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1.
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
2.
mBio ; 12(2)2021 03 02.
Artigo em Inglês | MEDLINE | ID: mdl-33653888

RESUMO

There are no approved vaccines against the life-threatening Middle East respiratory syndrome coronavirus (MERS-CoV). Attenuated vaccines have proven their potential to induce strong and long-lasting immune responses. We have previously described that severe acute respiratory syndrome coronavirus (SARS-CoV) envelope (E) protein is a virulence factor. Based on this knowledge, a collection of mutants carrying partial deletions spanning the C-terminal domain of the E protein (rMERS-CoV-E*) has been generated using a reverse genetics system. One of these mutants, MERS-CoV-E*Δ2in, was attenuated and provided full protection in a challenge with virulent MERS-CoV after a single immunization dose. The MERS-CoV-E*Δ2in mutant was stable as it maintained its attenuation after 16 passages in cell cultures and has been selected as a promising vaccine candidate.IMPORTANCE The emergence of the new highly pathogenic human coronavirus SARS-CoV-2 that has already infected more than 80 million persons, killing nearly two million of them, clearly indicates the need to design efficient and safe vaccines protecting from these coronaviruses. Modern vaccines can be derived from virus-host interaction research directed to the identification of signaling pathways essential for virus replication and for virus-induced pathogenesis, in order to learn how to attenuate these viruses and design vaccines. Using a reverse genetics system developed in our laboratory, an infectious cDNA clone of MERS-CoV was engineered. Using this cDNA, we sequentially deleted several predicted and conserved motifs within the envelope (E) protein of MERS-CoV, previously associated with the presence of virulence factors. The in vitro and in vivo evaluation of these deletion mutants highlighted the relevance of predicted linear motifs in viral pathogenesis. Two of them, an Atg8 protein binding motif (Atg8-BM), and a forkhead-associated binding motif (FHA-BM), when deleted, rendered an attenuated virus that was evaluated as a vaccine candidate, leading to full protection against challenge with a lethal dose of MERS-CoV. This approach can be extended to the engineering of vaccines protecting against the new pandemic SARS-CoV-2.


Assuntos
Coronavírus da Síndrome Respiratória do Oriente Médio/patogenicidade , /imunologia , Engenharia Genética/métodos , Humanos , Coronavírus da Síndrome Respiratória do Oriente Médio/imunologia , Vacinas Atenuadas/uso terapêutico , Vacinas Virais/uso terapêutico
3.
J Exp Med ; 218(4)2021 04 05.
Artigo em Inglês | MEDLINE | ID: mdl-33544838

RESUMO

Yellow fever virus (YFV) live attenuated vaccine can, in rare cases, cause life-threatening disease, typically in patients with no previous history of severe viral illness. Autosomal recessive (AR) complete IFNAR1 deficiency was reported in one 12-yr-old patient. Here, we studied seven other previously healthy patients aged 13 to 80 yr with unexplained life-threatening YFV vaccine-associated disease. One 13-yr-old patient had AR complete IFNAR2 deficiency. Three other patients vaccinated at the ages of 47, 57, and 64 yr had high titers of circulating auto-Abs against at least 14 of the 17 individual type I IFNs. These antibodies were recently shown to underlie at least 10% of cases of life-threatening COVID-19 pneumonia. The auto-Abs were neutralizing in vitro, blocking the protective effect of IFN-α2 against YFV vaccine strains. AR IFNAR1 or IFNAR2 deficiency and neutralizing auto-Abs against type I IFNs thus accounted for more than half the cases of life-threatening YFV vaccine-associated disease studied here. Previously healthy subjects could be tested for both predispositions before anti-YFV vaccination.


Assuntos
Anticorpos Neutralizantes/imunologia , Autoanticorpos/imunologia , Doenças Autoimunes , Doenças Genéticas Inatas , Interferon-alfa , Receptor de Interferon alfa e beta , Vacina contra Febre Amarela , Vírus da Febre Amarela , Adolescente , Adulto , Idoso , Doenças Autoimunes/genética , Doenças Autoimunes/imunologia , /imunologia , Feminino , Doenças Genéticas Inatas/genética , Doenças Genéticas Inatas/imunologia , Células HEK293 , Humanos , Interferon-alfa/genética , Interferon-alfa/imunologia , Masculino , Pessoa de Meia-Idade , Receptor de Interferon alfa e beta/deficiência , Receptor de Interferon alfa e beta/imunologia , /imunologia , Vacinas Atenuadas/genética , Vacinas Atenuadas/imunologia , Vacina contra Febre Amarela/efeitos adversos , Vacina contra Febre Amarela/genética , Vacina contra Febre Amarela/imunologia , Vírus da Febre Amarela/genética , Vírus da Febre Amarela/imunologia
4.
Viruses ; 13(2)2021 02 08.
Artigo em Inglês | MEDLINE | ID: mdl-33567491

