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1.
Vet Res ; 52(1): 139, 2021 Nov 12.
Artigo em Inglês | MEDLINE | ID: mdl-34772449

RESUMO

Chicken immune responses to infectious bronchitis virus (IBV) vaccination can depend on route of administration, vaccine strain and bird age. Typically for layer chickens, IBV vaccinations are administered by spray in the hatchery at day-old and boosted at intervals with live vaccines via drinking water (DW). Knowledge of live attenuated IBV vaccine virus kinetics and the immune response in egg-laying hens is exceptionally limited. Here, we demonstrated dissemination of vaccine viruses and differences in hen innate, mucosal, cellular and humoral immune responses following vaccination with Massachusetts or 793B strains, administered by DW or oculonasal (ON) routes. Detection of IBV in the Mass-vaccinated groups was greater during early time-points, however, 793B was detected more frequently at later timepoints. Viral RNA loads in the Harderian gland and turbinate tissues were significantly higher for ON-Mass compared to all other vaccinated groups. Lachrymal fluid IgY levels were significantly greater than the control at 14 days post-vaccination (dpv) for both vaccine serotypes, and IgA mRNA levels were significantly greater in ON-vaccinated groups compared to DW-vaccinated groups, demonstrating robust mucosal immune responses. Cell mediated immune gene transcripts (CD8-α and CD8-ß) were up-regulated in turbinate and trachea tissues. For both vaccines, dissemination and vaccine virus clearance was slower when given by DW compared to the ON route. For ON administration, both vaccines induced comparable levels of mucosal immunity. The Mass vaccine induced cellular immunity to similar levels regardless of vaccination method. When given either by ON or DW, 793B vaccination induced significantly higher levels of humoral immunity.


Assuntos
Galinhas/imunologia , Infecções por Coronavirus/veterinária , Doenças das Aves Domésticas/imunologia , Vacinas Virais/imunologia , Animais , Anticorpos Antivirais/imunologia , Infecções por Coronavirus/imunologia , Feminino , Imunidade Celular , Imunidade Humoral , Imunidade nas Mucosas , Vírus da Bronquite Infecciosa , Doenças das Aves Domésticas/virologia , Vacinação/veterinária , Vacinas Atenuadas/imunologia
2.
Trials ; 22(1): 724, 2021 Oct 21.
Artigo em Inglês | MEDLINE | ID: mdl-34674742

RESUMO

BACKGROUND: Late 2019, a new highly contagious coronavirus SARS-CoV-2 has emerged in Wuhan, China, causing within 2 months a pandemic with the highest disease burden in elderly and people with pre-existing medical conditions. The pandemic has highlighted that new and more flexible clinical trial approaches, such as trial platforms, are needed to assess the efficacy and safety of interventions in a timely manner. The two existing Swiss cohorts of immunocompromised patients (i.e., Swiss HIV Cohort Study (SHCS) and Swiss Transplant Cohort Study (STCS)) are an ideal foundation to set-up a trial platform in Switzerland leveraging routinely collected data. Within a newly founded trial platform, we plan to assess the efficacy of the first two mRNA SARS-CoV-2 vaccines that reached market authorization in Switzerland in the frame of a pilot randomized controlled trial (RCT) while at the same time assessing the functionality of the trial platform. METHODS: We will conduct a multicenter randomized controlled, open-label, 2-arm sub-study pilot trial of a platform trial nested into two Swiss cohorts. Patients included in the SHCS or the STCS will be eligible for randomization to either receiving the mRNA vaccine Comirnaty® (Pfizer/BioNTech) or the COVID-19 mRNA Vaccine Moderna®. The primary clinical outcome will be change in pan-lg antibody response (pan-Ig anti-S1-RBD; baseline vs. 3 months after first vaccination; binary outcome, considering ≥ 0.8 units/ml as a positive antibody response). The pilot study will also enable us to assess endpoints related to trial conduct feasibility (i.e., duration of RCT set-up; time of patient recruitment; patient consent rate; proportion of missing data). Assuming vaccine reactivity of 90% in both vaccine groups, we power our trial, using a non-inferiority margin such that a 95% two-sided confidence interval excludes a difference in favor of the reference group of more than 10%. A sample size of 380 (190 in each treatment arm) is required for a statistical power of 90% and a type I error of 0.025. The study is funded by the Swiss National Science Foundation (National Research Program NRP 78, "COVID-19"). DISCUSSION: This study will provide crucial information about the efficacy and safety of the mRNA SARS-CoV-2 vaccines in HIV patients and organ transplant recipients. Furthermore, this project has the potential to pave the way for further platform trials in Switzerland. TRIAL REGISTRATION: ClinicalTrials.gov NCT04805125 . Registered on March 18, 2021.


