , Camundongos , Testes de Neutralização , Proteínas Recombinantes/administração & dosagem , Proteínas Recombinantes/imunologia , Sorogrupo , Infecções Estreptocócicas/microbiologia , Vacinas Estreptocócicas/administração & dosagem , Vacinas Sintéticas/administração & dosagem , Vacinas Sintéticas/imunologia
10.
Adv Virus Res ; 107: 383-416, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32711735

RESUMO

Since the end of 2019, the global COVID-19 outbreak has once again made coronaviruses a hot topic. Vaccines are hoped to be an effective way to stop the spread of the virus. However, there are no clinically approved vaccines available for coronavirus infections. Reverse genetics technology can realize the operation of RNA virus genomes at the DNA level and provide new ideas and strategies for the development of new vaccines. In this review, we systematically describe the role of reverse genetics technology in studying the effects of coronavirus proteins on viral virulence and innate immunity, cell and tissue tropism and antiviral drug screening. An efficient reverse genetics platform is useful for obtaining the ideal attenuated strain to prepare an attenuated live vaccine.


Assuntos
Betacoronavirus/imunologia , Infecções por Coronavirus/prevenção & controle , Pandemias/prevenção & controle , Pneumonia Viral/prevenção & controle , Vacinas Sintéticas/imunologia , Proteínas Virais/genética , Proteínas Virais/imunologia , Vacinas Virais/imunologia , Infecções por Coronavirus/imunologia , Genoma Viral/genética , Humanos , Pneumonia Viral/imunologia , RNA Viral/genética , Genética Reversa/métodos
11.
Paediatr Respir Rev ; 35: 43-49, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32653463

RESUMO

There is a strong consensus globally that a COVID-19 vaccine is likely the most effective approach to sustainably controlling the COVID-19 pandemic. An unprecedented research effort and global coordination has resulted in a rapid development of vaccine candidates and initiation of trials. Here, we review vaccine types, and progress with 10 vaccine candidates against SARS-CoV-2 - the virus that causes COVID-19 - currently undergoing early phase human trials. We also consider the many challenges of developing and deploying a new vaccine on a global scale, and recommend caution with respect to our expectations of the timeline that may be ahead.


Assuntos
Betacoronavirus/imunologia , Infecções por Coronavirus/prevenção & controle , Pandemias/prevenção & controle , Pneumonia Viral/prevenção & controle , Vacinas de DNA/uso terapêutico , Vacinas Sintéticas/uso terapêutico , Vacinas Virais/uso terapêutico , Ensaios Clínicos como Assunto , Infecções por Coronavirus/imunologia , Desenvolvimento de Medicamentos , Humanos , Coronavírus da Síndrome Respiratória do Oriente Médio/imunologia , Vírus da SARS/imunologia , Vacinas de DNA/imunologia , Vacinas Sintéticas/imunologia , Vacinas Virais/imunologia
12.
Exp Parasitol ; 216: 107944, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32619431

RESUMO

Evaluation of the murine isotype antibodies is essential in subunit vaccine development because inbred mouse strains with diverse genetic backgrounds respond different to recombinant proteins. In this regard, the main goal of this study was to measuring and comparing the profile of IgG isotype responses in C57BL/6 mice. For this purpose, the extracellular region of plasmodium vivax thrombospondin-related adhesive protein (PvTRAP) gene was expressed in Escherichia coli Rosetta (DE3)-pET23a. Then, the recombinant PvTRAP alone or emulsified with Freund's complete adjuvant were applied for immunization of the C57BL/6 mice. The role of antibodies and cellular immune responses induced by recombinant PvTRAP were evaluated. The results showed the level of anti-rPvTRAP IgG2c was significantly higher than IgG2a in the groups that received rPvTRAP alone (mean OD490 = 0.798 ± 0.12 and 0.39 ± 0.1, respectively) and emulsified with CFA/IFA (mean OD490 = 1.48 ± 0.07 and 0.605 ± 0.13, respectively; P < 0.05, independent sample t-test). Additionally, the immunized mice with rPvTRAP and rPvTRAP + CFA/IFA had an intermediate-avidity IgG2a antibody but high-avidity IgG2c antibody as well as the mean of serum antibody titers results exhibited that in both rPvTRAP and rPvTRAP + CFA/IFA mouse groups, IgG2a end-point titer (1:3200 and 1:25,600, respectively) was noteworthy lower than IgG2c (1:25,600 and 1:102,400, respectively). Moreover, the results revealed the eliciting significant levels of IFN-γ (P < 0.05, independent sample t-test) and no detectable level of IL-4 in the mouse groups received rPvTRAP alone and emulsified with CFA/IFA as compared to the mouse control groups. In general, our results showed that for correctly interpreting of Th1 immune responses in C57BL/6 mouse strain it is critical to measure IgG2c instead of IgG2a along with IFN-γ.


