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1.
Sci Rep ; 10(1): 16219, 2020 10 01.
Artigo em Inglês | MEDLINE | ID: mdl-33004978

RESUMO

COVID-19 pandemic has resulted in 16,114,449 cases with 646,641 deaths from the 217 countries, or territories as on July 27th 2020. Due to multifaceted issues and challenges in the implementation of the safety and preventive measures, inconsistent coordination between societies-governments and most importantly lack of specific vaccine to SARS-CoV-2, the spread of the virus that initially emerged at Wuhan is still uprising after taking a heavy toll on human life. In the present study, we mapped immunogenic epitopes present on the four structural proteins of SARS-CoV-2 and we designed a multi-epitope peptide based vaccine that, demonstrated a high immunogenic response with a vast application on world's human population. On codon optimization and in-silico cloning, we found that candidate vaccine showed high expression in E. coli and immune simulation resulted in inducing a high level of both B-cell and T-cell mediated immunity. The results predicted that exposure of vaccine by administrating three injections significantly subsidized the antigen growth in the system. The proposed candidate vaccine found promising by yielding desired results and hence, should be validated by practical experimentations for its functioning and efficacy to neutralize SARS-CoV-2.


Assuntos
Epitopos/imunologia , Simulação de Acoplamento Molecular , Vacinas de Subunidades/imunologia , Vacinas Virais/imunologia , Complexo Antígeno-Anticorpo/química , Complexo Antígeno-Anticorpo/imunologia , Antígenos Virais/imunologia , Linfócitos B/imunologia , Infecções por Coronavirus/imunologia , Infecções por Coronavirus/prevenção & controle , Epitopos/química , Antígenos HLA/química , Antígenos HLA/imunologia , Humanos , Imunogenicidade da Vacina , Proteínas do Nucleocapsídeo/química , Proteínas do Nucleocapsídeo/imunologia , Glicoproteína da Espícula de Coronavírus/química , Glicoproteína da Espícula de Coronavírus/imunologia , Linfócitos T/imunologia , Receptores Toll-Like/imunologia , Vacinas de Subunidades/química , Proteínas da Matriz Viral/química , Proteínas da Matriz Viral/imunologia , Vacinas Virais/química
2.
Front Immunol ; 11: 2008, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33013857

RESUMO

Coronavirus disease (COVID-19), caused by the virus SARS-CoV-2, is already responsible for more than 4.3 million confirmed cases and 295,000 deaths worldwide as of May 15, 2020. Ongoing efforts to control the pandemic include the development of peptide-based vaccines and diagnostic tests. In these approaches, HLA allelic diversity plays a crucial role. Despite its importance, current knowledge of HLA allele frequencies in South America is very limited. In this study, we have performed a literature review of datasets reporting HLA frequencies of South American populations, available in scientific literature and/or in the Allele Frequency Net Database. This allowed us to enrich the current scenario with more than 12.8 million data points. As a result, we are presenting updated HLA allelic frequencies based on country, including 91 alleles that were previously thought to have frequencies either under 5% or of an unknown value. Using alleles with an updated frequency of at least ≥5% in any South American country, we predicted epitopes in SARS-CoV-2 proteins using NetMHCpan (I and II) and MHC flurry. Then, the best predicted epitopes (class-I and -II) were selected based on their binding to South American alleles (Coverage Score). Class II predicted epitopes were also filtered based on their three-dimensional exposure. We obtained 14 class-I and four class-II candidate epitopes with experimental evidence (reported in the Immune Epitope Database and Analysis Resource), having good coverage scores for South America. Additionally, we are presenting 13 HLA-I and 30 HLA-II novel candidate epitopes without experimental evidence, including 16 class-II candidates in highly exposed conserved areas of the NTD and RBD regions of the Spike protein. These novel candidates have even better coverage scores for South America than those with experimental evidence. Finally, we show that recent similar studies presenting candidate epitopes also predicted some of our candidates but discarded them in the selection process, resulting in candidates with suboptimal coverage for South America. In conclusion, the candidate epitopes presented provide valuable information for the development of epitope-based strategies against SARS-CoV-2, such as peptide vaccines and diagnostic tests. Additionally, the updated HLA allelic frequencies provide a better representation of South America and may impact different immunogenetic studies.


Assuntos
Betacoronavirus/imunologia , Infecções por Coronavirus/epidemiologia , Infecções por Coronavirus/imunologia , Epitopos de Linfócito T/imunologia , Frequência do Gene , Antígenos HLA/genética , Pneumonia Viral/epidemiologia , Pneumonia Viral/imunologia , Proteínas do Envelope Viral/imunologia , Alelos , Sequência de Aminoácidos , Infecções por Coronavirus/prevenção & controle , Infecções por Coronavirus/virologia , Variação Genética , Humanos , Pandemias/prevenção & controle , Pneumonia Viral/prevenção & controle , Pneumonia Viral/virologia , América do Sul/epidemiologia , Vacinas de Subunidades/imunologia , Vacinas Virais/imunologia
3.
Front Immunol ; 11: 2130, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33013898