Assuntos
COVID-19 , Vacinas Virais , Idoso , Vacinas contra COVID-19 , Humanos , Hospedeiro Imunocomprometido , Estudos Multicêntricos como Assunto , Projetos Piloto , RNA Mensageiro , Ensaios Clínicos Controlados Aleatórios como Assunto , SARS-CoV-2
3.
Proc Natl Acad Sci U S A ; 118(43)2021 10 26.
Artigo em Inglês | MEDLINE | ID: mdl-34686605

RESUMO

Self-amplifying RNA replicons are promising platforms for vaccine generation. Their defects in one or more essential functions for viral replication, particle assembly, or dissemination make them highly safe as vaccines. We previously showed that the deletion of the envelope (E) gene from the Middle East respiratory syndrome coronavirus (MERS-CoV) produces a replication-competent propagation-defective RNA replicon (MERS-CoV-ΔE). Evaluation of this replicon in mice expressing human dipeptidyl peptidase 4, the virus receptor, showed that the single deletion of the E gene generated an attenuated mutant. The combined deletion of the E gene with accessory open reading frames (ORFs) 3, 4a, 4b, and 5 resulted in a highly attenuated propagation-defective RNA replicon (MERS-CoV-Δ[3,4a,4b,5,E]). This RNA replicon induced sterilizing immunity in mice after challenge with a lethal dose of a virulent MERS-CoV, as no histopathological damage or infectious virus was detected in the lungs of challenged mice. The four mutants lacking the E gene were genetically stable, did not recombine with the E gene provided in trans during their passage in cell culture, and showed a propagation-defective phenotype in vivo. In addition, immunization with MERS-CoV-Δ[3,4a,4b,5,E] induced significant levels of neutralizing antibodies, indicating that MERS-CoV RNA replicons are highly safe and promising vaccine candidates.


Assuntos
Infecções por Coronavirus/prevenção & controle , Coronavírus da Síndrome Respiratória do Oriente Médio/genética , Coronavírus da Síndrome Respiratória do Oriente Médio/imunologia , RNA Viral/administração & dosagem , Replicon , Vacinas Virais/administração & dosagem , Animais , Anticorpos Neutralizantes/biossíntese , Anticorpos Antivirais/biossíntese , Infecções por Coronavirus/genética , Infecções por Coronavirus/imunologia , Infecções por Coronavirus/virologia , Vírus Defeituosos/genética , Vírus Defeituosos/imunologia , Feminino , Deleção de Genes , Genes env , Humanos , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Transgênicos , Coronavírus da Síndrome Respiratória do Oriente Médio/patogenicidade , RNA Viral/genética , RNA Viral/imunologia , Vacinas de Partículas Semelhantes a Vírus/administração & dosagem , Vacinas de Partículas Semelhantes a Vírus/genética , Vacinas de Partículas Semelhantes a Vírus/imunologia , Vacinas Virais/genética , Vacinas Virais/imunologia , Virulência/genética , Virulência/imunologia
5.
Front Immunol ; 12: 666594, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34630378

