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1.
J Gen Virol ; 102(8)2021 08.
Artigo em Inglês | MEDLINE | ID: mdl-34435944

RESUMO

Human pathogens belonging to the Alphavirus genus, in the Togaviridae family, are transmitted primarily by mosquitoes. The signs and symptoms associated with these viruses include fever and polyarthralgia, defined as joint pain and inflammation, as well as encephalitis. In the last decade, our understanding of the interactions between members of the alphavirus genus and the human host has increased due to the re-appearance of the chikungunya virus (CHIKV) in Asia and Europe, as well as its emergence in the Americas. Alphaviruses affect host immunity through cytokines and the interferon response. Understanding alphavirus interactions with both the innate immune system as well as the various cells in the adaptive immune systems is critical to developing effective therapeutics. In this review, we summarize the latest research on alphavirus-host cell interactions, underlying infection mechanisms, and possible treatments.


Assuntos
Infecções por Alphavirus , Alphavirus , Alphavirus/imunologia , Alphavirus/patogenicidade , Infecções por Alphavirus/epidemiologia , Infecções por Alphavirus/prevenção & controle , Infecções por Alphavirus/virologia , Animais , Humanos , Vacinas Virais/imunologia
2.
Int J Mol Sci ; 22(16)2021 Aug 16.
Artigo em Inglês | MEDLINE | ID: mdl-34445493

RESUMO

Classical swine fever (CSF) is a highly contagious disease caused by the classical swine fever virus (CSFV). The live attenuated C-strain vaccine is highly efficacious, initiating protection within several days of delivery. The vaccine strain is detected in the tonsil early after inoculation, yet little is known of the role that tonsillar immune cells might play in initiating protection. Comparing the C-strain vaccine with the pathogenic CSFV Alfort-187 strain, changes in the myeloid cell compartment of the tonsil were observed. CSFV infection led to the emergence of an additional CD163+CD14+ cell population, which showed the highest levels of Alfort-187 and C-strain infection. There was also an increase in both the frequency and activation status (as shown by increased MHC-II expression) of the tonsillar conventional dendritic cells 1 (cDC1) in pigs inoculated with the C-strain. Notably, the activation of cDC1 cells coincided in time with the induction of a local CSFV-specific IFN-γ+ CD8 T cell response in C-strain vaccinated pigs, but not in pigs that received Alfort-187. Moreover, the frequency of CSFV-specific IFN-γ+ CD8 T cells was inversely correlated to the viral load in the tonsils of individual animals. Accordingly, we hypothesise that the activation of cDC1 is key in initiating local CSFV-specific CD8 T cell responses which curtail early virus replication and dissemination.


Assuntos
Linfócitos T CD8-Positivos/metabolismo , Vírus da Febre Suína Clássica/imunologia , Peste Suína Clássica/prevenção & controle , Tonsila Palatina/imunologia , Vacinas Virais/administração & dosagem , Animais , Antígenos CD/metabolismo , Antígenos de Diferenciação Mielomonocítica/metabolismo , Peste Suína Clássica/imunologia , Peste Suína Clássica/virologia , Vírus da Febre Suína Clássica/fisiologia , Células Dendríticas/metabolismo , Interferon gama/metabolismo , Receptores de Lipopolissacarídeos/metabolismo , Células Mieloides/metabolismo , Tonsila Palatina/citologia , Tonsila Palatina/virologia , Receptores de Superfície Celular/metabolismo , Suínos , Vacinas Atenuadas/administração & dosagem , Vacinas Atenuadas/imunologia , Carga Viral , Vacinas Virais/imunologia
3.
BMC Infect Dis ; 21(1): 650, 2021 Jul 05.
Artigo em Inglês | MEDLINE | ID: mdl-34225650

