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2.
Int J Mol Sci ; 22(5)2021 Feb 28.
Artigo em Inglês | MEDLINE | ID: mdl-33670859

RESUMO

Adenovirus-based gene transfer vectors are the most frequently used vector type in gene therapy clinical trials to date, and they play an important role as genetic vaccine candidates during the ongoing SARS-CoV-2 pandemic. Immediately upon delivery, adenovirus-based vectors exhibit multiple complex vector-host interactions and induce innate and adaptive immune responses. This can severely limit their safety and efficacy, particularly after delivery through the blood stream. In this review article we summarize two strategies to modulate Ad vector-induced immune responses: extensive genomic and chemical capsid modifications. Both strategies have shown beneficial effects in a number of preclinical studies while potential synergistic effects warrant further investigations.


Assuntos
Adenoviridae/genética , Adenoviridae/imunologia , Capsídeo/imunologia , Vetores Genéticos/genética , Vetores Genéticos/imunologia , Animais , Proteínas do Capsídeo/genética , Humanos , Imunidade , Imunogenicidade da Vacina , /imunologia
3.
Viruses ; 13(2)2021 02 19.
Artigo em Inglês | MEDLINE | ID: mdl-33669550

RESUMO

Vaccine development against SARS-CoV-2 has been fierce due to the devastating COVID-19 pandemic and has included all potential approaches for providing the global community with safe and efficient vaccine candidates in the shortest possible timeframe. Viral vectors have played a central role especially using adenovirus-based vectors. Additionally, other viral vectors based on vaccinia viruses, measles viruses, rhabdoviruses, influenza viruses and lentiviruses have been subjected to vaccine development. Self-amplifying RNA virus vectors have been utilized for lipid nanoparticle-based delivery of RNA as COVID-19 vaccines. Several adenovirus-based vaccine candidates have elicited strong immune responses in immunized animals and protection against challenges in mice and primates has been achieved. Moreover, adenovirus-based vaccine candidates have been subjected to phase I to III clinical trials. Recently, the simian adenovirus-based ChAdOx1 vector expressing the SARS-CoV-2 S spike protein was approved for use in humans in the UK.


Assuntos
Adenoviridae/imunologia , Vetores Genéticos/imunologia , RNA Viral/imunologia , Vacinas Virais/imunologia , Animais , Anticorpos Antivirais/imunologia , Ensaios Clínicos como Assunto , Humanos , Camundongos , Pandemias
4.
Proc Natl Acad Sci U S A ; 118(12)2021 03 23.
Artigo em Inglês | MEDLINE | ID: mdl-33688034

RESUMO

The current pandemic of COVID-19 caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) highlights an urgent need to develop a safe, efficacious, and durable vaccine. Using a measles virus (rMeV) vaccine strain as the backbone, we developed a series of recombinant attenuated vaccine candidates expressing various forms of the SARS-CoV-2 spike (S) protein and its receptor binding domain (RBD) and evaluated their efficacy in cotton rat, IFNAR-/-mice, IFNAR-/--hCD46 mice, and golden Syrian hamsters. We found that rMeV expressing stabilized prefusion S protein (rMeV-preS) was more potent in inducing SARS-CoV-2-specific neutralizing antibodies than rMeV expressing full-length S protein (rMeV-S), while the rMeVs expressing different lengths of RBD (rMeV-RBD) were the least potent. Animals immunized with rMeV-preS produced higher levels of neutralizing antibody than found in convalescent sera from COVID-19 patients and a strong Th1-biased T cell response. The rMeV-preS also provided complete protection of hamsters from challenge with SARS-CoV-2, preventing replication in lungs and nasal turbinates, body weight loss, cytokine storm, and lung pathology. These data demonstrate that rMeV-preS is a safe and highly efficacious vaccine candidate, supporting its further development as a SARS-CoV-2 vaccine.


Assuntos
/imunologia , Vetores Genéticos , Vírus do Sarampo , Glicoproteína da Espícula de Coronavírus/imunologia , Vacinas Sintéticas/imunologia , Animais , Anticorpos Neutralizantes/imunologia , Anticorpos Antivirais/imunologia , /patologia , Cricetinae , Modelos Animais de Doenças , Expressão Gênica , Vetores Genéticos/genética , Vetores Genéticos/imunologia , Humanos , Imunização , Imunogenicidade da Vacina , Vírus do Sarampo/genética , Vírus do Sarampo/imunologia , Camundongos , Camundongos Transgênicos , Ratos , Glicoproteína da Espícula de Coronavírus/genética , Vacinas Sintéticas/genética
5.
Cell ; 184(6): 1589-1603, 2021 03 18.
Artigo em Inglês | MEDLINE | ID: mdl-33740454

RESUMO

Vaccines are critical tools for maintaining global health. Traditional vaccine technologies have been used across a wide range of bacterial and viral pathogens, yet there are a number of examples where they have not been successful, such as for persistent infections, rapidly evolving pathogens with high sequence variability, complex viral antigens, and emerging pathogens. Novel technologies such as nucleic acid and viral vector vaccines offer the potential to revolutionize vaccine development as they are well-suited to address existing technology limitations. In this review, we discuss the current state of RNA vaccines, recombinant adenovirus vector-based vaccines, and advances from biomaterials and engineering that address these important public health challenges.