RESUMO

In the last decades, a number of infectious viruses have emerged from wildlife or re-emerged, generating serious threats to the global health and to the economy worldwide. Ebola and Marburg hemorrhagic fevers, Lassa fever, Dengue fever, Yellow fever, West Nile fever, Zika, and Chikungunya vector-borne diseases, Swine flu, Severe acute respiratory syndrome (SARS), Middle East respiratory syndrome (MERS), and the recent Coronavirus disease 2019 (COVID-19) are examples of zoonoses that have spread throughout the globe with such a significant impact on public health that the scientific community has been called for a rapid intervention in preventing and treating emerging infections. Vaccination is probably the most effective tool in helping the immune system to activate protective responses against pathogens, reducing morbidity and mortality, as proven by historical records. Under health emergency conditions, new and alternative approaches in vaccine design and development are imperative for a rapid and massive vaccination coverage, to manage a disease outbreak and curtail the epidemic spread. This review gives an update on the current vaccination strategies for some of the emerging/re-emerging viruses, and discusses challenges and hurdles to overcome for developing efficacious vaccines against future pathogens.


Assuntos
Betacoronavirus/imunologia , Doenças Transmissíveis Emergentes/prevenção & controle , Doenças Transmissíveis Emergentes/virologia , Infecções por Coronavirus/prevenção & controle , Pandemias/prevenção & controle , Pneumonia Viral/prevenção & controle , Vacinação , Vacinas Virais/imunologia , Animais , Anticorpos Facilitadores/imunologia , Infecções por Coronavirus/imunologia , Infecções por Coronavirus/terapia , Infecções por Coronavirus/virologia , Reações Cruzadas/imunologia , Humanos , Imunização Passiva , Pneumonia Viral/terapia , Pneumonia Viral/virologia , Vacinas Atenuadas/imunologia , Vacinas de DNA/imunologia , Vacinas de Produtos Inativados/imunologia , Vacinas de Subunidades/imunologia
4.
J Immunol Res ; 2020: 2837670, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32964056

RESUMO

The novel coronavirus disease (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has previously never been identified with humans, thereby creating devastation in public health. The need for an effective vaccine to curb this pandemic cannot be overemphasized. In view of this, we designed a subcomponent antigenic peptide vaccine targeting the N-terminal (NT) and C-terminal (CT) RNA binding domains of the nucleocapsid protein that aid in viral replication. Promising antigenic B cell and T cell epitopes were predicted using computational pipelines. The peptides "RIRGGDGKMKDL" and "AFGRRGPEQTQGNFG" were the B cell linear epitopes with good antigenic index and nonallergenic property. Two CD8+ and Three CD4+ T cell epitopes were also selected considering their safe immunogenic profiling such as allergenicity, antigen level conservancy, antigenicity, peptide toxicity, and putative restrictions to a number of MHC-I and MHC-II alleles. With these selected epitopes, a nonallergenic chimeric peptide vaccine incapable of inducing a type II hypersensitivity reaction was constructed. The molecular interaction between the Toll-like receptor-5 (TLR5) which was triggered by the vaccine was analyzed by molecular docking and scrutinized using dynamics simulation. Finally, in silico cloning was performed to ensure the expression and translation efficiency of the vaccine, utilizing the pET-28a vector. This research, therefore, provides a guide for experimental investigation and validation.


Assuntos
Betacoronavirus/imunologia , Infecções por Coronavirus/prevenção & controle , Proteínas do Nucleocapsídeo/imunologia , Nucleocapsídeo/imunologia , Pandemias/prevenção & controle , Pneumonia Viral/prevenção & controle , Vacinas Virais/imunologia , Linfócitos T CD4-Positivos/imunologia , Linfócitos T CD8-Positivos/imunologia , Epitopos de Linfócito B/genética , Epitopos de Linfócito B/imunologia , Epitopos de Linfócito T/genética , Epitopos de Linfócito T/imunologia , Humanos , Simulação de Acoplamento Molecular , Simulação de Dinâmica Molecular , Proteínas do Nucleocapsídeo/metabolismo , Proteínas com Motivo de Reconhecimento de RNA/imunologia , Motivos de Ligação ao RNA/imunologia , Receptor 5 Toll-Like/metabolismo , Vacinas Atenuadas/imunologia , Vacinas de Subunidades/imunologia
5.
Infect Dis Poverty ; 9(1): 132, 2020 Sep 16.
Artigo em Inglês | MEDLINE | ID: mdl-32938504