RESUMO

BACKGROUND: Hand, foot, and mouth disease (HFMD) is a common illness in young children. A monovalent vaccine has been developed in China protecting against enterovirus-71, bivalent vaccines preventing HFMD caused by two viruses are under development. OBJECTIVE: To predict and compare the incidence of HFMD under different vaccination scenarios in China. METHODS: We developed a compartmental model to capture enterovirus transmission and the natural history of HFMD in children aged 0-5, and calibrated to reported cases in the same age-group from 2015 to 2018. We compared the following vaccination scenarios: different combinations of monovalent and bivalent vaccine; a program of constant vaccination to that of pulse vaccination prior to seasonal outbreaks. RESULTS: We estimate 1,982,819, 2,258,846, 1,948,522 and 2,398,566 cases from 2015 to 2018. Increased coverage of monovalent vaccine from 0 to 80% is predicted to decrease the cases by 797,262 (49.1%). Use of bivalent vaccine at an 80% coverage level would decrease the cases by 828,560. Use of a 2.0× pulse vaccination for the bivalent vaccine in addition to 80% coverage would reduce cases by over one million. The estimated R0 for HFMD in 2015-2018 was 1.08, 1.10, 1.35 and 1.17. CONCLUSIONS: Our results point to the benefit of bivalent vaccine and using a pulse vaccination in specific months over routine vaccination. Other ways to control HFMD include isolation of patients in the early stage of dissemination, more frequent hand-washing and ventilation, and better treatment options for patients.


Assuntos
Enterovirus/imunologia , Doença de Mão, Pé e Boca/prevenção & controle , Vacinação , Vacinas Virais/imunologia , Pré-Escolar , China/epidemiologia , Feminino , Doença de Mão, Pé e Boca/epidemiologia , Humanos , Lactente , Recém-Nascido , Masculino , Modelos Teóricos , Vacinas Combinadas/imunologia
4.
Science ; 373(6558): 991-998, 2021 08 27.
Artigo em Inglês | MEDLINE | ID: mdl-34214046

RESUMO

The emergence of severe acute respiratory syndrome coronavirus (SARS-CoV) in 2003 and SARS-CoV-2 in 2019 highlights the need to develop universal vaccination strategies against the broader Sarbecovirus subgenus. Using chimeric spike designs, we demonstrate protection against challenge from SARS-CoV, SARS-CoV-2, SARS-CoV-2 B.1.351, bat CoV (Bt-CoV) RsSHC014, and a heterologous Bt-CoV WIV-1 in vulnerable aged mice. Chimeric spike messenger RNAs (mRNAs) induced high levels of broadly protective neutralizing antibodies against high-risk Sarbecoviruses. By contrast, SARS-CoV-2 mRNA vaccination not only showed a marked reduction in neutralizing titers against heterologous Sarbecoviruses, but SARS-CoV and WIV-1 challenge in mice resulted in breakthrough infections. Chimeric spike mRNA vaccines efficiently neutralized D614G, mink cluster five, and the UK B.1.1.7 and South African B.1.351 variants of concern. Thus, multiplexed-chimeric spikes can prevent SARS-like zoonotic coronavirus infections with pandemic potential.


Assuntos
Betacoronavirus/imunologia , Vacinas contra COVID-19/imunologia , Infecções por Coronavirus/prevenção & controle , Glicoproteína da Espícula de Coronavírus/imunologia , Vacinas Sintéticas/imunologia , Vacinas Virais/imunologia , Animais , Anticorpos Neutralizantes/imunologia , Anticorpos Antivirais/imunologia , Betacoronavirus/fisiologia , COVID-19/prevenção & controle , Infecções por Coronavirus/imunologia , Proteção Cruzada , Citocinas/sangue , Feminino , Imunidade Heteróloga , Imunogenicidade da Vacina , Lipossomos , Pulmão/patologia , Pulmão/virologia , Camundongos , Camundongos Endogâmicos BALB C , Nanopartículas , Domínios Proteicos , Proteínas Recombinantes de Fusão , Vírus da SARS/imunologia , Vírus da SARS/fisiologia , SARS-CoV-2/imunologia , SARS-CoV-2/fisiologia , Síndrome Respiratória Aguda Grave/prevenção & controle , Glicoproteína da Espícula de Coronavírus/química , Glicoproteína da Espícula de Coronavírus/genética , Replicação Viral
5.
Arch Virol ; 166(10): 2733-2741, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34322722

RESUMO

Congenital tremor (CT) type A-II in piglets is a worldwide disease caused by an emerging atypical porcine pestivirus (APPV). Preparation and evaluation of vaccines in laboratory animals is an important preliminary step toward prevention and control of the disease. Here, virus-like particles (VLPs) of APPV were prepared and VLPs vaccine was evaluated in BALB/c mice. Purified Erns and E2 proteins expressed in E. coli were allowed to self-assemble into VLPs, which had the appearance of hollow spherical particles with a diameter of about 100 nm by transmission electron microscopy (TEM). The VLPs induced strong antibody responses and reduced the viral load in tissues of BALB/c mice. The data from animal challenge experiments, RT-PCR, and immunohistochemical analysis demonstrated that BALB/c mice are an appropriate laboratory model for APPV. These results suggest the feasibility of using VLPs as a vaccine for the prevention and control of APPV and provide useful information for further study of APPV in laboratory animals.