Assuntos
/imunologia , /prevenção & controle , Vacinas Sintéticas/imunologia , Vacinas Sintéticas/uso terapêutico , Adenoviridae/genética , Animais , Antígenos Virais/genética , Materiais Biocompatíveis , Sistemas de Liberação de Medicamentos/métodos , Vetores Genéticos/imunologia , Humanos , Imunogenicidade da Vacina , Lipossomos , Nanopartículas , RNA Mensageiro/síntese química , RNA Mensageiro/imunologia
6.
Virology ; 557: 70-85, 2021 05.
Artigo em Inglês | MEDLINE | ID: mdl-33676349

RESUMO

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) emerged into the human population in late 2019 and caused the global COVID-19 pandemic. SARS-CoV-2 has spread to more than 215 countries and infected many millions of people. Despite the introduction of numerous governmental and public health measures to control disease spread, infections continue at an unabated pace, suggesting that effective vaccines and antiviral drugs will be required to curtail disease, end the pandemic, and restore societal norms. Here, we review the current developments in antibody and vaccine countermeasures to limit or prevent disease.


Assuntos
Anticorpos Antivirais/biossíntese , /prevenção & controle , Pandemias , /imunologia , Animais , /imunologia , /virologia , /biossíntese , Ensaios Clínicos como Assunto , Modelos Animais de Doenças , Vetores Genéticos/química , Vetores Genéticos/imunologia , Humanos , Imunidade Inata/efeitos dos fármacos , Imunização Passiva/métodos , Imunogenicidade da Vacina , Segurança do Paciente , /patogenicidade , Vacinas Atenuadas , Vacinas de DNA , Vacinas de Subunidades , Vacinas de Partículas Semelhantes a Vírus/administração & dosagem , Vacinas de Partículas Semelhantes a Vírus/biossíntese , Vacinas de Partículas Semelhantes a Vírus/imunologia
7.
J Virol ; 95(9)2021 04 12.
Artigo em Inglês | MEDLINE | ID: mdl-33627390

RESUMO

Current influenza vaccines, live attenuated or inactivated, do not protect against antigenically novel influenza A viruses (IAVs) of pandemic potential, which has driven interest in the development of universal influenza vaccines. Universal influenza vaccine candidates targeting highly conserved antigens of IAV nucleoprotein (NP) are promising as vaccines that induce T cell immunity, but concerns have been raised about the safety of inducing robust CD8 T cell responses in the lungs. Using a mouse model, we systematically evaluated effects of recombinant adenovirus vectors (rAd) expressing IAV NP (A/NP-rAd) or influenza B virus (IBV) NP (B/NP-rAd) on pulmonary inflammation and function after vaccination and following live IAV challenge. After A/NP-rAd or B/NP-rAd vaccination, female mice exhibited robust systemic and pulmonary vaccine-specific B cell and T cell responses and experienced no morbidity (e.g., body mass loss). Both in vivo pulmonary function testing and lung histopathology scoring revealed minimal adverse effects of intranasal rAd vaccination compared with unvaccinated mice. After IAV challenge, A/NP-rAd-vaccinated mice experienced significantly less morbidity, had lower pulmonary virus titers, and developed less pulmonary inflammation than unvaccinated or B/NP-rAd-vaccinated mice. Based on analysis of pulmonary physiology using detailed testing not previously applied to the question of T cell damage, mice protected by vaccination also had better lung function than controls. Results provide evidence that, in this model, adenoviral universal influenza vaccine does not damage pulmonary tissue. In addition, adaptive immunity, in particular, T cell immunity in the lungs, does not cause damage when restimulated but instead mitigates pulmonary damage following IAV infection.IMPORTANCE Respiratory viruses can emerge and spread rapidly before vaccines are available. It would be a tremendous advance to use vaccines that protect against whole categories of viruses, such as universal influenza vaccines, without the need to predict which virus will emerge. The nucleoprotein (NP) of influenza virus provides a target conserved among strains and is a dominant T cell target. In animals, vaccination to NP generates powerful T cell immunity and long-lasting protection against diverse influenza strains. Concerns have been raised, but not evaluated experimentally, that potent local T cell responses might damage the lungs. We analyzed lung function in detail in the setting of such a vaccination. Despite CD8 T cell responses in the lungs, lungs were not damaged and functioned normally after vaccination alone and were protected upon subsequent infection. This precedent provides important support for vaccines based on T cell-mediated protection, currently being considered for both influenza and SARS-CoV-2 vaccines.