RESUMO

BACKGROUND: Coronavirus disease 2019 (COVID-19) linked with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) cause severe illness and life-threatening pneumonia in humans. The current COVID-19 pandemic demands an effective vaccine to acquire protection against the infection. Therefore, the present study was aimed to design a multiepitope-based subunit vaccine (MESV) against COVID-19. METHODS: Structural proteins (Surface glycoprotein, Envelope protein, and Membrane glycoprotein) of SARS-CoV-2 are responsible for its prime functions. Sequences of proteins were downloaded from GenBank and several immunoinformatics coupled with computational approaches were employed to forecast B- and T- cell epitopes from the SARS-CoV-2 highly antigenic structural proteins to design an effective MESV. RESULTS: Predicted epitopes suggested high antigenicity, conserveness, substantial interactions with the human leukocyte antigen (HLA) binding alleles, and collective global population coverage of 88.40%. Taken together, 276 amino acids long MESV was designed by connecting 3 cytotoxic T lymphocytes (CTL), 6 helper T lymphocyte (HTL) and 4 B-cell epitopes with suitable adjuvant and linkers. The MESV construct was non-allergenic, stable, and highly antigenic. Molecular docking showed a stable and high binding affinity of MESV with human pathogenic toll-like receptors-3 (TLR3). Furthermore, in silico immune simulation revealed significant immunogenic response of MESV. Finally, MEV codons were optimized for its in silico cloning into the Escherichia coli K-12 system, to ensure its increased expression. CONCLUSION: The MESV developed in this study is capable of generating immune response against COVID-19. Therefore, if designed MESV further investigated experimentally, it would be an effective vaccine candidate against SARS-CoV-2 to control and prevent COVID-19.


Assuntos
Betacoronavirus/imunologia , Infecções por Coronavirus/prevenção & controle , Epitopos de Linfócito B/imunologia , Epitopos de Linfócito T/imunologia , Pandemias/prevenção & controle , Pneumonia Viral/prevenção & controle , Vacinas Virais/imunologia , Infecções por Coronavirus/genética , Infecções por Coronavirus/imunologia , Epitopos de Linfócito B/química , Epitopos de Linfócito B/genética , Epitopos de Linfócito T/química , Epitopos de Linfócito T/genética , Humanos , Imunogenicidade da Vacina/imunologia , Simulação de Acoplamento Molecular , Pneumonia Viral/imunologia , Análise de Sequência de Proteína , Glicoproteína da Espícula de Coronavírus/química , Glicoproteína da Espícula de Coronavírus/genética , Glicoproteína da Espícula de Coronavírus/imunologia , Receptor 3 Toll-Like/química , Receptor 3 Toll-Like/genética , Receptor 3 Toll-Like/imunologia , Vacinas de Subunidades/química , Vacinas de Subunidades/genética , Vacinas de Subunidades/imunologia , Vacinologia/métodos , Proteínas da Matriz Viral/química , Proteínas da Matriz Viral/genética , Proteínas da Matriz Viral/imunologia , Vacinas Virais/química , Vacinas Virais/genética
6.
Sheng Wu Gong Cheng Xue Bao ; 36(7): 1314-1322, 2020 Jul 25.
Artigo em Chinês | MEDLINE | ID: mdl-32748589

RESUMO

To screen the best genotypeⅠJapanese encephalitis virus subunit vaccine candidate antigens, the prMEIII gene, the polytope gene and the prMEIII-polytope fusion gene of the GenotypeⅠJapanese encephalitis virus GS strain were cloned into prokaryotic expression vector pET-30a. The recombinant proteins were obtained after the induction and purification. The prepared recombinant proteins were immunized to mice, and the immunogenicity of the subunit vaccine candidate antigens was evaluated through monitoring the humoral immune response by ELISA, detecting the neutralizing antibody titer by plaque reduction neutralization test, and testing the cell-mediated immune response by lymphocyte proliferation assay and cytokine profiling. The recombinant proteins with the molecular weights of 35 (prMEIII), 28 (polytope antigen) and 57 kDa (prMEIII-polytope) induced strong humoral and cellular immune responses in mice. Compared with prMEIII-polytope and polytope proteins, the prMEIII protein induced a significant expression of IL-2 and IFN-γ (P<0.05) and the significant lymphoproliferation of splenocytes (P<0.05). The neutralizing antibody titer induced by the prMEIII protein was close to that induced by the commercial attenuated vaccine SA14-14-2 (P>0.05). The study suggests that the prMEIII protein can be used for the development of the Japanese encephalitis virus subunit vaccine.


Assuntos
Vírus da Encefalite Japonesa (Espécie) , Encefalite Japonesa , Vacinas Virais , Animais , Anticorpos Antivirais/sangue , Antígenos Virais/imunologia , Vírus da Encefalite Japonesa (Espécie)/imunologia , Encefalite Japonesa/imunologia , Encefalite Japonesa/prevenção & controle , Imunogenicidade da Vacina , Camundongos , Camundongos Endogâmicos BALB C , Vacinas de Subunidades/imunologia , Vacinas Virais/imunologia
7.
Front Immunol ; 11: 1784, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32849643