Assuntos
Infecções por Pestivirus/prevenção & controle , Pestivirus/imunologia , Vacinação/veterinária , Replicação Viral/efeitos dos fármacos , Animais , Anticorpos Antivirais/sangue , Modelos Animais de Doenças , Camundongos , Camundongos Endogâmicos BALB C , Infecções por Pestivirus/virologia , Proteínas Recombinantes/genética , Proteínas Recombinantes/imunologia , Suínos , Doenças dos Suínos/prevenção & controle , Doenças dos Suínos/virologia , Vacinas de Partículas Semelhantes a Vírus/genética , Vacinas de Partículas Semelhantes a Vírus/imunologia , Proteínas do Envelope Viral/genética , Proteínas do Envelope Viral/imunologia , Carga Viral , Vacinas Virais/genética , Vacinas Virais/imunologia
6.
Int J Mol Sci ; 22(13)2021 Jun 28.
Artigo em Inglês | MEDLINE | ID: mdl-34203268

RESUMO

Viral-associated respiratory infectious diseases are one of the most prominent subsets of respiratory failures, known as viral respiratory infections (VRI). VRIs are proceeded by an infection caused by viruses infecting the respiratory system. For the past 100 years, viral associated respiratory epidemics have been the most common cause of infectious disease worldwide. Due to several drawbacks of the current anti-viral treatments, such as drug resistance generation and non-targeting of viral proteins, the development of novel nanotherapeutic or nano-vaccine strategies can be considered essential. Due to their specific physical and biological properties, nanoparticles hold promising opportunities for both anti-viral treatments and vaccines against viral infections. Besides the specific physiological properties of the respiratory system, there is a significant demand for utilizing nano-designs in the production of vaccines or antiviral agents for airway-localized administration. SARS-CoV-2, as an immediate example of respiratory viruses, is an enveloped, positive-sense, single-stranded RNA virus belonging to the coronaviridae family. COVID-19 can lead to acute respiratory distress syndrome, similarly to other members of the coronaviridae. Hence, reviewing the current and past emerging nanotechnology-based medications on similar respiratory viral diseases can identify pathways towards generating novel SARS-CoV-2 nanotherapeutics and/or nano-vaccines.


Assuntos
Antivirais/química , Portadores de Fármacos/química , Nanomedicina , Infecções Respiratórias/patologia , Vacinas Virais/química , Viroses/patologia , Antivirais/uso terapêutico , COVID-19/imunologia , COVID-19/patologia , COVID-19/terapia , COVID-19/virologia , Humanos , Sistema Imunitário/metabolismo , Infecções Respiratórias/terapia , Infecções Respiratórias/virologia , SARS-CoV-2/isolamento & purificação , Vacinas Virais/administração & dosagem , Vacinas Virais/imunologia , Viroses/imunologia , Viroses/prevenção & controle , Viroses/terapia
7.
Microb Pathog ; 158: 105091, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34274453

RESUMO

Newcastle disease virus (NDV) is one of the most important diseases in poultry. The present study generated recombinant surface-displayed Lactobacillus casei (L. casei) expressing the hemagglutinin-neuraminidase (HN) of NDV (Lc-pPG-HN) and a live pPG vector (Lc-pPG) and evaluated their immunogenicity. A 1670 bp HN gene fragment was successfully amplified and cloned into a prokaryotic protein expression system. Protein expression in the resulting recombinant Lc-pPG-HN (surface displayed) strain was verified using Western blotting and indirect immunofluorescence. A single band was observed on the Western blots, and the molecular weight of the corresponding protein was 63 kDa. A fluorescent signal for Lc-pPG-HN was observed using fluorescence microscopy. A total of 270 healthy chicks were divided into three treatment groups. Five replicates were used for each treatment, while six chicks were used per replicate. The following three treatment groups were used: physiological saline group (Control), Lc-pPG group and recombinant vaccine group (Lc-pPG-HN). The primary immunization and booster immunization of the chicks were performed via oral administration on 1 and 10 days old. Tissue and blood samples were collected from chickens that received oral recombinant L. casei strains on 1, 7, 14 and 21 days post-immunization for immune-related index analyses. Chickens orally immunized with Lc-pPG-HN showed significantly increased body weights and immune organ indices. Oral immunization with Lc-pPG-HN also enhanced the concentrations of serum interleukin-2 (IL-2), interferon-γ (IFN-γ), intestinal lavage fluid secretory immunoglobulin A (SIgA) and histomorphological development of the small intestine. Our results also indicated that recombinant L. casei significantly increased Lactobacillus and Bifidobacterium colonization and decreased the relative abundance of Escherichia coli (E. coli) in the chicken caecum. Similar enhancement effects from hemagglutination inhibition were also observed in the antibody titers. Oral administration of Lc-pPG-HN effectively protected against NDV and alleviated the symptoms of the NDV challenge. In summary, recombinant L. casei had positive impacts on the performance, immunological function, gut development, and microbiota of growing chicks and may be a potential therapeutic candidate against NDV.