Assuntos
Adenoviridae , Vetores Genéticos , Vírus da Influenza B , Vacinas contra Influenza , Pulmão , Infecções por Orthomyxoviridae , Adenoviridae/genética , Adenoviridae/imunologia , Animais , Linfócitos B/imunologia , Linfócitos B/patologia , Modelos Animais de Doenças , Feminino , Vetores Genéticos/genética , Vetores Genéticos/imunologia , Imunidade Celular , Vírus da Influenza B/genética , Vírus da Influenza B/imunologia , Vacinas contra Influenza/genética , Vacinas contra Influenza/imunologia , Pulmão/imunologia , Pulmão/patologia , Pulmão/virologia , Camundongos , Infecções por Orthomyxoviridae/genética , Infecções por Orthomyxoviridae/imunologia , Infecções por Orthomyxoviridae/patologia , Infecções por Orthomyxoviridae/prevenção & controle , Linfócitos T/imunologia , Linfócitos T/patologia
8.
Science ; 371(6528): 521-526, 2021 01 29.
Artigo em Inglês | MEDLINE | ID: mdl-33510029

RESUMO

Mucosal-associated invariant T (MAIT) cells are innate sensors of viruses and can augment early immune responses and contribute to protection. We hypothesized that MAIT cells may have inherent adjuvant activity in vaccine platforms that use replication-incompetent adenovirus vectors. In mice and humans, ChAdOx1 (chimpanzee adenovirus Ox1) immunization robustly activated MAIT cells. Activation required plasmacytoid dendritic cell (pDC)-derived interferon (IFN)-α and monocyte-derived interleukin-18. IFN-α-induced, monocyte-derived tumor necrosis factor was also identified as a key secondary signal. All three cytokines were required in vitro and in vivo. Activation of MAIT cells positively correlated with vaccine-induced T cell responses in human volunteers and MAIT cell-deficient mice displayed impaired CD8+ T cell responses to multiple vaccine-encoded antigens. Thus, MAIT cells contribute to the immunogenicity of adenovirus vectors, with implications for vaccine design.


Assuntos
Adenoviridae/imunologia , Imunogenicidade da Vacina , Células T Invariáveis Associadas à Mucosa/imunologia , Vacinas Virais/imunologia , Animais , Linfócitos T CD8-Positivos/imunologia , Células Dendríticas/imunologia , Vetores Genéticos/imunologia , Humanos , Interferon-alfa/metabolismo , Interleucina-18/metabolismo , Ativação Linfocitária , Camundongos , Camundongos Endogâmicos C57BL , Fator de Necrose Tumoral alfa/metabolismo
9.
J Immunol ; 206(5): 931-935, 2021 03 01.
Artigo em Inglês | MEDLINE | ID: mdl-33441437

RESUMO

The magnitude of SARS-CoV-2-specific T cell responses correlates inversely with human disease severity, suggesting T cell involvement in primary control. Whereas many COVID-19 vaccines focus on establishing humoral immunity to viral spike protein, vaccine-elicited T cell immunity may bolster durable protection or cross-reactivity with viral variants. To better enable mechanistic and vaccination studies in mice, we identified a dominant CD8 T cell SARS-CoV-2 nucleoprotein epitope. Infection of human ACE2 transgenic mice with SARS-CoV-2 elicited robust responses to H2-Db/N219-227, and 40% of HLA-A*02+ COVID-19 PBMC samples isolated from hospitalized patients responded to this peptide in culture. In mice, i.m. prime-boost nucleoprotein vaccination with heterologous vectors favored systemic CD8 T cell responses, whereas intranasal boosting favored respiratory immunity. In contrast, a single i.v. immunization with recombinant adenovirus established robust CD8 T cell memory both systemically and in the respiratory mucosa.