RESUMO

Coxsackievirus B3 (CVB3)-induced viral myocarditis is a common clinical cardiovascular disease without effective available vaccine. In this study, we tried to potentiate the immunoprotection efficacy of our previous CVB3-specific VP1 protein vaccine by introducing a streptococcal protein G-derived, draining lymph nodes (dLNs)-targeting albumin-binding domain (ABD) peptide. We found that compared with the original VP1 vaccine, ABD-fused VP1 (ABD-VP1) vaccine gained the new ability to efficiently bind murine albumin both in vitro and in vivo, possessed a much longer serum half-life in serum and exhibited more abundance in the dLNs after immunization. Accordingly, ABD-VP1 immunization not only significantly facilitated the enrichment and maturation of dendritic cells (DCs), induced higher percentages of IFN-γ+ CD8 + cells in the dLNs, but also robustly promoted VP1-induced T cell proliferation and cytotoxic T lymphocyte (CTL) responses in the spleens. More importantly, ABD-VP1 also elicited higher percentages of protective CD44hi CD62Lhi memory T cells in dLNs and spleens. Consequently, obvious protective effect against viral myocarditis was conferred by ABD-VP1 vaccine compared to the VP1 vaccine, reflected by the less body weight loss, improved cardiac function, alleviated cardiac histomorphological changes and an increased 28-day survival rate. Our results indicated that the ABD might be a promising immune-enhancing regime for vaccine design and development.


Assuntos
Proteínas de Bactérias/administração & dosagem , Proteínas do Capsídeo/administração & dosagem , Infecções por Coxsackievirus/prevenção & controle , Enterovirus Humano B/imunologia , Imunogenicidade da Vacina , Miocardite/prevenção & controle , Fragmentos de Peptídeos/administração & dosagem , Albumina Sérica/metabolismo , Vacinas Virais/administração & dosagem , Animais , Proteínas de Bactérias/imunologia , Proteínas de Bactérias/metabolismo , Proteínas do Capsídeo/imunologia , Proteínas do Capsídeo/metabolismo , Infecções por Coxsackievirus/imunologia , Infecções por Coxsackievirus/metabolismo , Infecções por Coxsackievirus/virologia , Modelos Animais de Doenças , Células HeLa , Humanos , Imunização , Masculino , Camundongos Endogâmicos BALB C , Miocardite/imunologia , Miocardite/metabolismo , Miocardite/virologia , Fragmentos de Peptídeos/imunologia , Fragmentos de Peptídeos/metabolismo , Ligação Proteica , Domínios e Motivos de Interação entre Proteínas , Vacinas Sintéticas/administração & dosagem , Vacinas Sintéticas/imunologia , Vacinas Sintéticas/metabolismo , Vacinas Virais/imunologia , Vacinas Virais/metabolismo
6.
Yonsei Med J ; 62(11): 961-968, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-34672129

RESUMO

Since the COVID-19 pandemic first began in December 2019, the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus has continuously evolved with many variants emerging across the world. These variants are categorized as the variant of interest (VOI), variant of concern (VOC), and variant under monitoring (VUM). As of September 15, 2021, there are four SARS-CoV-2 lineages designated as the VOC (alpha, beta, gamma, and delta variants). VOCs have increased transmissibility compared to the original virus, and have the potential for increasing disease severity. In addition, VOCs exhibit decreased susceptibility to vaccine-induced and infection-induced immune responses, and thus possess the ability to reinfect previously infected and recovered individuals. Given their ability to evade immune responses, VOC are less susceptible to monoclonal antibody treatments. VOCs can also impact the effectiveness of mRNA and adenovirus vector vaccines, although the currently authorized COVID-19 vaccines are still effective in preventing infection and severe disease. Current measures to reduce transmission as well as efforts to monitor and understand the impact of variants should be continued. Here, we review the molecular features, epidemiology, impact on transmissibility, disease severity, and vaccine effectiveness of VOCs.