Assuntos
Lactobacillus casei , Doença de Newcastle , Vacinas Virais , Animais , Anticorpos Antivirais , Galinhas/imunologia , Escherichia coli , Hemaglutininas/imunologia , Imunidade , Lactobacillus casei/genética , Neuraminidase/imunologia , Doença de Newcastle/prevenção & controle , Vírus da Doença de Newcastle/genética , Vacinas Virais/genética , Vacinas Virais/imunologia
8.
Sci Rep ; 11(1): 15431, 2021 07 29.
Artigo em Inglês | MEDLINE | ID: mdl-34326355

RESUMO

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


Assuntos
Epitopos/imunologia , Coronavírus da Síndrome Respiratória do Oriente Médio/imunologia , Vacinas/imunologia , Biologia Computacional , Infecções por Coronavirus/imunologia , Infecções por Coronavirus/prevenção & controle , Epitopos de Linfócito B/genética , Epitopos de Linfócito B/imunologia , Epitopos de Linfócito T/genética , Epitopos de Linfócito T/imunologia , Humanos , Imunogenicidade da Vacina/imunologia , Coronavírus da Síndrome Respiratória do Oriente Médio/genética , Coronavírus da Síndrome Respiratória do Oriente Médio/patogenicidade , Modelos Moleculares , Simulação de Acoplamento Molecular , Filogenia , Ligação Proteica , Glicoproteína da Espícula de Coronavírus/imunologia , Linfócitos T Citotóxicos/imunologia , Linfócitos T Auxiliares-Indutores/imunologia , Vacinas/farmacologia , Vacinas de Subunidades/imunologia , Vacinas Virais/imunologia
9.
Viruses ; 13(7)2021 06 23.
Artigo em Inglês | MEDLINE | ID: mdl-34201591

RESUMO

A 59-year-old male with follicular lymphoma treated by anti-CD20-mediated B-cell depletion and ablative chemotherapy was hospitalized with a COVID-19 infection. Although the patient did not develop specific humoral immunity, he had a mild clinical course overall. The failure of all therapeutic options allowed infection to persist nearly 300 days with active accumulation of SARS-CoV-2 virus mutations. As a rescue therapy, an infusion of REGEN-COV (10933 and 10987) anti-spike monoclonal antibodies was performed 270 days from initial diagnosis. Due to partial clearance after the first dose (2.4 g), a consolidation dose (8 g) was infused six weeks later. Complete virus clearance could then be observed over the following month, after he was vaccinated with the Pfizer-BioNTech anti-COVID-19 vaccination. The successful management of this patient required prolonged enhanced quarantine, monitoring of virus mutations, pioneering clinical decisions based upon close consultation, and the coordination of multidisciplinary experts in virology, immunology, pharmacology, input from REGN, the FDA, the IRB, the health care team, the patient, and the patient's family. Current decisions to take revolve around patient's follicular lymphoma management, and monitoring for virus clearance persistence beyond disappearance of REGEN-COV monoclonal antibodies after anti-SARS-CoV-2 vaccination. Overall, specific guidelines for similar cases should be established.