Assuntos
Linfócitos T CD8-Positivos/imunologia , /imunologia , Epitopos de Linfócito T/imunologia , Vacinação/métodos , /genética , Animais , Células Cultivadas , Modelos Animais de Doenças , Feminino , Vetores Genéticos/imunologia , Antígeno HLA-A2/imunologia , Humanos , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Transgênicos
10.
Methods Mol Biol ; 2183: 461-475, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-32959260

RESUMO

A hybrid biological-biomaterial vector composed of a biocompatible polymeric biomaterial coating and an Escherichia coli core was designed and developed for antigen delivery. It provides a unique and efficient mechanism to transport antigens (protein or genetic) via different mechanisms of vector design that include antigen cellular localization (cytoplasm, periplasm, cellular surface) and nonnative functionalities that assist in antigen delivery. Based on a variety of E. coli strain development and polymer chemistry tools, the hybrid vector can be constructed into a number of formats for the purpose of optimized uptake and processing by antigen presenting cells, serving as the basis for a potent subsequent immune response. This chapter serves to outline a protocol for assembling a hybrid biological-biomaterial vector for use as a vaccine delivery system.


Assuntos
Antígenos/administração & dosagem , Antígenos/imunologia , Vetores Genéticos/imunologia , Vacinas de DNA/administração & dosagem , Vacinas de DNA/imunologia , Animais , Antígenos de Bactérias/administração & dosagem , Antígenos de Bactérias/imunologia , Biofilmes , Sistemas de Liberação de Medicamentos , Expressão Gênica , Técnicas de Transferência de Genes , Vetores Genéticos/administração & dosagem , Vetores Genéticos/genética , Imunização , Plasmídeos/genética , Polímeros/química , Streptococcus pneumoniae/imunologia
11.
Methods Mol Biol ; 2197: 33-47, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-32827131

RESUMO

Alphavirus vectors have been engineered for high-level gene expression relying originally on replication-deficient recombinant particles, more recently designed for plasmid DNA-based administration. As alphavirus-based DNA vectors encode the alphavirus RNA replicon genes, enhanced transgene expression in comparison to conventional DNA plasmids is achieved. Immunization studies with alphavirus-based DNA plasmids have elicited specific antibody production, have generated tumor regression and protection against challenges with infectious agents and tumor cells in various animal models. A limited number of clinical trials have been conducted with alphavirus DNA vectors. Compared to conventional plasmid DNA-based immunization, alphavirus DNA vectors required 1000-fold less DNA to elicit similar immune responses in rodents.


Assuntos
Alphavirus/genética , Vetores Genéticos/genética , Plasmídeos/genética , Vacinas de DNA/genética , Vacinas de DNA/imunologia , Alphavirus/imunologia , Animais , Linhagem Celular , Modelos Animais de Doenças , Expressão Gênica , Genes Reporter , Vetores Genéticos/administração & dosagem , Vetores Genéticos/imunologia , Humanos , Imunização , Camundongos , Plasmídeos/administração & dosagem , Plasmídeos/imunologia , Suínos , Vacinação , Vacinas de DNA/administração & dosagem
12.
Nat Med ; 27(2): 279-288, 2021 02.
Artigo em Inglês | MEDLINE | ID: mdl-33335322

RESUMO

More than 190 vaccines are currently in development to prevent infection by the novel severe acute respiratory syndrome coronavirus 2. Animal studies suggest that while neutralizing antibodies against the viral spike protein may correlate with protection, additional antibody functions may also be important in preventing infection. Previously, we reported early immunogenicity and safety outcomes of a viral vector coronavirus vaccine, ChAdOx1 nCoV-19 (AZD1222), in a single-blinded phase 1/2 randomized controlled trial of healthy adults aged 18-55 years ( NCT04324606 ). Now we describe safety and exploratory humoral and cellular immunogenicity of the vaccine, from subgroups of volunteers in that trial, who were subsequently allocated to receive a homologous full-dose (SD/SD D56; n = 20) or half-dose (SD/LD D56; n = 32) ChAdOx1 booster vaccine 56 d following prime vaccination. Previously reported immunogenicity data from the open-label 28-d interval prime-boost group (SD/SD D28; n = 10) are also presented to facilitate comparison. Additionally, we describe volunteers boosted with the comparator vaccine (MenACWY; n = 10). In this interim report, we demonstrate that a booster dose of ChAdOx1 nCoV-19 is safe and better tolerated than priming doses. Using a systems serology approach we also demonstrate that anti-spike neutralizing antibody titers, as well as Fc-mediated functional antibody responses, including antibody-dependent neutrophil/monocyte phagocytosis, complement activation and natural killer cell activation, are substantially enhanced by a booster dose of vaccine. A booster dose of vaccine induced stronger antibody responses than a dose-sparing half-dose boost, although the magnitude of T cell responses did not increase with either boost dose. These data support the two-dose vaccine regime that is now being evaluated in phase 3 clinical trials.