Assuntos
COVID-19 , Vacinas Virais , Vacinas contra COVID-19 , Humanos , Pandemias , SARS-CoV-2
7.
Biomed Res Int ; 2021: 7251119, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34651048

RESUMO

Background: B.1.617.1, a variant of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) causing respiratory illness is responsible for the second wave of COVID-19 and associated with a high incidence of infectivity and mortality. To mitigate the B.1.617.1 variant of SARS-CoV-2, deciphering the protein structure and immunological responses by employing bioinformatics tools for data mining and analysis is pivotal. Objectives: Here, an in silico approach was employed for deciphering the structure and immune function of the subunit of spike (S) protein of SARS-CoV-2 B.1.617.1 variant. Methods: The partial amino acid sequence of SARS-CoV-2 B.1.617.1 variant S protein was analyzed, and its putative secondary and tertiary structure was predicted. Immunogenic analyses including B- and T-cell epitopes, interferon-gamma (IFN-γ) response, chemokine, and protective antigens for SARS-CoV 2 S proteins were predicted using appropriate tools. Results: B.1.617.1 variant S protein sequence was found to be highly stable and amphipathic. ABCpred and CTLpred analyses led to the identification of two potential antigenic B cell and T cell epitopes with starting amino acid positions at 60 and 82 (for B cell epitopes) and 54 and 98 (for T cell epitopes) having prediction scores > 0.8. Further, RAMPAGE tool was used for determining the allowed and disallowed regions of the three-dimensional predicted structure of SARS-CoV-2 B.1.617.1 variant S protein. Conclusion: Together, the in silico analysis revealed the predicted structure of partial S protein, immunogenic properties, and possible regions for S protein of SARS-CoV-2 and provides a valuable prelude for engineering the targeted vaccine or drug against B.1.617.1 variant of SARS-CoV-2.


Assuntos
Vacinas contra COVID-19/imunologia , COVID-19/virologia , SARS-CoV-2/imunologia , Glicoproteína da Espícula de Coronavírus/imunologia , Algoritmos , Sequência de Aminoácidos , COVID-19/imunologia , COVID-19/metabolismo , Biologia Computacional/métodos , Epitopos de Linfócito B/imunologia , Epitopos de Linfócito T/imunologia , Humanos , Imunogenicidade da Vacina , Ligação Proteica , Glicoproteína da Espícula de Coronavírus/metabolismo , Relação Estrutura-Atividade , Vacinas Virais/imunologia
8.
BMC Genomics ; 22(1): 777, 2021 Oct 30.
Artigo em Inglês | MEDLINE | ID: mdl-34717548

RESUMO

BACKGROUND: Viral vectors, including adenovirus (Ad) and modified vaccinia Ankara (MVA), have gained increasing attention as vaccine platforms in recent years due to their capacity to express antigens from a wide array of pathogens, their rapid induction of humoral and cellular protective immune responses, and their relatively low production costs. In particular, the chimpanzee Ad vector, ChAdOx1, has taken centre stage as a leading COVID-19 vaccine candidate. However, despite mounting data, both clinical and pre-clinical, demonstrating effective induction of adaptive immune responses, the innate immune signals that precede the protective responses that make these vectors attractive vaccine platforms remain poorly understood. RESULTS: In this study, a mouse immunisation model was used to evaluate whole blood gene expression changes 24 h after either a single dose or heterologous prime-boost regimen of an Ad and/or MVA vaccine. We demonstrate through comparative analysis of Ad vectors encoding different antigens that a transgene product-specific gene signature can be discerned from the vector-induced transcriptional response. Expression of genes involved in TLR2 stimulation and γδ T cell and natural killer cell activation were induced after a single dose of Ad, while MVA led to greater expression of type I interferon genes. The order of prime-boost combinations was found to influence the magnitude of the gene expression changes, with MVA/Ad eliciting greater transcriptional perturbation than Ad/MVA. Contrasting the two regimens revealed significant enrichment of epigenetic regulation pathways and augmented expression of MHC class I and II molecules associated with MVA/Ad. CONCLUSION: These data demonstrate that the order in which vaccines from heterologous prime-boost regimens are administered leads to distinct transcriptional responses and may shape the immune response induced by such combinations. The characterisation of early vaccine-induce responses strengthens our understanding of viral vector vaccine mechanisms of action ahead of their characterisation in human clinical trials and are a valuable resource to inform the pre-clinical design of appropriate vaccine constructs for emerging infectious diseases.