RESUMO

COVID-19 has recently become the most serious threat to public health, and its prevalence has been increasing at an alarming rate. The incubation period for the virus is ~1-14 days and all age groups may be susceptible to a fatality rate of about 5.9%. COVID-19 is caused by a novel single-stranded, positive (+) sense RNA beta coronavirus. The development of a vaccine for SARS-CoV-2 is an urgent need worldwide. Immunoinformatics approaches are both cost-effective and convenient, as in silico predictions can reduce the number of experiments needed. In this study, with the aid of immunoinformatics tools, we tried to design a multi-epitope vaccine that can be used for the prevention and treatment of COVID-19. The epitopes were computed by using B cells, cytotoxic T lymphocytes (CTL), and helper T lymphocytes (HTL) base on the proteins of SARS-CoV-2. A vaccine was devised by fusing together the B cell, HTL, and CTL epitopes with linkers. To enhance the immunogenicity, the ß-defensin (45 mer) amino acid sequence, and pan-HLA DR binding epitopes (13aa) were adjoined to the N-terminal of the vaccine with the help of the EAAAK linker. To enable the intracellular delivery of the modeled vaccine, a TAT sequence (11aa) was appended to C-terminal. Linkers play vital roles in producing an extended conformation (flexibility), protein folding, and separation of functional domains, and therefore, make the protein structure more stable. The secondary and three-dimensional (3D) structure of the final vaccine was then predicted. Furthermore, the complex between the final vaccine and immune receptors (toll-like receptor-3 (TLR-3), major histocompatibility complex (MHC-I), and MHC-II) were evaluated by molecular docking. Lastly, to confirm the expression of the designed vaccine, the mRNA of the vaccine was enhanced with the aid of the Java Codon Adaptation Tool, and the secondary structure was generated from Mfold. Then we performed in silico cloning. The final vaccine requires experimental validation to determine its safety and efficacy in controlling SARS-CoV-2 infections.


Assuntos
Betacoronavirus/química , Biologia Computacional/métodos , Infecções por Coronavirus/prevenção & controle , Epitopos de Linfócito B/imunologia , Epitopos de Linfócito T/imunologia , Pandemias/prevenção & controle , Pneumonia Viral/prevenção & controle , Proteínas Virais/imunologia , Vacinas Virais/imunologia , Sequência de Aminoácidos , Infecções por Coronavirus/virologia , Antígenos HLA-DR/imunologia , Humanos , Imunogenicidade da Vacina , Simulação de Acoplamento Molecular , Pneumonia Viral/virologia , Dobramento de Proteína , Estrutura Terciária de Proteína , Linfócitos T Citotóxicos/imunologia , Linfócitos T Auxiliares-Indutores/imunologia , Vacinas de Subunidades/imunologia , beta-Defensinas/imunologia
8.
J Med Microbiol ; 69(9): 1183-1196, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32812860

RESUMO

Introduction. PCV2 is a DNA virus that exists widely in pigs and has caused great economic losses to the pig industry worldwide. In the existing commercial PCV2 enzyme-linked immunosorbent assay (ELISA) kits both natural infection with PCV2 and vaccine immunization produce results that are positive for PCV2 Cap antibodies and therefore they cannot diagnose PCV2 infection in immunized pig farms.Aim. To establish a PCV2 non-structural protein antibody detection method that distinguishes between antibodies resulting from natural prior exposure (infection) and those induced by subunit vaccine immunization.Methodology. Based on the non-structural Rep' protein, we established an indirect ELISA (iELISA) using sera from guinea pigs and piglets.Results. The results for iELISA for guinea pig serum showed that animals vaccinated with a whole-virus inactivated PCV2 vaccine had 100 % (10/10) Cap antibody positivity and 100 % (10/10) Rep' antibody positivity. Guinea pigs vaccinated with a recombinant subunit PCV2 vaccine had 100 % (10/10) Cap antibody positivity, while no (0/10) guinea pigs were Rep' antibody-positive. The combined detection results for the Rep' iELISA and a PCV2 Antibody Test kit (Commercial) showed that pigs vaccinated with a whole-virus inactivated PCV2 vaccine or PCV2 SD/2017 had 100 % (5/5) Cap antibody positivity and 100 % (5/5) Rep' antibody positivity. Pigs vaccinated with a recombinant subunit PCV2 vaccine had 100 % (5/5) Cap antibody positivity, while no (0/10) pigs were Rep' antibody-positive.Conclusion. This paper describes an effective iELISA method that can distinguish natural infection with PCV2 (Cap and Rep positive) or inoculation with a whole-virus inactivated vaccine (Cap and Rep positive) from subunit vaccine immunization (Cap-positive, Rep-negative). These comparative assays could be very useful in the control of PCV2 in pig herds.


Assuntos
Anticorpos Antivirais/imunologia , Infecções por Circoviridae/sangue , Infecções por Circoviridae/veterinária , Circovirus/imunologia , Ensaio de Imunoadsorção Enzimática/métodos , Doenças dos Suínos/sangue , Proteínas Virais/imunologia , Vacinas Virais/imunologia , Animais , Anticorpos Antivirais/análise , Infecções por Circoviridae/imunologia , Circovirus/genética , Imunização , Suínos , Doenças dos Suínos/imunologia , Doenças dos Suínos/virologia , Vacinas de Subunidades/administração & dosagem , Vacinas de Subunidades/genética , Vacinas de Subunidades/imunologia , Proteínas Virais/administração & dosagem , Proteínas Virais/genética , Vacinas Virais/administração & dosagem , Vacinas Virais/genética
9.
PLoS One ; 15(8): e0237181, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32813697