Assuntos
Anticorpos Monoclonais/uso terapêutico , Linfócitos B/imunologia , COVID-19/imunologia , COVID-19/terapia , SARS-CoV-2/imunologia , Glicoproteína da Espícula de Coronavírus/imunologia , COVID-19/complicações , Humanos , Imunidade Humoral , Depleção Linfocítica , Linfoma Folicular/tratamento farmacológico , Linfoma Folicular/terapia , Masculino , Pessoa de Meia-Idade , SARS-CoV-2/genética , Vacinas Virais/administração & dosagem , Vacinas Virais/imunologia
10.
Viruses ; 13(7)2021 06 23.
Artigo em Inglês | MEDLINE | ID: mdl-34201767

RESUMO

We summarize here in vitro evidences of efficacy for convalescent plasma, currently approved vaccines and monoclonal antibodies against SARS-CoV-2 variants of concern (VOC: B.1.1.7, B.1.351, P.1, and B.1.617.2), variants of interest (VOI: B.1.427/B.1.429, P.2, B.1.525, P.3, B.1.526, and B.1.671.1), and other strains (B.1.1.298 and B.1.258delta). While waiting from real world clinical efficacy, these data provide guidance for the treating physician.


Assuntos
Anticorpos Monoclonais/imunologia , Anticorpos Antivirais/sangue , Plasma/imunologia , SARS-CoV-2/imunologia , Vacinas Virais/imunologia , Anticorpos Monoclonais Humanizados/imunologia , Anticorpos Neutralizantes/imunologia , COVID-19/terapia , Humanos , Imunização Passiva/normas , Técnicas In Vitro , Testes de Neutralização , Glicoproteína da Espícula de Coronavírus/imunologia
11.
Viruses ; 13(7)2021 06 24.
Artigo em Inglês | MEDLINE | ID: mdl-34202573

RESUMO

Adenovirus vector-based genetic vaccines have emerged as a powerful strategy against the SARS-CoV-2 health crisis. This success is not unexpected because adenoviruses combine many desirable features of a genetic vaccine. They are highly immunogenic and have a low and well characterized pathogenic profile paired with technological approachability. Ongoing efforts to improve adenovirus-vaccine vectors include the use of rare serotypes and non-human adenoviruses. In this review, we focus on the viral capsid and how the choice of genotypes influences the uptake and subsequent subcellular sorting. We describe how understanding capsid properties, such as stability during the entry process, can change the fate of the entering particles and how this translates into differences in immunity outcomes. We discuss in detail how mutating the membrane lytic capsid protein VI affects species C viruses' post-entry sorting and briefly discuss if such approaches could have a wider implication in vaccine and/or vector development.


Assuntos
Adenovírus Humanos/imunologia , Adenovírus Humanos/fisiologia , Capsídeo/metabolismo , Vetores Genéticos , Vacinas Virais/imunologia , Internalização do Vírus , Imunidade Adaptativa , Adenovírus Humanos/genética , Animais , Anticorpos Neutralizantes/imunologia , Anticorpos Antivirais/imunologia , COVID-19/imunologia , Capsídeo/imunologia , Proteínas do Capsídeo/genética , Proteínas do Capsídeo/imunologia , Proteínas do Capsídeo/metabolismo , Ensaios Clínicos como Assunto , Humanos , Imunidade Inata , Camundongos , SARS-CoV-2/imunologia
12.
Gene ; 801: 145831, 2021 Oct 30.
Artigo em Inglês | MEDLINE | ID: mdl-34274485

RESUMO

The main strategy for preventing porcine reproductive and respiratory syndrome (PRRS) is vaccination. However, current commercial porcine reproductive and respiratory syndrome virus (PRRSV) vaccines have limited effectiveness and may even cause infections in pigs. The identification of stable molecular markers associated with immune responses to PRRSV vaccination in pigs provides a new approach for PRRS prevention. DNA methylation, the most stable epigenetic molecular marker related to PRRSV vaccination, has not been investigated. In the current research, we used whole genome bisulfite sequencing (WGBS) to investigate DNA methylation in pregnant sows that received PRRSV vaccination and their piglets with high and low PRRSV-specific antibody levels. By performing methylation data analysis and basing on our previous transcriptomic studies, we identified several differentially methylated genes (DMGs) that are involved in the pathways of inflammatory and immune responses. Among the DMGs, ISG15, MX1, SERPINE1, GNG11 and IFIT3 were common hub genes in the two generations. MX1 and GNG11 were located in quantitative trait loci related with PRRSV antibody titer and PRRSV susceptibility, respectively. These results suggest that PRRSV vaccination in sows induces DNA methylation changes in genes and DNA methylation changes occur through intergenerational transmission. The novel DNA methylation markers and target genes observed in our study provide new insights into the molecular mechanisms of immune responses to PRRSV vaccination across two pig generations.