Assuntos
Formação de Anticorpos/imunologia , /imunologia , Imunização Secundária , /imunologia , Adolescente , Adulto , Anticorpos Neutralizantes/imunologia , Relação Dose-Resposta a Droga , Vetores Genéticos/imunologia , Humanos , Pessoa de Meia-Idade , Glicoproteína da Espícula de Coronavírus/imunologia , Fatores de Tempo , Adulto Jovem
13.
Methods Mol Biol ; 2197: 285-304, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-32827144

RESUMO

DNA vaccines have been used as a promising strategy for delivery of immunogenic and immunomodulatory molecules into the host cells. Although, there are some obstacles involving the capability of the plasmid vector to reach the cell nucleus in great number to promote the expected benefits. In order to improve the delivery and, consequently, increase the expression levels of the target proteins carried by DNA vaccines, alternative methodologies have been explored, including the use of non-pathogenic bacteria as delivery vectors to carry, deliver, and protect the DNA from degradation, enhancing plasmid expression.


Assuntos
DNA/genética , Vetores Genéticos/genética , Lactobacillales/genética , Plasmídeos/genética , DNA/imunologia , DNA/isolamento & purificação , Escherichia coli/genética , Técnicas de Transferência de Genes , Vetores Genéticos/administração & dosagem , Vetores Genéticos/imunologia , Vetores Genéticos/isolamento & purificação , Humanos , Plasmídeos/administração & dosagem , Plasmídeos/imunologia , Plasmídeos/isolamento & purificação , Transfecção , Transformação Bacteriana , Vacinas de DNA/administração & dosagem , Vacinas de DNA/genética , Vacinas de DNA/imunologia
14.
Nat Rev Immunol ; 20(10): 615-632, 2020 10.
Artigo em Inglês | MEDLINE | ID: mdl-32887954

RESUMO

The coronavirus disease 2019 (COVID-19) pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the most formidable challenge to humanity in a century. It is widely believed that prepandemic normalcy will never return until a safe and effective vaccine strategy becomes available and a global vaccination programme is implemented successfully. Here, we discuss the immunological principles that need to be taken into consideration in the development of COVID-19 vaccine strategies. On the basis of these principles, we examine the current COVID-19 vaccine candidates, their strengths and potential shortfalls, and make inferences about their chances of success. Finally, we discuss the scientific and practical challenges that will be faced in the process of developing a successful vaccine and the ways in which COVID-19 vaccine strategies may evolve over the next few years.


Assuntos
Anticorpos Antivirais/biossíntese , Betacoronavirus/imunologia , Infecções por Coronavirus/prevenção & controle , Pandemias/prevenção & controle , Pneumonia Viral/prevenção & controle , Síndrome Respiratória Aguda Grave/epidemiologia , Síndrome Respiratória Aguda Grave/prevenção & controle , Vacinas Virais/imunologia , Betacoronavirus/efeitos dos fármacos , Betacoronavirus/patogenicidade , Ensaios Clínicos como Assunto , Infecções por Coronavirus/epidemiologia , Infecções por Coronavirus/imunologia , Infecções por Coronavirus/virologia , Vetores Genéticos/química , Vetores Genéticos/imunologia , Humanos , Imunidade Coletiva/efeitos dos fármacos , Imunidade Inata/efeitos dos fármacos , Esquemas de Imunização , Imunogenicidade da Vacina , Segurança do Paciente , Pneumonia Viral/epidemiologia , Pneumonia Viral/imunologia , Pneumonia Viral/virologia , Síndrome Respiratória Aguda Grave/imunologia , Síndrome Respiratória Aguda Grave/virologia , Vacinas Atenuadas , Vacinas de DNA , Vacinas de Subunidades , Vacinas de Partículas Semelhantes a Vírus , Vacinas Virais/administração & dosagem , Vacinas Virais/biossíntese
15.
Virus Res ; 288: 198114, 2020 10 15.
Artigo em Inglês | MEDLINE | ID: mdl-32800805