Assuntos
Imunoglobulina G/sangue , Plasmodium vivax/imunologia , Proteínas de Protozoários/imunologia , Vacinas Protozoárias/imunologia , Células Th1/imunologia , Células Th2/imunologia , Animais , Afinidade de Anticorpos , Dicroísmo Circular , Feminino , Imunofluorescência , Imunoglobulina G/classificação , Interferon gama/análise , Interleucina-4/análise , Linfócitos/imunologia , Camundongos , Camundongos Endogâmicos C57BL , Proteínas Recombinantes/imunologia , Vacinas de Subunidades/imunologia , Vacinas Sintéticas/imunologia
13.
Comput Biol Med ; 121: 103749, 2020 06.
Artigo em Inglês | MEDLINE | ID: mdl-32568687

RESUMO

This paper continues a recent study of the spike protein sequence of the COVID-19 virus (SARS-CoV-2). It is also in part an introductory review to relevant computational techniques for tackling viral threats, using COVID-19 as an example. Q-UEL tools for facilitating access to knowledge and bioinformatics tools were again used for efficiency, but the focus in this paper is even more on the virus. Subsequence KRSFIEDLLFNKV of the S2' spike glycoprotein proteolytic cleavage site continues to appear important. Here it is shown to be recognizable in the common cold coronaviruses, avian coronaviruses and possibly as traces in the nidoviruses of reptiles and fish. Its function or functions thus seem important to the coronaviruses. It might represent SARS-CoV-2 Achilles' heel, less likely to acquire resistance by mutation, as has happened in some early SARS vaccine studies discussed in the previous paper. Preliminary conformational analysis of the receptor (ACE2) binding site of the spike protein is carried out suggesting that while it is somewhat conserved, it appears to be more variable than KRSFIEDLLFNKV. However compounds like emodin that inhibit SARS entry, apparently by binding ACE2, might also have functions at several different human protein binding sites. The enzyme 11ß-hydroxysteroid dehydrogenase type 1 is again argued to be a convenient model pharmacophore perhaps representing an ensemble of targets, and it is noted that it occurs both in lung and alimentary tract. Perhaps it benefits the virus to block an inflammatory response by inhibiting the dehydrogenase, but a fairly complex web involves several possible targets.