Assuntos
Anticorpos Antivirais/sangue , Metilação de DNA , Síndrome Respiratória e Reprodutiva Suína/genética , Vacinas Virais/imunologia , Animais , Animais Recém-Nascidos/imunologia , Animais Recém-Nascidos/virologia , Anticorpos Antivirais/genética , Feminino , Regulação da Expressão Gênica , Ontologia Genética , Transmissão Vertical de Doenças Infecciosas , Síndrome Respiratória e Reprodutiva Suína/imunologia , Síndrome Respiratória e Reprodutiva Suína/transmissão , Gravidez , Prenhez , Mapas de Interação de Proteínas/genética , Mapas de Interação de Proteínas/imunologia , Locos de Características Quantitativas , Suínos
13.
Nat Commun ; 12(1): 4636, 2021 07 30.
Artigo em Inglês | MEDLINE | ID: mdl-34330906

RESUMO

Chikungunya virus (CHIKV) is a reemerging mosquito-borne virus that causes swift outbreaks. Major concerns are the persistent and disabling polyarthralgia in infected individuals. Here we present the results from a first-in-human trial of the candidate simian adenovirus vectored vaccine ChAdOx1 Chik, expressing the CHIKV full-length structural polyprotein (Capsid, E3, E2, 6k and E1). 24 adult healthy volunteers aged 18-50 years, were recruited in a dose escalation, open-label, nonrandomized and uncontrolled phase 1 trial (registry NCT03590392). Participants received a single intramuscular injection of ChAdOx1 Chik at one of the three preestablished dosages and were followed-up for 6 months. The primary objective was to assess safety and tolerability of ChAdOx1 Chik. The secondary objective was to assess the humoral and cellular immunogenicity. ChAdOx1 Chik was safe at all doses tested with no serious adverse reactions reported. The vast majority of solicited adverse events were mild or moderate, and self-limiting in nature. A single dose induced IgG and T-cell responses against the CHIKV structural antigens. Broadly neutralizing antibodies against the four CHIKV lineages were found in all participants and as early as 2 weeks after vaccination. In summary, ChAdOx1 Chik showed excellent safety, tolerability and 100% PRNT50 seroconversion after a single dose.


Assuntos
Anticorpos Neutralizantes/imunologia , Anticorpos Antivirais/imunologia , Febre de Chikungunya/imunologia , Vírus Chikungunya/imunologia , Vacinas Virais/imunologia , Adolescente , Adulto , Febre de Chikungunya/prevenção & controle , Febre de Chikungunya/virologia , Vírus Chikungunya/classificação , Vírus Chikungunya/fisiologia , Citocinas/imunologia , Citocinas/metabolismo , Ensaio de Imunoadsorção Enzimática , Fadiga/induzido quimicamente , Feminino , Cefaleia/induzido quimicamente , Humanos , Imunoglobulina G/imunologia , Injeções Intramusculares , Masculino , Pessoa de Meia-Idade , Linfócitos T/imunologia , Linfócitos T/metabolismo , Vacinação/métodos , Vacinas Virais/administração & dosagem , Vacinas Virais/efeitos adversos , Adulto Jovem
14.
Cell Rep ; 36(4): 109452, 2021 07 27.
Artigo em Inglês | MEDLINE | ID: mdl-34289385

RESUMO

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


Assuntos
Anticorpos Neutralizantes/farmacologia , SARS-CoV-2/patogenicidade , Glicoproteína da Espícula de Coronavírus/imunologia , Vacinas Virais/farmacologia , Administração Intranasal/métodos , Animais , Anticorpos Neutralizantes/imunologia , Anticorpos Antivirais/imunologia , Anticorpos Antivirais/farmacologia , Camundongos , Vacinação/métodos , Vacinas Virais/imunologia
16.
Adv Sci (Weinh) ; 8(16): e2100985, 2021 08.
Artigo em Inglês | MEDLINE | ID: mdl-34176237

RESUMO

COVID-19 is disastrous to global health and the economy. SARS-CoV-2 infection exhibits similar clinical symptoms and immunopathological sequelae to SARS-CoV infection. Therefore, much of the developmental progress on SARS-CoV vaccines can be utilized for the development of SARS-CoV-2 vaccines. Careful antigen selection during development is always of utmost importance for the production of effective vaccines that do not compromise recipient safety. This holds especially true for SARS-CoV vaccines, as several immunopathological disorders are associated with the activity of structural and nonstructural proteins encoded in the virus's genetic material. Whole viral protein and RNA-encoding full-length proteins contain both protective and "dangerous" sequences, unless pathological fragments are deleted. In light of recent advances, peptide vaccines may present a very safe and effective alternative. Peptide vaccines can avoid immunopathological pro-inflammatory sequences, focus immune responses on neutralizing immunogenic epitopes, avoid off-target antigen loss, combine antigens with different protective roles or mechanisms, even from different viral proteins, and avoid mutant escape by employing highly conserved cryptic epitopes. In this review, an attempt is made to exploit the similarities between SARS-CoV and SARS-CoV-2 in vaccine antigen screening, with particular attention to the pathological and immunogenic properties of SARS proteins.