RESUMO

African swine fever (ASF), caused by the African swine fever virus (ASFV), is a major epidemic disease endangering the swine industry. Although a number of vaccine candidates have been reported, none are commercially available yet. To explore the effect of unknown genes on the biological characteristics of ASFV and the possibility of a gene-deleted isolate as a vaccine candidate, the strain SY18ΔL7-11, with deletions of L7L-L11L genes from ASFV SY18, was constructed, and its biological properties were analyzed. The results show that deletion of genes L7L-L11L did not affect replication of the virus in vitro. Virulence of SY18△L7-11 was significantly reduced, as 11 of the 12 pigs survived for 28 days after intramuscular inoculation with a low dose (103 TCID50) or a high dose (106 TCID50) of SY18ΔL7-11. All 11 surviving pigs were completely protected against challenge with the parental ASFV SY18 on 28 days postinoculation (dpi). Transient fever and/or irregularly low levels of genomic DNA in the blood were monitored in some pigs after inoculation. No ASF clinical signs or viremia were monitored after challenge. Antibodies to ASFV were induced in all pigs from 14 to 21 days postinoculation. IFN-γ was detected in most of the inoculated pigs, which is usually inhibited in ASFV-infected pigs. Overall, the results demonstrate that SY18ΔL7-11 is a candidate for further constructing safer vaccine(s), with better joint deletions of other gene(s) related to virulence.


Assuntos
Vírus da Febre Suína Africana/imunologia , Febre Suína Africana/prevenção & controle , Genes Virais/genética , Vacinas Virais/genética , Vírus da Febre Suína Africana/genética , Vírus da Febre Suína Africana/patogenicidade , Animais , Anticorpos Antivirais/sangue , Células Cultivadas , Deleção de Genes , Injeções Intramusculares , Interferon gama/sangue , Macrófagos/virologia , Suínos , Vacinas Atenuadas/administração & dosagem , Vacinas Atenuadas/genética , Vacinas Virais/administração & dosagem , Virulência/genética
5.
Nat Commun ; 12(1): 1102, 2021 02 17.
Artigo em Inglês | MEDLINE | ID: mdl-33597521

RESUMO

The four-dengue virus (DENV) serotypes infect several hundred million people annually. For the greatest safety and efficacy, tetravalent DENV vaccines are designed to stimulate balanced protective immunity to all four serotypes. However, this has been difficult to achieve. Clinical trials with a leading vaccine demonstrated that unbalanced replication and immunodominance of one vaccine component over others can lead to low efficacy and vaccine enhanced severe disease. The Laboratory of Infectious Diseases at the National Institutes of Health has developed a live attenuated tetravalent DENV vaccine (TV003), which is currently being tested in phase 3 clinical trials. Here we report, our study to determine if TV003 stimulate balanced and serotype-specific (TS) neutralizing antibody (nAb) responses to each serotype. Serum samples from twenty-one dengue-naive individuals participated under study protocol CIR287 (ClinicalTrials.gov NCT02021968) are analyzed 6 months after vaccination. Most subjects (76%) develop TS nAbs to 3 or 4 DENV serotypes, indicating immunity is induced by each vaccine component. Vaccine-induced TS nAbs map to epitopes known to be targets of nAbs in people infected with wild type DENVs. Following challenge with a partially attenuated strain of DENV2, all 21 subjects are protected from the efficacy endpoints. However, some vaccinated individuals develop post challenge nAb boost, while others mount post-challenge antibody responses that are consistent with sterilizing immunity. TV003 vaccine induced DENV2 TS nAbs are associated with sterilizing immunity. Our results indicate that nAbs to TS epitopes on each serotype may be a better correlate than total levels of nAbs currently used for guiding DENV vaccine development.


Assuntos
Anticorpos Neutralizantes/imunologia , Anticorpos Antivirais/imunologia , Vacinas contra Dengue/imunologia , Vírus da Dengue/imunologia , Dengue/imunologia , Formação de Anticorpos/imunologia , Especificidade de Anticorpos/imunologia , Dengue/prevenção & controle , Dengue/virologia , Vacinas contra Dengue/administração & dosagem , Vírus da Dengue/classificação , Epitopos/imunologia , Humanos , Sorotipagem , Especificidade da Espécie , Resultado do Tratamento , Vacinação/métodos , Vacinas Atenuadas/administração & dosagem , Vacinas Atenuadas/imunologia
6.
Artigo em Inglês | MEDLINE | ID: mdl-33573534

RESUMO

Abstract: This report, from the Australian Rotavirus Surveillance Program and collaborating laboratories Australia-wide, describes the rotavirus genotypes identified in children and adults with acute gastroenteritis during the period 1 January to 31 December 2018. During this period, 690 faecal specimens were referred for rotavirus G- and P- genotype analysis, including 607 samples that were confirmed as rotavirus positive. Of these, 457/607 were wild-type rotavirus strains and 150/607 were identified as rotavirus vaccine-like. Genotype analysis of the 457 wild-type rotavirus samples from both children and adults demonstrated that G3P[8] was the dominant genotype nationally, identified in 52% of samples, followed by G2P[4] (17%). The Australian National Immunisation Program, which previously included both RotaTeq and Rotarix vaccines, changed to Rotarix exclusively on 1 July 2017. Continuous surveillance is needed to identify if the change in vaccination schedule could affect rotavirus genotype distribution and diversity in Australia.