Assuntos
Betacoronavirus , Infecções por Coronavirus/tratamento farmacológico , Infecções por Coronavirus/prevenção & controle , Pandemias/prevenção & controle , Pneumonia Viral/tratamento farmacológico , Pneumonia Viral/prevenção & controle , Glicoproteína da Espícula de Coronavírus/química , Vacinas Virais/imunologia , Sequência de Aminoácidos , Animais , Antivirais/farmacologia , Betacoronavirus/química , Betacoronavirus/genética , Betacoronavirus/imunologia , Sítios de Ligação , Biologia Computacional , Coronavirus/química , Coronavirus/genética , Coronavirus/imunologia , Infecções por Coronavirus/genética , Infecções por Coronavirus/imunologia , Infecções por Coronavirus/virologia , Desenho de Fármacos , Farmacorresistência Viral/genética , Interações entre Hospedeiro e Microrganismos/genética , Interações entre Hospedeiro e Microrganismos/imunologia , Humanos , Modelos Moleculares , Mutação , Peptidomiméticos/farmacologia , Peptidil Dipeptidase A/química , Peptidil Dipeptidase A/genética , Peptidil Dipeptidase A/metabolismo , Pneumonia Viral/virologia , Homologia de Sequência de Aminoácidos , Glicoproteína da Espícula de Coronavírus/genética , Glicoproteína da Espícula de Coronavírus/imunologia , Vacinas Sintéticas/genética , Vacinas Sintéticas/imunologia , Vacinas Virais/genética
14.
Int J Biol Macromol ; 162: 820-837, 2020 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-32599237

RESUMO

SARS-CoV-2 is the deadly virus behind COVID-19, the disease that went on to ravage the world and caused the biggest pandemic 21st century has witnessed so far. On the face of ongoing death and destruction, the urgent need for the discovery of a vaccine against the virus is paramount. This study resorted to the emerging discipline of immunoinformatics in order to design a multi-epitope mRNA vaccine against the spike glycoprotein of SARS-CoV-2. Various immunoinformatics tools were utilized to predict T and B lymphocyte epitopes. The epitopes were channeled through a filtering pipeline comprised of antigenicity, toxicity, allergenicity, and cytokine inducibility evaluation with the goal of selecting epitopes capable of generating both T and B cell-mediated immune responses. Molecular docking simulation between the epitopes and their corresponding MHC molecules was carried out. 13 epitopes, a highly immunogenic adjuvant, elements for proper sub-cellular trafficking, a secretion booster, and appropriate linkers were combined for constructing the vaccine. The vaccine was found to be antigenic, almost neutral at physiological pH, non-toxic, non-allergenic, capable of generating a robust immune response and had a decent worldwide population coverage. Based on these parameters, this design can be considered a promising choice for a vaccine against SARS-CoV-2.


Assuntos
Infecções por Coronavirus/prevenção & controle , Pandemias/prevenção & controle , Pneumonia Viral/prevenção & controle , RNA Mensageiro/imunologia , Vacinas Virais/imunologia , Betacoronavirus/imunologia , Infecções por Coronavirus/genética , Infecções por Coronavirus/imunologia , Infecções por Coronavirus/virologia , Desenho de Fármacos , Epitopos de Linfócito B/química , Epitopos de Linfócito B/imunologia , Epitopos de Linfócito T/química , Epitopos de Linfócito T/imunologia , Humanos , Imunogenicidade da Vacina , Simulação de Acoplamento Molecular , Pneumonia Viral/imunologia , Pneumonia Viral/virologia , Análise de Sequência de Proteína , Glicoproteína da Espícula de Coronavírus/química , Glicoproteína da Espícula de Coronavírus/imunologia , Vacinas Sintéticas/química , Vacinas Sintéticas/genética , Vacinas Sintéticas/imunologia , Vacinas Virais/química , Vacinas Virais/genética
15.
Mol Immunol ; 124: 70-82, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32540517