RESUMO

Multidrug-resistant Vibrio parahaemolyticus has become a significant public health concern. The development of effective drugs and vaccines against Vibrio parahaemolyticus is the current research priority. Thus, we aimed to find out effective drug and vaccine targets using a comprehensive genome-based analysis. A total of 4822 proteins were screened from V. parahaemolyticus proteome. Among 16 novel cytoplasmic proteins, 'VIBPA Type II secretion system protein L' and 'VIBPA Putative fimbrial protein Z' were subjected to molecular docking with 350 human metabolites, which revealed that Eliglustat, Simvastatin and Hydroxocobalamin were the top drug molecules considering free binding energy. On the contrary, 'Sensor histidine protein kinase UhpB' and 'Flagellar hook-associated protein of 25 novel membrane proteins were subjected to T-cell and B-cell epitope prediction, antigenicity testing, transmembrane topology screening, allergenicity and toxicity assessment, population coverage analysis and molecular docking analysis to generate the most immunogenic epitopes. Three subunit vaccines were constructed by the combination of highly antigenic epitopes along with suitable adjuvant, PADRE sequence and linkers. The designed vaccine constructs (V1, V2, V3) were analyzed by their physiochemical properties and molecular docking with MHC molecules- results suggested that the V1 is superior. Besides, the binding affinity of human TLR-1/2 heterodimer and construct V1 could be biologically significant in the development of the vaccine repertoire. The vaccine-receptor complex exhibited deformability at a minimum level that also strengthened our prediction. The optimized codons of the designed construct was cloned into pET28a(+) vector of E. coli strain K12. However, the predicted drug molecules and vaccine constructs could be further studied using model animals to combat V. parahaemolyticus associated infections.


Assuntos
Vacinas Bacterianas/imunologia , Descoberta de Drogas/métodos , Genoma Bacteriano , Vibrioses/tratamento farmacológico , Vibrioses/prevenção & controle , Vibrio parahaemolyticus/genética , Vibrio parahaemolyticus/imunologia , Biologia Computacional/métodos , Farmacorresistência Bacteriana Múltipla/genética , Epitopos de Linfócito B/imunologia , Epitopos de Linfócito T/imunologia , Escherichia coli K12/genética , Humanos , Simulação de Acoplamento Molecular , Simulação de Dinâmica Molecular , Mapas de Interação de Proteínas , Proteoma/genética , Proteômica/métodos , Vacinas de Subunidades/imunologia , Vibrioses/microbiologia
10.
Sci Rep ; 10(1): 14179, 2020 08 25.
Artigo em Inglês | MEDLINE | ID: mdl-32843695

RESUMO

A novel coronavirus (SARS-CoV-2) emerged from China in late 2019 and rapidly spread across the globe, infecting millions of people and generating societal disruption on a level not seen since the 1918 influenza pandemic. A safe and effective vaccine is desperately needed to prevent the continued spread of SARS-CoV-2; yet, rational vaccine design efforts are currently hampered by the lack of knowledge regarding viral epitopes targeted during an immune response, and the need for more in-depth knowledge on betacoronavirus immunology. To that end, we developed a computational workflow using a series of open-source algorithms and webtools to analyze the proteome of SARS-CoV-2 and identify putative T cell and B cell epitopes. Utilizing a set of stringent selection criteria to filter peptide epitopes, we identified 41 T cell epitopes (5 HLA class I, 36 HLA class II) and 6 B cell epitopes that could serve as promising targets for peptide-based vaccine development against this emerging global pathogen. To our knowledge, this is the first study to comprehensively analyze all 10 (structural, non-structural and accessory) proteins from SARS-CoV-2 using predictive algorithms to identify potential targets for vaccine development.


Assuntos
Betacoronavirus/imunologia , Biologia Computacional , Infecções por Coronavirus/imunologia , Infecções por Coronavirus/virologia , Epitopos de Linfócito B/imunologia , Epitopos de Linfócito T/imunologia , Interações Hospedeiro-Patógeno/imunologia , Pneumonia Viral/imunologia , Pneumonia Viral/virologia , Proteínas Virais/imunologia , Sequência de Aminoácidos , Linfócitos B/imunologia , Linfócitos B/metabolismo , Betacoronavirus/classificação , Betacoronavirus/genética , Betacoronavirus/metabolismo , Biologia Computacional/métodos , Infecções por Coronavirus/metabolismo , Epitopos de Linfócito B/química , Epitopos de Linfócito T/química , Genoma Viral , Genômica/métodos , Humanos , Modelos Moleculares , Pandemias , Peptídeos/química , Peptídeos/imunologia , Filogenia , Pneumonia Viral/metabolismo , Relação Estrutura-Atividade , Linfócitos T/imunologia , Linfócitos T/metabolismo , Vacinas de Subunidades/imunologia , Proteínas Virais/química , Vacinas Virais/imunologia
12.
J Immunol Res ; 2020: 7201752, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32695833

RESUMO

The recent outbreak of the novel coronavirus disease, COVID-19, has highlighted the threat that highly pathogenic coronaviruses have on global health security and the imminent need to design an effective vaccine for prevention purposes. Although several attempts have been made to develop vaccines against human coronavirus infections since the emergence of Severe Acute Respiratory Syndrome coronavirus (SARS-CoV) in 2003, there is no available licensed vaccine yet. A better understanding of previous coronavirus vaccine studies may help to design a vaccine for the newly emerged virus, SARS-CoV-2, that may also cover other pathogenic coronaviruses as a potentially universal vaccine. In general, coronavirus spike protein is the major antigen for the vaccine design as it can induce neutralizing antibodies and protective immunity. By considering the high genetic similarity between SARS-CoV and SARS-CoV-2, here, protective immunity against SARS-CoV spike subunit vaccine candidates in animal models has been reviewed to gain advances that can facilitate coronavirus vaccine development in the near future.