Assuntos
Anticorpos Neutralizantes/imunologia , Anticorpos Antivirais/imunologia , COVID-19/prevenção & controle , SARS-CoV-2/imunologia , Vacinas Virais/imunologia , COVID-19/imunologia , COVID-19/patologia , COVID-19/virologia , Humanos , Glicoproteína da Espícula de Coronavírus/imunologia , Vacinas de Subunidades/administração & dosagem , Vacinas de Subunidades/imunologia , Vacinas Virais/administração & dosagem
17.
Int Immunopharmacol ; 96: 107763, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-34162141

RESUMO

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the causative agent of the rapidly spreading pandemic COVID-19 in the world. As an effective therapeutic strategy is not introduced yet and the rapid genetic variations in the virus, there is an emerging necessity to design, evaluate and apply effective new vaccines. An acceptable vaccine must elicit both humoral and cellular immune responses, must have the least side effects and the storage and transport systems should be available and affordable for all countries. These vaccines can be classified into different types: inactivated vaccines, live-attenuated virus vaccines, subunit vaccines, virus-like particles (VLPs), nucleic acid-based vaccines (DNA and RNA) and recombinant vector-based vaccines (replicating and non-replicating viral vector). According to the latest update of the WHO report on April 2nd, 2021, at least 85 vaccine candidates were being studied in clinical trial phases and 184 candidate vaccines were being evaluated in pre-clinical stages. In addition, studies have shown that other vaccines, including the Bacillus Calmette-Guérin (BCG) vaccine and the Plant-derived vaccine, may play a role in controlling pandemic COVID-19. Herein, we reviewed the different types of COVID-19 candidate vaccines that are currently being evaluated in preclinical and clinical trial phases along with advantages, disadvantages or adverse reactions, if any.


Assuntos
Vacinas contra COVID-19/imunologia , COVID-19/imunologia , COVID-19/prevenção & controle , SARS-CoV-2/imunologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Animais , Vacina BCG/imunologia , Vacinas contra COVID-19/administração & dosagem , Vacinas contra COVID-19/efeitos adversos , Avaliação Pré-Clínica de Medicamentos , Feminino , Humanos , Masculino , Metanálise como Assunto , Pessoa de Meia-Idade , Vacinas de DNA/imunologia , Vacinas de Produtos Inativados/imunologia , Vacinas de Subunidades/imunologia , Vacinas de Partículas Semelhantes a Vírus/imunologia , Vacinas Virais/imunologia
18.
Front Immunol ; 12: 677027, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34168649

RESUMO

Epstein-Barr virus (EBV) is a human herpesvirus that is common among the global population, causing an enormous disease burden. EBV can directly cause infectious mononucleosis and is also associated with various malignancies and autoimmune diseases. In order to prevent primary infection and subsequent chronic disease, efforts have been made to develop a prophylactic vaccine against EBV in recent years, but there is still no vaccine in clinical use. The outbreak of the COVID-19 pandemic and the global cooperation in vaccine development against SARS-CoV-2 provide insights for next-generation antiviral vaccine design and opportunities for developing an effective prophylactic EBV vaccine. With improvements in antigen selection, vaccine platforms, formulation and evaluation systems, novel vaccines against EBV are expected to elicit dual protection against infection of both B lymphocytes and epithelial cells. This would provide sustainable immunity against EBV-associated malignancies, finally enabling the control of worldwide EBV infection and management of EBV-associated diseases.