RESUMO

Several vaccine candidates have been introduced for immunization against Pseudomonas aeruginosa strains. Despite extensive efforts in recent decades, there is no accurate immunogenic candidate against this pathogen in the market yet. Due to the rapid increase in several drug-resistant strains, P. aeruginosa has caused various health concerns worldwide. It encodes many specific virulence features, which can be used as an appropriate vaccine candidate. The primary stage of the pathogenesis of P. aeruginosa is the expression of many dynamic adhesive molecules, such as type IV pili (T4P), which acts as a principal colonization factor. It has been confirmed that three different subtypes of T4P, including type IVa (T4aP), type IVb (T4bP) and tight adherence (Tad) pili are expressed by P. aeruginosa. The IVa fimbriae type is almost the main cause of challenges to design an effective pili based-immunotherapy method. Nevertheless, in terms of heterogeneity, variability and hidden conserved binding site of T4aP, this attitude has been remained controversial and there is no permitted human study based on IVa pilin commercially. The engineered synthetic peptide-based vaccines are highly talented to mimic the target. In this research, for the first time, some dominant immunogenic features of the Flp protein, such as both B- and T-cell-associated epitopes, presence of IgE-associated epitopes, solvent-accessible surface area were evaluated by analytical immunoinformatics methods. In addition, we designed the engineered Flp pilin as an effective immunogenic substance against several clinically important P. aeruginosa strains. Moreover, by practical active immunization approaches, the humoral and cellular immune response against the extremely conserved region of the engineered synthetic Flp (EFlp) formulated in Montanide ISA 266 compared to the control group. The results of active immunization against EFlp significantly signified that EFlp-Montanide ISA 266 (EFLP-M) strongly could induce both humoral and cellular immune responses. We concluded that Flp pilin has therapeutic potential against numerous clinically significant P. aeruginosa strains and can be served as a novel immunogen for further investigations for development of effective immunotherapy methods against P. aeruginosa as a dexterous pathogen.


Assuntos
Proteínas de Bactérias/imunologia , Vacinas contra Pseudomonas/imunologia , Pseudomonas aeruginosa/imunologia , Animais , Biologia Computacional , Epitopos de Linfócito B/imunologia , Epitopos de Linfócito T/imunologia , Feminino , Epitopos Imunodominantes/imunologia , Camundongos , Camundongos Endogâmicos BALB C , Infecções por Pseudomonas/prevenção & controle , Vacinação , Vacinas Sintéticas/imunologia
18.
Immunology ; 160(3): 223-232, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-32460358

RESUMO

Since the first World Health Organization notification on 31 December 2019, coronavirus disease 2019 (COVID-19), the respiratory disease caused by the coronavirus severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), has been responsible for over four million confirmed infections and almost 300 000 deaths worldwide. The pandemic has led to over half of the world's population living under lockdown conditions. To allow normal life to resume, public health interventions will be needed to prevent further waves of infections as lockdown measures are lifted. As one of the most effective countermeasures against infectious diseases, an efficacious vaccine is considered crucial to containing the COVID-19 pandemic. Following the publication of the genome sequence of SARS-CoV-2, vaccine development has accelerated at an unprecedented pace across the world. Here we review the different platforms employed to develop vaccines, the standard timelines of development and how they can be condensed in a pandemic situation. We focus on vaccine development in the UK and vaccines that have entered clinical trials around the world.


Assuntos
Vacinas Virais , Animais , Ensaios Clínicos como Assunto , Infecções por Coronavirus/epidemiologia , Infecções por Coronavirus/prevenção & controle , Humanos , Pandemias , Pneumonia Viral/epidemiologia , Subunidades Proteicas/imunologia , Reino Unido , Vacinas Atenuadas/imunologia , Vacinas de DNA/imunologia , Vacinas Sintéticas/imunologia
19.
mBio ; 11(2)2020 04 07.
Artigo em Inglês | MEDLINE | ID: covidwho-38355