Assuntos
COVID-19 , Vacinas Virais , Adenoviridae/genética , Animais , Vacinas contra COVID-19 , Epigênese Genética , Vetores Genéticos/genética , Humanos , Imunização , Camundongos , SARS-CoV-2
9.
Viruses ; 13(10)2021 10 19.
Artigo em Inglês | MEDLINE | ID: mdl-34696536

RESUMO

The H1N1 pandemic of 2009-2010, MERS epidemic of 2012, Ebola epidemics of 2013-2016 and 2018-2020, Zika epidemic of 2015-2016, and COVID-19 pandemic of 2019-2021, are recent examples in the long history of epidemics that demonstrate the enormous global impact of viral infection. The rapid development of safe and effective vaccines and therapeutics has proven vital to reducing morbidity and mortality from newly emerging viruses. Structural biology methods can be used to determine how antibodies elicited during infection or vaccination target viral proteins and identify viral epitopes that correlate with potent neutralization. Here we review how structural and molecular biology approaches have contributed to our understanding of antibody recognition of pathogenic viruses, specifically HIV-1, SARS-CoV-2, and Zika. Determining structural correlates of neutralization of viruses has guided the design of vaccines, monoclonal antibodies, and small molecule inhibitors in response to the global threat of viral epidemics.


Assuntos
Anticorpos Neutralizantes/imunologia , Anticorpos Antivirais/imunologia , HIV-1/imunologia , SARS-CoV-2/imunologia , Zika virus/imunologia , Síndrome de Imunodeficiência Adquirida/imunologia , Síndrome de Imunodeficiência Adquirida/prevenção & controle , Anticorpos Monoclonais/imunologia , Anticorpos Monoclonais/uso terapêutico , COVID-19/imunologia , COVID-19/prevenção & controle , Cristalografia por Raios X , Humanos , Vacinas Virais/imunologia , Infecção por Zika virus/imunologia , Infecção por Zika virus/prevenção & controle
10.
Cell Rep ; 37(5): 109929, 2021 11 02.
Artigo em Inglês | MEDLINE | ID: mdl-34710354

RESUMO

Current coronavirus (CoV) vaccines primarily target immunodominant epitopes in the S1 subunit, which are poorly conserved and susceptible to escape mutations, thus threatening vaccine efficacy. Here, we use structure-guided protein engineering to remove the S1 subunit from the Middle East respiratory syndrome (MERS)-CoV spike (S) glycoprotein and develop stabilized stem (SS) antigens. Vaccination with MERS SS elicits cross-reactive ß-CoV antibody responses and protects mice against lethal MERS-CoV challenge. High-throughput screening of antibody-secreting cells from MERS SS-immunized mice led to the discovery of a panel of cross-reactive monoclonal antibodies. Among them, antibody IgG22 binds with high affinity to both MERS-CoV and severe acute respiratory syndrome (SARS)-CoV-2 S proteins, and a combination of electron microscopy and crystal structures localizes the epitope to a conserved coiled-coil region in the S2 subunit. Passive transfer of IgG22 protects mice against both MERS-CoV and SARS-CoV-2 challenge. Collectively, these results provide a proof of principle for cross-reactive CoV antibodies and inform the development of pan-CoV vaccines and therapeutic antibodies.


Assuntos
Anticorpos Antivirais/imunologia , Coronavírus da Síndrome Respiratória do Oriente Médio/imunologia , Glicoproteína da Espícula de Coronavírus/imunologia , Animais , Linhagem Celular , Infecções por Coronavirus/imunologia , Infecções por Coronavirus/prevenção & controle , Reações Cruzadas , Desenho de Fármacos , Mapeamento de Epitopos , Feminino , Imunoglobulina G/imunologia , Masculino , Camundongos , Camundongos Endogâmicos BALB C , SARS-CoV-2/imunologia , Glicoproteína da Espícula de Coronavírus/química , Vacinas Virais/imunologia
11.
Epidemiol Prev ; 45(4): 230-236, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34549564
15.
N Engl J Med ; 385(12): e35, 2021 09 16.
Artigo em Inglês | MEDLINE | ID: mdl-34525286