RESUMO

The current COVID-19 pandemic has urged the scientific community internationally to find answers in terms of therapeutics and vaccines to control SARS-CoV-2. Published investigations mostly on SARS-CoV and to some extent on MERS has taught lessons on vaccination strategies to this novel coronavirus. This is attributed to the fact that SARS-CoV-2 uses the same receptor as SARS-CoV on the host cell i.e. human Angiotensin Converting Enzyme 2 (hACE2) and is approximately 79% similar genetically to SARS-CoV. Though the efforts on COVID-19 vaccines started very early, initially in China, as soon as the outbreak of novel coronavirus erupted and then world-over as the disease was declared a pandemic by WHO. But we will not be having an effective COVID-19 vaccine before September, 2020 as per very optimistic estimates. This is because a successful COVID-19 vaccine will require a cautious validation of efficacy and adverse reactivity as the target vaccinee population include high-risk individuals over the age of 60, particularly those with chronic co-morbid conditions, frontline healthcare workers and those involved in essentials industries. Various platforms for vaccine development are available namely: virus vectored vaccines, protein subunit vaccines, genetic vaccines, and monoclonal antibodies for passive immunization which are under evaluations for SARS-CoV-2, with each having discrete benefits and hindrances. The COVID-19 pandemic which probably is the most devastating one in the last 100 years after Spanish flu mandates the speedy evaluation of the multiple approaches for competence to elicit protective immunity and safety to curtail unwanted immune-potentiation which plays an important role in the pathogenesis of this virus. This review is aimed at providing an overview of the efforts dedicated to an effective vaccine for this novel coronavirus which has crippled the world in terms of economy, human health and life.


Assuntos
Anticorpos Antivirais/biossíntese , Betacoronavirus/imunologia , Infecções por Coronavirus/prevenção & controle , Pandemias/prevenção & controle , Pneumonia Viral/prevenção & controle , Vacinas Virais/imunologia , Betacoronavirus/efeitos dos fármacos , Betacoronavirus/patogenicidade , Ensaios Clínicos como Assunto , Infecções por Coronavirus/epidemiologia , Infecções por Coronavirus/imunologia , Infecções por Coronavirus/terapia , Infecções por Coronavirus/virologia , Vetores Genéticos/química , Vetores Genéticos/imunologia , Humanos , Imunidade Inata/efeitos dos fármacos , Imunização Passiva/métodos , Imunogenicidade da Vacina , Segurança do Paciente , Peptidil Dipeptidase A/genética , Peptidil Dipeptidase A/imunologia , Peptidil Dipeptidase A/metabolismo , Pneumonia Viral/epidemiologia , Pneumonia Viral/imunologia , Pneumonia Viral/virologia , Receptores Virais/genética , Receptores Virais/imunologia , Receptores Virais/metabolismo , Vacinas Atenuadas , Vacinas de DNA , Vacinas de Subunidades , Vacinas de Partículas Semelhantes a Vírus/administração & dosagem , Vacinas de Partículas Semelhantes a Vírus/biossíntese , Vacinas de Partículas Semelhantes a Vírus/imunologia , Vacinas Virais/administração & dosagem , Vacinas Virais/biossíntese
16.
Virus Res ; 288: 198141, 2020 10 15.
Artigo em Inglês | MEDLINE | ID: mdl-32846196

RESUMO

The recent outbreak of the betacoronavirus SARS-CoV-2 has become a significant concern to public health care worldwide. As of August 19, 2020, more than 22,140,472 people are infected, and over 781,135 people have died due to this deadly virus. In the USA alone, over 5,482,602 people are currently infected, and more than 171,823 people have died. SARS-CoV-2 has shown a higher infectivity rate and a more extended incubation period as compared to previous coronaviruses. SARS-CoV-2 binds much more strongly than SARS-CoV to the same host receptor, angiotensin-converting enzyme 2 (ACE2). Previously, several methods to develop a vaccine against SARS-CoV or MERS-CoV have been tried with limited success. Since SARS-CoV-2 uses the spike (S) protein for entry to the host cell, it is one of the most preferred targets for making vaccines or therapeutics against SARS-CoV-2. In this review, we have summarised the characteristics of the S protein, as well as the different approaches being used for the development of vaccines and/or therapeutics based on the S protein.


Assuntos
Anticorpos Antivirais/biossíntese , Betacoronavirus/imunologia , Infecções por Coronavirus/prevenção & controle , Pandemias/prevenção & controle , Pneumonia Viral/prevenção & controle , Glicoproteína da Espícula de Coronavírus/imunologia , Vacinas Virais/imunologia , Anticorpos Facilitadores/efeitos dos fármacos , Betacoronavirus/efeitos dos fármacos , Betacoronavirus/patogenicidade , Ensaios Clínicos como Assunto , Infecções por Coronavirus/epidemiologia , Infecções por Coronavirus/imunologia , Infecções por Coronavirus/virologia , Vetores Genéticos/química , Vetores Genéticos/imunologia , Humanos , Imunogenicidade da Vacina , Segurança do Paciente , Peptidil Dipeptidase A/genética , Peptidil Dipeptidase A/imunologia , Peptidil Dipeptidase A/metabolismo , Pneumonia Viral/epidemiologia , Pneumonia Viral/imunologia , Pneumonia Viral/virologia , Receptores Virais/genética , Receptores Virais/imunologia , Receptores Virais/metabolismo , Glicoproteína da Espícula de Coronavírus/genética , Glicoproteína da Espícula de Coronavírus/metabolismo , Vacinas Atenuadas , Vacinas de DNA , Vacinas de Subunidades , Vacinas de Partículas Semelhantes a Vírus/administração & dosagem , Vacinas de Partículas Semelhantes a Vírus/biossíntese , Vacinas de Partículas Semelhantes a Vírus/imunologia , Vacinas Virais/administração & dosagem , Vacinas Virais/biossíntese
17.
PLoS Pathog ; 16(6): e1008522, 2020 06.
Artigo em Inglês | MEDLINE | ID: mdl-32589686