RESUMO

Middle East respiratory syndrome coronavirus (MERS-CoV) can cause severe and fatal acute respiratory disease in humans and remains endemic in the Middle East since first being identified in 2012. There are currently no approved vaccines or therapies available for MERS-CoV. In this study, we evaluated parainfluenza virus 5 (PIV5)-based vaccine expressing the MERS-CoV envelope spike protein (PIV5/MERS-S) in a human DPP4 knockin C57BL/6 congenic mouse model (hDPP4 KI). Following a single-dose intranasal immunization, PIV5-MERS-S induced neutralizing antibody and robust T cell responses in hDPP4 KI mice. A single intranasal administration of 104 PFU PIV5-MERS-S provided complete protection against a lethal challenge with mouse-adapted MERS-CoV (MERSMA6.1.2) and improved virus clearance in the lung. In comparison, single-dose intramuscular immunization with 106 PFU UV-inactivated MERSMA6.1.2 mixed with Imject alum provided protection to only 25% of immunized mice. Intriguingly, an influx of eosinophils was observed only in the lungs of mice immunized with inactivated MERS-CoV, suggestive of a hypersensitivity-type response. Overall, our study indicated that PIV5-MERS-S is a promising effective vaccine candidate against MERS-CoV infection.IMPORTANCE MERS-CoV causes lethal infection in humans, and there is no vaccine. Our work demonstrates that PIV5 is a promising vector for developing a MERS vaccine. Furthermore, success of PIV5-based MERS vaccine can be employed to develop a vaccine for emerging CoVs such as SARS-CoV-2, which causes COVID-19.


Assuntos
Infecções por Coronavirus/prevenção & controle , Glicoproteína da Espícula de Coronavírus/genética , Glicoproteína da Espícula de Coronavírus/imunologia , Vacinas Virais/genética , Vacinas Virais/imunologia , Administração Intranasal , Animais , Anticorpos Antivirais/sangue , Infecções por Coronavirus/imunologia , Infecções por Coronavirus/mortalidade , Modelos Animais de Doenças , Imunização , Camundongos , Camundongos Endogâmicos C57BL , Vírus da Parainfluenza 5/genética , Vacinas Sintéticas/administração & dosagem , Vacinas Sintéticas/genética , Vacinas Sintéticas/imunologia
20.
mBio ; 11(2)2020 04 07.
Artigo em Inglês | MEDLINE | ID: mdl-32265331

RESUMO

Middle East respiratory syndrome coronavirus (MERS-CoV) can cause severe and fatal acute respiratory disease in humans and remains endemic in the Middle East since first being identified in 2012. There are currently no approved vaccines or therapies available for MERS-CoV. In this study, we evaluated parainfluenza virus 5 (PIV5)-based vaccine expressing the MERS-CoV envelope spike protein (PIV5/MERS-S) in a human DPP4 knockin C57BL/6 congenic mouse model (hDPP4 KI). Following a single-dose intranasal immunization, PIV5-MERS-S induced neutralizing antibody and robust T cell responses in hDPP4 KI mice. A single intranasal administration of 104 PFU PIV5-MERS-S provided complete protection against a lethal challenge with mouse-adapted MERS-CoV (MERSMA6.1.2) and improved virus clearance in the lung. In comparison, single-dose intramuscular immunization with 106 PFU UV-inactivated MERSMA6.1.2 mixed with Imject alum provided protection to only 25% of immunized mice. Intriguingly, an influx of eosinophils was observed only in the lungs of mice immunized with inactivated MERS-CoV, suggestive of a hypersensitivity-type response. Overall, our study indicated that PIV5-MERS-S is a promising effective vaccine candidate against MERS-CoV infection.IMPORTANCE MERS-CoV causes lethal infection in humans, and there is no vaccine. Our work demonstrates that PIV5 is a promising vector for developing a MERS vaccine. Furthermore, success of PIV5-based MERS vaccine can be employed to develop a vaccine for emerging CoVs such as SARS-CoV-2, which causes COVID-19.


Assuntos
Infecções por Coronavirus/prevenção & controle , Glicoproteína da Espícula de Coronavírus/genética , Glicoproteína da Espícula de Coronavírus/imunologia , Vacinas Virais/genética , Vacinas Virais/imunologia , Administração Intranasal , Animais , Anticorpos Antivirais/sangue , Infecções por Coronavirus/imunologia , Infecções por Coronavirus/mortalidade , Modelos Animais de Doenças , Imunização , Camundongos , Camundongos Endogâmicos C57BL , Vírus da Parainfluenza 5/genética , Vacinas Sintéticas/administração & dosagem , Vacinas Sintéticas/genética , Vacinas Sintéticas/imunologia
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