Assuntos
Betacoronavirus/imunologia , Infecções por Coronavirus/prevenção & controle , Desenho de Fármacos , Pandemias/prevenção & controle , Pneumonia Viral/prevenção & controle , Glicoproteína da Espícula de Coronavírus/imunologia , Vacinas Virais , Animais , Anticorpos Neutralizantes , Anticorpos Antivirais , Betacoronavirus/genética , Infecções por Coronavirus/epidemiologia , Infecções por Coronavirus/imunologia , Infecções por Coronavirus/virologia , Avaliação Pré-Clínica de Medicamentos , Drogas em Investigação , Humanos , Pneumonia Viral/epidemiologia , Pneumonia Viral/imunologia , Pneumonia Viral/virologia , Vírus da SARS/genética , Vírus da SARS/imunologia , Síndrome Respiratória Aguda Grave/imunologia , Síndrome Respiratória Aguda Grave/prevenção & controle , Síndrome Respiratória Aguda Grave/virologia , Glicoproteína da Espícula de Coronavírus/genética , Vacinas de Subunidades/imunologia , Vacinas de Subunidades/uso terapêutico
13.
Int Immunopharmacol ; 86: 106738, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32683296

RESUMO

The beginning of 2020 was marked as the emergence of a COVID-19 outbreak caused by a new coronavirus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Currently, there is no vaccine or approved treatment for this infectious virus so the invention of an efficient vaccine is certainly a high priority. Some studies have employed several techniques to facilitate the combination of the immunoinformatics approach and comparative genomic approach in order to determine the potential peptides for designing the T-cell epitope-based peptide vaccine using the 2019-nCoV envelope protein as a target. Via screening the bioimmunoinformatic SARS-CoV2 derived B-cell and T-cell epitopes within the basic immunogenic of SARS-CoV2 proteins, we presented a set of inferred B-cell and T-cell epitopes from the spike (S) and nucleocapsid (N) proteins with high antigenicity and without allergenic property or toxic effects. Our findings provide a screened set of epitopes that can be introduced as potential targets for developing peptide vaccines against the SARS-CoV-2 virus.


Assuntos
Betacoronavirus/imunologia , Infecções por Coronavirus/prevenção & controle , Proteínas do Nucleocapsídeo/imunologia , Pandemias/prevenção & controle , Pneumonia Viral/prevenção & controle , Glicoproteína da Espícula de Coronavírus/imunologia , Vacinas Virais/imunologia , Biologia Computacional , Infecções por Coronavirus/epidemiologia , Infecções por Coronavirus/imunologia , Infecções por Coronavirus/virologia , Desenvolvimento de Medicamentos/métodos , Epitopos de Linfócito B/imunologia , Epitopos de Linfócito T/imunologia , Humanos , Pneumonia Viral/epidemiologia , Pneumonia Viral/imunologia , Pneumonia Viral/virologia , Vacinas de Subunidades/imunologia , Vacinas de Subunidades/uso terapêutico , Vacinas Virais/uso terapêutico
14.
Exp Parasitol ; 216: 107945, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32615133

RESUMO

Despite decades of investigation to clarify protective mechanisms of anticoccidial responses, one crucial field is neglected, that is, protective memory responses in primed birds. Protective memory immunity is critical for host resistance to reinfection and is the basis of modern vaccinology, especially in developing successful subunit vaccines. There are important differences between the immune responses induced by infections and antigens delivered either as killed, recombinant proteins or as live, replicating vector vaccines or as DNA vaccines. Animals immunized with these vaccines may fail to develop protective memory immunity, and is still naïve to Eimeria infection. This may explain why limited success is achieved in developing next-generation anticoccidial vaccines. In this review, we try to decipher the protective memory responses against Eimeria infection, assess immune responses elicited by various anticoccidial vaccine candidates, and propose possible approaches to develop rational vaccines that can induce a protective memory response to chicken coccidiosis.


Assuntos
Galinhas/parasitologia , Coccidiose/veterinária , Eimeria/imunologia , Memória Imunológica/fisiologia , Doenças das Aves Domésticas/imunologia , Vacinas Protozoárias , Animais , Galinhas/imunologia , Coccidiose/imunologia , Coccidiose/prevenção & controle , Intestinos/imunologia , Intestinos/parasitologia , Doenças das Aves Domésticas/prevenção & controle , Vacinas Protozoárias/imunologia , Recidiva , Vacinação/veterinária , Vacinas de Subunidades/imunologia
15.
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
16.
Cell Syst ; 11(2): 131-144.e6, 2020 08 26.
Artigo em Inglês | MEDLINE | ID: mdl-32721383

RESUMO

We present a combinatorial machine learning method to evaluate and optimize peptide vaccine formulations for SARS-CoV-2. Our approach optimizes the presentation likelihood of a diverse set of vaccine peptides conditioned on a target human-population HLA haplotype distribution and expected epitope drift. Our proposed SARS-CoV-2 MHC class I vaccine formulations provide 93.21% predicted population coverage with at least five vaccine peptide-HLA average hits per person (≥ 1 peptide: 99.91%) with all vaccine peptides perfectly conserved across 4,690 geographically sampled SARS-CoV-2 genomes. Our proposed MHC class II vaccine formulations provide 97.21% predicted coverage with at least five vaccine peptide-HLA average hits per person with all peptides having an observed mutation probability of ≤ 0.001. We provide an open-source implementation of our design methods (OptiVax), vaccine evaluation tool (EvalVax), as well as the data used in our design efforts here: https://github.com/gifford-lab/optivax.