Assuntos
Vacinas contra COVID-19/imunologia , COVID-19/imunologia , Infecções por Vírus Epstein-Barr/imunologia , Herpesvirus Humano 4/fisiologia , Transtornos Linfoproliferativos/imunologia , SARS-CoV-2/fisiologia , Vacinas Virais/imunologia , Animais , Infecções por Vírus Epstein-Barr/prevenção & controle , Humanos , Transtornos Linfoproliferativos/prevenção & controle , Profilaxia Pré-Exposição
19.
Viruses ; 13(5)2021 05 07.
Artigo em Inglês | MEDLINE | ID: mdl-34067226

RESUMO

The bluetongue virus (BTV) is transmitted by Culicoides biting midges and causes bluetongue (BT), an OIE-notifiable disease of ruminants. At least 29 BTV serotypes are described as determined by the outer shell proteins VP2 and VP5. Vaccination is the most effective control measure. Inactivated and live-attenuated vaccines (LAVs) are currently available. These vaccines have their specific pros and cons, and both are not DIVA vaccines. The BT Disabled Infectious Single Animal (DISA) vaccine platform is based on LAV without nonessential NS3/NS3a expression and is applicable for many serotypes by the exchange of outer shell proteins. The DISA vaccine is effective and completely safe. Further, transmission of the DISA vaccine by midges is blocked (DISA principle). Finally, the DISA vaccine enables DIVA because of a lack of antibodies against the immunogenic NS3/NS3a protein (DIVA principle). The deletion of 72 amino acids (72aa) in NS3/NS3a is sufficient to block virus propagation in midges. Here, we show that a prototype DISA vaccine based on LAV with the 72aa deletion enables DIVA, is completely safe and induces a long-lasting serotype-specific protection in cattle. In conclusion, the in-frame deletion of 72-aa codons in the BT DISA/DIVA vaccine platform is sufficient to fulfil all the criteria for modern veterinary vaccines.


Assuntos
Vírus Bluetongue/genética , Vírus Bluetongue/imunologia , Doenças dos Bovinos/prevenção & controle , Vacinas Atenuadas/imunologia , Proteínas não Estruturais Virais/imunologia , Vacinas Virais/imunologia , Animais , Anticorpos Antivirais/imunologia , Especificidade de Anticorpos , Bluetongue/prevenção & controle , Bluetongue/virologia , Bovinos , Genoma Viral , Imunização , Sorogrupo , Vacinas Virais/administração & dosagem , Vacinas Virais/efeitos adversos
20.
Res Vet Sci ; 138: 148-160, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34144282

RESUMO

The objective of this randomized, placebo-controlled, double-blinded field trial was to investigate the effects of oral administration of purple coneflower (Echinacea purpurea L. (EP)) on performance, health and immune parameters in calves. Calves (n = 27) were enrolled to three groups (9 calves per group): 0.5 g EP/calf per day (ECL), 5 g EP/calf per day (ECH) or placebo. Calves were vaccinated with Bluetongue-Virus (BTV) serotype 4 vaccine to investigate EPs effects on seroconversion. Clinical and performance parameters, inter alia body weight, health and milk intake were recorded for 57 days. Blood samples were analyzed for BTV antibodies and IgG by ELISA, white and red blood cell counts by flow cytometry and mRNA abundance of various inflammatory markers in leukocytes (IL-1ß, IL-8, tumor necrosis factor α (TNFα), cyclooxygenase 2 (Cox-2) and prostaglandin E synthase) was studied. The findings demonstrated no differences between groups regarding performance parameters. In all groups, calves suffered from diarrhea for a minimum of 2 days, but EP reduced the number of diarrhea days by 44% in ECL and increased the body temperature. Interestingly, ECL resulted in an increased number of respiratory disease days during the follow-up period. EP did not change blood cell and IgG counts, whereas eosinophil granulocytes were reduced in ECL. Decreased levels of hemoglobin and hematocrit were found in ECH. Prostaglandin E synthase levels in leukocytes were higher in ECL and ECH, whereas no differences were obtained for IL-1ß, IL-8, TNFα and Cox-2. Due to the unexpected occurrence of BTV seropositive calves before the first vaccination, 13 calves were excluded from the evaluation on seroconversion and no statistical analyses could be performed regarding antibody production. BTV-4 antibodies were not produced in 4 placebo-calves, whereas 4 of 5 and 1 of 6 ECL- and ECH-calves produced antibodies. Further investigations are needed to draw final conclusions on mode of action and efficacy of EP in calves.


Assuntos
Vírus Bluetongue/imunologia , Bovinos/fisiologia , Echinacea/química , Extratos Vegetais/administração & dosagem , Vacinação/veterinária , Vacinas Virais/imunologia , Animais , Bovinos/crescimento & desenvolvimento , Bovinos/imunologia , Método Duplo-Cego , Feminino , Masculino , Extratos Vegetais/química , Soroconversão
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