RESUMO

DNA vectors have been widely used as a priming of poxvirus vaccine in prime/boost regimens. Whether the number of DNA impacts qualitatively or quantitatively the immune response is not fully explored. With the aim to reinforce T-cell responses by optimizing the prime-boost regimen, the multicentric EV03/ANRS VAC20 phase I/II trial, randomized 147 HIV-negative volunteers to either 3xDNA plus 1xNYVAC (weeks 0, 4, 8 plus 24; n = 74) or to 2xDNA plus 2xNYVAC (weeks 0, 4 plus 20, 24; n = 73) groups. T-cell responses (IFN-γ ELISPOT) to at least one peptide pool were higher in the 3xDNA than the 2xDNA groups (91% and 80% of vaccinees) (P = 0.049). In the 3xDNA arm, 26 (37%) recipients developed a broader T-cell response (Env plus at least to one of the Gag, Pol, Nef pools) than in the 2xDNA (15; 22%) arms (primary endpoint; P = 0.047) with a higher magnitude against Env (at week 26) (P<0.001). In both groups, vaccine regimens induced HIV-specific polyfunctional CD4 and CD8 T cells and the production of Th1, Th2 and Th17/IL-21 cytokines. Antibody responses were also elicited in up to 81% of vaccines. A higher percentage of IgG responders was noted in the 2xDNA arm compared to the 3xDNA arm, while the 3xDNA group tended to elicit a higher magnitude of IgG3 response against specific Env antigens. We show here that the modulation of the prime strategy, without modifying the route or the dose of administration, or the combination of vectors, may influence the quality of the responses.


Assuntos
Vacinas contra a AIDS/imunologia , Vetores Genéticos/imunologia , Antígenos HIV/imunologia , Poxviridae/imunologia , Vacinas de DNA/imunologia , Produtos do Gene env do Vírus da Imunodeficiência Humana/imunologia , Vacinas contra a AIDS/administração & dosagem , Vacinas contra a AIDS/genética , Adolescente , Adulto , Linfócitos T CD8-Positivos/imunologia , Feminino , Vetores Genéticos/administração & dosagem , Vetores Genéticos/genética , Antígenos HIV/administração & dosagem , Antígenos HIV/genética , Humanos , Interferon gama/imunologia , Masculino , Pessoa de Meia-Idade , Poxviridae/genética , Linfócitos T Auxiliares-Indutores/metabolismo , Vacinas de DNA/administração & dosagem , Vacinas de DNA/genética , Produtos do Gene env do Vírus da Imunodeficiência Humana/administração & dosagem , Produtos do Gene env do Vírus da Imunodeficiência Humana/genética
18.
Mem Inst Oswaldo Cruz ; 115: e190347, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32428188

RESUMO

BACKGROUND Bacillus Calmette-Guérin (BCG) is considered a promising live bacterial delivery system. However, several proposals for rBCG vaccines have not progressed, mainly due to the limitations of the available expression systems. OBJECTIVES To obtain a set of mycobacterial vectors using a range of promoters with different strengths based on a standard backbone, previously shown to be stable. METHODS Mycobacterial expression vectors based on the pLA71 vector as backbone, were obtained inserting different promoters (PAN, PαAg, PHsp60, PBlaF* and PL5) and the green fluorescence protein (GFP) as reporter gene, to evaluate features such as their relative strengths, and the in vitro (inside macrophages) and in vivo stability. FINDINGS The relative fluorescence observed with the different vectors showed increasing strength of the promoters: PAN was the weakest in both Mycobacterium smegmatis and BCG and PBlaF* was higher than PHsp60 in BCG. The relative fluorescence observed in a macrophage cell line showed that PBlaF* and PHsp60 were comparable. It was not possible to obtain strains transformed with the extrachromosomal expression vector containing the PL5 in either species. MAIN CONCLUSION We have obtained a set of potentially stable mycobacterial vectors with a arrange of expression levels, to be used in the development of rBCG vaccines.