RESUMO

BACKGROUND: Although Zika virus (ZIKV) infection is typically self-limiting, other associated complications such as congenital birth defects and the Guillain-Barré syndrome are well described. There are no approved vaccines against ZIKV infection. METHODS: In this phase 1, open-label clinical trial, we evaluated the safety and immunogenicity of a synthetic, consensus DNA vaccine (GLS-5700) encoding the ZIKV premembrane and envelope proteins in two groups of 20 participants each. The participants received either 1 mg or 2 mg of vaccine intradermally, with each injection followed by electroporation (the use of a pulsed electric field to introduce the DNA sequence into cells) at baseline, 4 weeks, and 12 weeks. RESULTS: The median age of the participants was 38 years, and 60% were women; 78% were White and 22% Black; in addition, 30% were Hispanic. At the interim analysis at 14 weeks (i.e., after the third dose of vaccine), no serious adverse events were reported. Local reactions at the vaccination site (e.g., injection-site pain, redness, swelling, and itching) occurred in approximately 50% of the participants. After the third dose of vaccine, binding antibodies (as measured on enzyme-linked immunosorbent assay) were detected in all the participants, with geometric mean titers of 1642 and 2871 in recipients of 1 mg and 2 mg of vaccine, respectively. Neutralizing antibodies developed in 62% of the samples on Vero-cell assay. On neuronal-cell assay, there was 90% inhibition of ZIKV infection in 70% of the serum samples and 50% inhibition in 95% of the samples. The intraperitoneal injection of postvaccination serum protected 103 of 112 IFNAR knockout mice (bred with deletion of genes encoding interferon-α and interferon-ß receptors) (92%) that were challenged with a lethal dose of ZIKV-PR209 strain; none of the mice receiving baseline serum survived the challenge. Survival was independent of the neutralization titer. CONCLUSIONS: In this phase 1, open-label clinical trial, a DNA vaccine elicited anti-ZIKV immune responses. Further studies are needed to better evaluate the safety and efficacy of the vaccine. (Funded by GeneOne Life Science and others; ZIKA-001 ClinicalTrials.gov number, NCT02809443.).


Assuntos
Anticorpos Neutralizantes/sangue , Imunogenicidade da Vacina , Vacinas de DNA , Vacinas Virais/imunologia , Infecção por Zika virus/prevenção & controle , Zika virus/imunologia , Adulto , Animais , Anticorpos Antivirais/sangue , Feminino , Humanos , Injeções Intradérmicas/efeitos adversos , Masculino , Camundongos , Camundongos Knockout , Pessoa de Meia-Idade , Linfócitos T/fisiologia , Vacinas de DNA/administração & dosagem , Vacinas de DNA/efeitos adversos , Vacinas de DNA/imunologia , Infecção por Zika virus/imunologia
16.
J Vet Med Sci ; 83(11): 1686-1693, 2021 Oct 31.
Artigo em Inglês | MEDLINE | ID: mdl-34526420

RESUMO

Infectious bursal disease (IBD) causes severe economic damage to the poultry industry worldwide. To prevent IBD virus (IBDV) infection, live virus vaccines have been widely used in chickens having wide-ranging levels of maternally derived antibodies. But, the risks of infection with other pathogens because of lesions related to atrophy of the bursa of Fabricius in vaccinated chickens are a concern. To resolve the problems, a recombinant turkey herpesvirus (HVT) vaccine expressing IBDV-VP2 protein (rHVT-IBD) has been developed. However, the induction of neutralizing antibodies by rHVT-IBD against a virulent IBDV might be delayed compared with that by the live IBD vaccine, leading to the high risks of IBDV infection for young chickens. To find the best selection of IBDV vaccine for the onset of immunity, we examine the protective efficacy of a novel in ovo-attenuated live IBDV (IBD-CA) vaccine and the rHVT-IBD vaccine in young chickens challenged with a very virulent IBDV (vvIBDV) strain. We show that the protective efficacy of IBD-CA vaccine was higher than that of the rHVT-IBD vaccine in 14-day-old chickens challenged with the vvIBDV strain, leading to the risk of IBDV infection for young chickens when vaccinated with rHVT-IBD. Our results suggest that farmers should select the best vaccines to maximize vaccine efficacy in consideration of the vaccine characteristics, prevalence levels of IBDV in the areas, and initial MDA levels of the chickens since the attenuated live and recombinant vaccines play a role in the different vaccine efficacies.