Assuntos
Betacoronavirus/imunologia , Haplótipos , Antígenos de Histocompatibilidade Classe II/genética , Antígenos de Histocompatibilidade Classe I/genética , Análise de Sequência de DNA/métodos , Vacinas de Subunidades/imunologia , Vacinas Virais/imunologia , Betacoronavirus/genética , Infecções por Coronavirus/genética , Infecções por Coronavirus/imunologia , Infecções por Coronavirus/prevenção & controle , Epitopos/química , Epitopos/genética , Epitopos/imunologia , Antígenos de Histocompatibilidade Classe I/química , Antígenos de Histocompatibilidade Classe I/imunologia , Antígenos de Histocompatibilidade Classe II/química , Antígenos de Histocompatibilidade Classe II/imunologia , Humanos , Aprendizado de Máquina , Análise de Sequência de DNA/normas , Vacinas de Subunidades/química , Vacinas de Subunidades/genética , Vacinas Virais/química , Vacinas Virais/genética
17.
Mol Immunol ; 125: 123-130, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32659597

RESUMO

The development of a more efficient vaccine is needed to improve tuberculosis control. One of the current approaches is to identify immunogenic T-cell peptides that can elicit a protective and specific immune response. These peptides come from immunogenic proteins of the pathogen. The PE_PGRS33 protein of Mycobacterium tuberculosis has been proved immunogenic. However, little is known about immunogenic T-cell peptides of PE_PGRS33 and their interactions with MHC-II molecules. Therefore, we used the SYFPHEITHI database to determine the immunogenic PE_PGRS33 T-cell peptides. Next, we built homology models by using MOE v2018.1 software in order to obtain information about the specific interactions between the peptides and I-Ak. The AlgPred server was employed to look for allergenic sites in PE_PGRS33. We developed a sequence alignment between PE_PGRS33 and all the human proteins by using BLAST. Three peptides were commercially synthesized, and their activity was evaluated in vitro by the stimulation of PBMC from household contacts of TB patients. Our in silico results showed five immunogenic T-cell peptides. BLAST analysis showed low homology of PE_PGRS33 with human proteins and AlgPred did not reveal allergenic sites in PE_PGRS33. The three peptides triggered the activation of CD4+ T cells from the households contacts, showed by the production of IFN-γ. We identified three immunogenic peptides of PE_PGRS33 that demonstrated activity in vitro which allows to deepen into the immune response towards mycobacterial antigens, moving forward to the identification of new vaccine candidates.


Assuntos
Antígenos de Bactérias/imunologia , Linfócitos T CD4-Positivos/imunologia , Mycobacterium tuberculosis/imunologia , Vacinas contra a Tuberculose/imunologia , Humanos , Ativação Linfocitária/imunologia , Peptídeos/imunologia , Vacinas de Subunidades/imunologia
18.
Vaccine ; 38(32): 5071-5075, 2020 07 06.
Artigo em Inglês | MEDLINE | ID: mdl-32513514

RESUMO

SARS-CoV-2 is the cause of the worldwide outbreak of COVID-19 that has been characterized as a pandemic by the WHO. Since the first report of COVID-19 on December 31, 2019, 179,111 cases were confirmed in 160 countries/regions with 7426 deaths as of March 17, 2020. However, there have been no vaccines approved in the world to date. In this study, we analyzed the biological characteristics of the SARS-CoV-2 Spike protein, Pro330-Leu650 (SARS-CoV-2-SPL), using biostatistical methods. SARS-CoV-2-SPL possesses a receptor-binding region (RBD) and important B (Ser438-Gln506, Thr553-Glu583, Gly404-Aps427, Thr345-Ala352, and Lys529-Lys535) and T (9 CD4 and 11 CD8 T cell antigenic determinants) cell epitopes. High homology in this region between SARS-CoV-2 and SARS-CoV amounted to 87.7%, after taking the biological similarity of the amino acids into account and eliminating the receptor-binding motif (RBM). The overall topology indicated that the complete structure of SARS-CoV-2-SPL was with RBM as the head, and RBD as the trunk and the tail region. SARS-CoV-2-SPL was found to have the potential to elicit effective B and T cell responses. Our findings may provide meaningful guidance for SARS-CoV-2 vaccine design.