Assuntos
Vacina BCG/imunologia , Escherichia coli/imunologia , Vetores Genéticos/imunologia , Proteínas de Fluorescência Verde/imunologia , Mycobacterium bovis/imunologia , Mycobacterium smegmatis/imunologia , Animais , Escherichia coli/genética , Feminino , Vetores Genéticos/genética , Camundongos , Camundongos Endogâmicos BALB C
19.
Mol Biotechnol ; 62(5): 289-296, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-32185600

RESUMO

Pasteurella multocida is the main cause of haemorrhagic septicaemia (HS) outbreak in livestock, such as cattle and buffaloes. Conventional vaccines such as alum-precipitated or oil-adjuvant broth bacterins were injected subcutaneously to provide protection against HS. However, the immunity developed is only for short term and needed to be administered frequently. In our previous study, a short gene fragment from Pasteurella multocida serotype B was obtained via shotgun cloning technique and later was cloned into bacterial expression system. pQE32-ABA392 was found to possess immunogenic activity towards HS when tested in vivo in rat model. In this study, the targeted gene fragment of ABA392 was sub-cloned into a DNA expression vector pVAX1 and named as pVAX1-ABA392. The new recombinant vaccine was stable and expressed on mammalian cell lines. Serum sample collected from a group of vaccinated rats for ELISA test shows that the antibody in immunized rats was present at high titer and can be tested as a vaccine candidate with challenge in further studies. This successful recombinant vaccine is immunogenic and potentially could be used as vaccine in future against HS.


Assuntos
DNA Bacteriano/genética , Septicemia Hemorrágica/microbiologia , Infecções por Pasteurella/prevenção & controle , Pasteurella multocida/genética , Vacinas de DNA/administração & dosagem , Animais , Clonagem Molecular , DNA Bacteriano/imunologia , Modelos Animais de Doenças , Feminino , Vetores Genéticos/administração & dosagem , Vetores Genéticos/imunologia , Septicemia Hemorrágica/prevenção & controle , Pasteurella multocida/imunologia , Plasmídeos/genética , Ratos , Análise de Sequência de DNA , Vacinação , Vacinas de DNA/imunologia
20.
Sci Rep ; 10(1): 2221, 2020 02 10.
Artigo em Inglês | MEDLINE | ID: mdl-32042001

RESUMO

Highly pathogenic avian influenza (HPAI) is a devastating disease of poultry and a serious threat to public health. Vaccination with inactivated virus vaccines has been applied for several years as one of the major policies to control highly pathogenic avian influenza virus (HPAIV) infections in chickens. Viral-vectored HA protein vaccines are a desirable alternative for inactivated vaccines. However, each viral vector possesses its own advantages and disadvantages for the development of a HA-based vaccine against HPAIV. Recombinant Newcastle disease virus (rNDV) strain LaSota expressing HA protein vaccine has shown promising results against HPAIV; however, its replication is restricted only to the respiratory tract. Therefore, we thought to evaluate avian paramyxovirus serotype 3 (APMV-3) strain Netherlands as a safe vaccine vector against HPAIV, which has high efficiency replication in a greater range of host organs. In this study, we generated rAPMV-3 expressing the HA protein of H5N1 HPAIV using reverse genetics and evaluated the induction of neutralizing antibodies and protection by rAPMV3 and rNDV expressing the HA protein against HPAIV challenge in chickens. Our results showed that immunization of chickens with rAPMV-3 or rNDV expressing HA protein provided complete protection against HPAIV challenge. However, immunization of chickens with rAPMV-3 expressing HA protein induced higher level of neutralizing antibodies compared to that of rNDV expressing HA protein. These results suggest that a rAPMV-3 expressing HA protein might be a better vaccine for mass-vaccination of commercial chickens in field conditions.


Assuntos
Avulavirus/imunologia , Glicoproteínas de Hemaglutininação de Vírus da Influenza/imunologia , Virus da Influenza A Subtipo H5N1/patogenicidade , Vacinas contra Influenza/imunologia , Influenza Aviária/prevenção & controle , Criação de Animais Domésticos , Animais , Anticorpos Neutralizantes/análise , Anticorpos Neutralizantes/imunologia , Anticorpos Antivirais/análise , Anticorpos Antivirais/imunologia , Avulavirus/genética , Galinhas , Vetores Genéticos/genética , Vetores Genéticos/imunologia , Imunogenicidade da Vacina , Vacinas contra Influenza/administração & dosagem , Vacinas contra Influenza/genética , Influenza Aviária/virologia , Vacinas Sintéticas/administração & dosagem , Vacinas Sintéticas/genética , Vacinas Sintéticas/imunologia
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