Assuntos
Infecções por Birnaviridae , Vírus da Doença Infecciosa da Bursa , Doenças das Aves Domésticas , Vacinas Virais , Animais , Anticorpos Antivirais , Infecções por Birnaviridae/prevenção & controle , Infecções por Birnaviridae/veterinária , Bolsa de Fabricius , Galinhas , Doenças das Aves Domésticas/prevenção & controle , Vacinação/veterinária , Vacinas Sintéticas
17.
Nat Immunol ; 22(10): 1294-1305, 2021 10.
Artigo em Inglês | MEDLINE | ID: mdl-34556879

RESUMO

Development of effective human immunodeficiency virus 1 (HIV-1) vaccines requires synergy between innate and adaptive immune cells. Here we show that induction of the transcription factor CREB1 and its target genes by the recombinant canarypox vector ALVAC + Alum augments immunogenicity in non-human primates (NHPs) and predicts reduced HIV-1 acquisition in the RV144 trial. These target genes include those encoding cytokines/chemokines associated with heightened protection from simian immunodeficiency virus challenge in NHPs. Expression of CREB1 target genes probably results from direct cGAMP (STING agonist)-modulated p-CREB1 activity that drives the recruitment of CD4+ T cells and B cells to the site of antigen presentation. Importantly, unlike NHPs immunized with ALVAC + Alum, those immunized with ALVAC + MF59, the regimen in the HVTN702 trial that showed no protection from HIV infection, exhibited significantly reduced CREB1 target gene expression. Our integrated systems biology approach has validated CREB1 as a critical driver of vaccine efficacy and highlights that adjuvants that trigger CREB1 signaling may be critical for efficacious HIV-1 vaccines.


Assuntos
Proteína de Ligação ao Elemento de Resposta ao AMP Cíclico/imunologia , Infecções por HIV/imunologia , HIV-1/imunologia , Imunogenicidade da Vacina/imunologia , Vacinas Virais/imunologia , Vacinas contra a AIDS/imunologia , Adjuvantes Imunológicos/farmacologia , Animais , Linfócitos B/imunologia , Linfócitos T CD4-Positivos/imunologia , Expressão Gênica/imunologia , Vetores Genéticos/imunologia , Anticorpos Anti-HIV/imunologia , Infecções por HIV/virologia , Humanos , Imunização/métodos , Primatas/imunologia , Primatas/virologia , Vacinação/métodos
18.
Vaccine ; 39(41): 6174-6181, 2021 10 01.
Artigo em Inglês | MEDLINE | ID: mdl-34521550

RESUMO

Vaccinia virus has been used as a smallpox vaccine. Now that smallpox has been eradicated, the vaccinia virus is expected to be used as a bioterrorism countermeasure and a recombinant vaccine vector for other infectious diseases, such as viral hemorrhagic fevers. Many vaccinia virus strains were used as smallpox vaccines in the smallpox eradication campaign coordinated by the World Health Organization. These strains can be classified into generations, according to the history of improving production methods and efforts to reduce the adverse reactions. Significantly, the third-generation of smallpox vaccine strains, which include modified vaccinia Ankara (MVA) and LC16m8, are currently popular as recombinant vaccine vectors due to their well-balanced safety and immunogenicity profiles. The present review firstly focuses on the characteristics of the smallpox vaccine generations. The historical background of the development of the third-generation smallpox vaccine strains is detailed, along with the history of the transition of the vaccinia virus generation used as vectors for hemorrhagic fever vaccines to the third generation. Among the vaccinia viruses, MVA is currently the most commonly used vector for developing hemorrhagic fever vaccines, including dengue fever, yellow fever, Ebola viral disease, Lassa fever, Rift Valley fever, and Crimean-Congo hemorrhagic fever. LC16m8 is a vaccine candidate for severe fever with thrombocytopenia syndrome. The current status and recent advances in the development of these hemorrhagic fever vaccines using third-generation vaccinia strains are discussed.