Assuntos
Betacoronavirus/química , Desenho de Fármacos , Modelos Imunológicos , Glicoproteína da Espícula de Coronavírus/química , Glicoproteína da Espícula de Coronavírus/imunologia , Vacinas Virais/química , Vacinas Virais/imunologia , Sequência de Aminoácidos , Antígenos Virais/química , Antígenos Virais/imunologia , Betacoronavirus/imunologia , Infecções por Coronavirus/epidemiologia , Infecções por Coronavirus/imunologia , Infecções por Coronavirus/prevenção & controle , Infecções por Coronavirus/virologia , Epitopos de Linfócito B/química , Epitopos de Linfócito B/imunologia , Epitopos de Linfócito T/química , Epitopos de Linfócito T/imunologia , Humanos , Modelos Moleculares , Pandemias/prevenção & controle , Pneumonia Viral/epidemiologia , Pneumonia Viral/imunologia , Pneumonia Viral/prevenção & controle , Pneumonia Viral/virologia , Alinhamento de Sequência , Vacinas de Subunidades/química , Vacinas de Subunidades/imunologia
19.
Biomed Res Int ; 2020: 2683286, 2020.
Artigo em Inglês | MEDLINE | ID: covidwho-400795

RESUMO

Background: A new endemic disease has spread across Wuhan City, China, in December 2019. Within few weeks, the World Health Organization (WHO) announced a novel coronavirus designated as coronavirus disease 2019 (COVID-19). In late January 2020, WHO declared the outbreak of a "public-health emergency of international concern" due to the rapid and increasing spread of the disease worldwide. Currently, there is no vaccine or approved treatment for this emerging infection; thus, the objective of this study is to design a multiepitope peptide vaccine against COVID-19 using an immunoinformatics approach. Method: Several techniques facilitating the combination of the immunoinformatics approach and comparative genomic approach were used in order to determine the potential peptides for designing the T-cell epitope-based peptide vaccine using the envelope protein of 2019-nCoV as a target. Results: Extensive mutations, insertion, and deletion were discovered with comparative sequencing in the COVID-19 strain. Additionally, ten peptides binding to MHC class I and MHC class II were found to be promising candidates for vaccine design with adequate world population coverage of 88.5% and 99.99%, respectively. Conclusion: The T-cell epitope-based peptide vaccine was designed for COVID-19 using the envelope protein as an immunogenic target. Nevertheless, the proposed vaccine rapidly needs to be validated clinically in order to ensure its safety and immunogenic profile to help stop this epidemic before it leads to devastating global outbreaks.


Assuntos
Betacoronavirus/imunologia , Biologia Computacional/métodos , Infecções por Coronavirus/imunologia , Epitopos/imunologia , Pneumonia Viral/imunologia , Vacinas de Subunidades/imunologia , Proteínas Virais/imunologia , Vacinas Virais/imunologia , Sequência de Aminoácidos , Infecções por Coronavirus/prevenção & controle , Epitopos/química , Epitopos de Linfócito T/imunologia , Evolução Molecular , Antígenos HLA/imunologia , Humanos , Modelos Moleculares , Pandemias , Software , Proteínas Virais/química
20.
Vaccine ; 38(28): 4464-4475, 2020 06 09.
Artigo em Inglês | MEDLINE | ID: covidwho-133338

RESUMO

The 2013-2016 West Africa EBOV epidemic was the biggest EBOV outbreak to date. An analysis of virus-specific CD8+ T-cell immunity in 30 survivors showed that 26 of those individuals had a CD8+ response to at least one EBOV protein. The dominant response (25/26 subjects) was specific to the EBOV nucleocapsid protein (NP). It has been suggested that epitopes on the EBOV NP could form an important part of an effective T-cell vaccine for Ebola Zaire. We show that a 9-amino-acid peptide NP44-52 (YQVNNLEEI) located in a conserved region of EBOV NP provides protection against morbidity and mortality after mouse adapted EBOV challenge. A single vaccination in a C57BL/6 mouse using an adjuvanted microsphere peptide vaccine formulation containing NP44-52 is enough to confer immunity in mice. Our work suggests that a peptide vaccine based on CD8+ T-cell immunity in EBOV survivors is conceptually sound and feasible. Nucleocapsid proteins within SARS-CoV-2 contain multiple Class I epitopes with predicted HLA restrictions consistent with broad population coverage. A similar approach to a CTL vaccine design may be possible for that virus.


Assuntos
Desenho de Fármacos , Vacinas contra Ebola/imunologia , Epitopos de Linfócito T/imunologia , Proteínas do Nucleocapsídeo/imunologia , Linfócitos T Citotóxicos/imunologia , Vacinas de Subunidades/imunologia , Vacinas Virais , Sequência de Aminoácidos , Animais , Infecções por Coronavirus/imunologia , Infecções por Coronavirus/prevenção & controle , Modelos Animais de Doenças , Vacinas contra Ebola/química , Epitopos de Linfócito T/química , Doença pelo Vírus Ebola/imunologia , Doença pelo Vírus Ebola/prevenção & controle , Humanos , Camundongos , Camundongos Endogâmicos C57BL , Proteínas do Nucleocapsídeo/química , Pandemias/prevenção & controle , Pneumonia Viral/imunologia , Pneumonia Viral/prevenção & controle , Vacinas de Subunidades/química , Vacinas Virais/química , Vacinas Virais/imunologia
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