Assuntos
Febres Hemorrágicas Virais , Vacina Antivariólica , Varíola , Vacinas Virais , Animais , Varíola/prevenção & controle , Vacinas Sintéticas/genética , Vírus Vaccinia/genética , Vacinas Virais/genética
19.
Front Immunol ; 12: 667889, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34512622

RESUMO

Type 1 diabetes (T1D) is the most common paediatric endocrine disease, and its frequency has been found to increase worldwide. Similar to all conditions associated with poorly regulated glucose metabolism, T1D carries an increased risk of infection. Consequently, careful compliance by T1D children with schedules officially approved for child immunization is strongly recommended. However, because patients with T1D show persistent and profound limitations in immune function, vaccines may evoke a less efficient immune response, with corresponding lower protection. Moreover, T1D is an autoimmune condition that develops in genetically susceptible individuals and some data regarding T1D triggering factors appear to indicate that infections, mainly those due to viruses, play a major role. Accordingly, the use of viral live attenuated vaccines is being debated. In this narrative review, we discussed the most effective and safe use of vaccines in patients at risk of or with overt T1D. Literature analysis showed that several problems related to the use of vaccines in children with T1D have not been completely resolved. There are few studies regarding the immunogenicity and efficacy of vaccines in T1D children, and the need for different immunization schedules has not been precisely established. Fortunately, the previous presumed relationship between vaccine administration and T1D appears to have been debunked, though some doubts regarding rotavirus vaccines remain. Further studies are needed to completely resolve the problems related to vaccine administration in T1D patients. In the meantime, the use of vaccines remains extensively recommended in children with this disease.


Assuntos
Diabetes Mellitus Tipo 1/imunologia , Vacinação , Vacinas Virais/administração & dosagem , Viroses/prevenção & controle , Diabetes Mellitus Tipo 1/epidemiologia , Humanos , Hospedeiro Imunocomprometido , Imunogenicidade da Vacina , Medição de Risco , Fatores de Risco , Vacinação/efeitos adversos , Vacinas Atenuadas/administração & dosagem , Vacinas Atenuadas/efeitos adversos , Vacinas Virais/efeitos adversos , Viroses/epidemiologia , Viroses/imunologia , Viroses/virologia
20.
Schweiz Arch Tierheilkd ; 163(9): 545-552, 2021 Sep.
Artigo em Alemão | MEDLINE | ID: mdl-34465558

RESUMO

INTRODUCTION: The aim of the vigilance system in Switzerland is the evaluation and classification of reported suspected adverse reactions of immunological veterinary medicines (IVMP), including suspected lack of expected efficacy. The Institute of Virology and Immunology (IVI) is the competent authority for marketing authorizations of immunological veterinary medicinal products in Switzerland and responsible for the vaccinovigilance system. In 2020, 130 adverse reaction reports were received (5% less compared to 2019). The reports mainly concerned dogs (41%) and cats (25%) followed by cattle (18%) and horses (7%). Many of the reports in dogs involved the application of combined vaccines against canine distemper, hepatitis, parvovirosis and parainfluenza in combination with canine leptospira components, in cats against cat flu and feline panleukopenia in combination with feline leukaemia virus infection. Causality assessments were done according to the international ABON system. In 27% of the reported cases, the causality assessments between the vaccination and the reaction described were evaluated as being probable (ABON A), in 44% as possible (ABON B).


Assuntos
Vacinas , Drogas Veterinárias , Vacinas Virais , Animais , Bovinos , Cães , Cavalos , Suíça , Vacinação/efeitos adversos , Vacinação/veterinária , Vacinas/efeitos adversos , Vacinas Combinadas , Drogas Veterinárias/efeitos adversos , Vacinas Virais/efeitos adversos
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