Assuntos
Infecções por Rotavirus/epidemiologia , Infecções por Rotavirus/prevenção & controle , Vacinas contra Rotavirus/imunologia , Austrália/epidemiologia , Pré-Escolar , Monitoramento Epidemiológico , Fezes/virologia , Feminino , Gastroenterite/epidemiologia , Gastroenterite/virologia , Genótipo , Humanos , Programas de Imunização , Lactente , Recém-Nascido , Masculino , Vigilância da População , Rotavirus/genética , Rotavirus/imunologia , Infecções por Rotavirus/virologia , Vacinas contra Rotavirus/administração & dosagem , Vacinas Atenuadas
7.
Artigo em Inglês | MEDLINE | ID: mdl-33573535

RESUMO

Abstract: This report, from the Australian Rotavirus Surveillance Program and collaborating laboratories Australia-wide, describes the rotavirus genotypes identified in children and adults with acute gastroenteritis during the period 1 January to 31 December 2019. During this period, 964 faecal specimens had been referred for rotavirus G- and P- genotype analysis, including 894 samples that were confirmed as rotavirus positive. Of these, 724/894 were wild-type rotavirus strains and 169/894 were identified as vaccine-like. A single sample could not be determined as wild-type or vaccine-like due to poor sequencing. Genotype analysis of the 724 wild-type rotavirus samples from both children and adults demonstrated that G3P[8] was the dominant genotype nationally, identified in 46.7% of samples, followed by G2P[4] in 8.8% of samples. The Australian National Immunisation Program (NIP) changed to the exclusive use of Rotarix as of 1 July 2017. The NIP had previously included two live-attenuated oral vaccines: Rotarix (monovalent, human) and RotaTeq (pentavalent, human-bovine reassortant) in a state-based vaccine selection. Continuous surveillance is imperative to determine the effect of this change in rotavirus vaccine schedule on the genotype distribution and diversity in Australia.


Assuntos
Programas de Imunização/estatística & dados numéricos , Infecções por Rotavirus/epidemiologia , Infecções por Rotavirus/prevenção & controle , Animais , Austrália/epidemiologia , Bovinos , Pré-Escolar , Monitoramento Epidemiológico , Fezes/virologia , Feminino , Gastroenterite/epidemiologia , Gastroenterite/prevenção & controle , Gastroenterite/virologia , Humanos , Lactente , Recém-Nascido , Masculino , Vigilância da População , Rotavirus/genética , Rotavirus/isolamento & purificação , Infecções por Rotavirus/virologia , Vacinas contra Rotavirus/administração & dosagem , Vacinas contra Rotavirus/imunologia , Vacinas Atenuadas
8.
mBio ; 12(1)2021 01 05.
Artigo em Inglês | MEDLINE | ID: mdl-33402534

RESUMO

The development of safe and effective vaccines against viruses is central to disease control. With advancements in DNA synthesis technology, the production of synthetic viral genomes has fueled many research efforts that aim to generate attenuated viruses by introducing synonymous mutations. Elucidation of the mechanisms underlying virus attenuation through synonymous mutagenesis is revealing interesting new biology that can be exploited for vaccine development. Here, we review recent advancements in this field of synthetic virology and focus on the molecular mechanisms of attenuation by genetic recoding of viruses. We highlight the action of the zinc finger antiviral protein (ZAP) and RNase L, two proteins involved in the inhibition of viruses enriched for CpG and UpA dinucleotides, that are often the products of virus recoding algorithms. Additionally, we discuss current challenges in the field as well as studies that may illuminate how other host functions, such as translation, are potentially involved in the attenuation of recoded viruses.


Assuntos
Genoma Viral , Vacinas Atenuadas/genética , Vacinas Virais/genética , Vírus/genética , Animais , Vírus de DNA , Fosfatos de Dinucleosídeos , Endorribonucleases/genética , Humanos , Mutação Silenciosa , Replicação Viral
9.
Muscle Nerve ; 63(3): 294-303, 2021 03.
Artigo em Inglês | MEDLINE | ID: mdl-33471383

RESUMO

The clinical course of neuromuscular disorders (NMDs) can be affected by infections, both in immunocompetent individuals, and in those with reduced immunocompetence due to immunosuppressive/immunomodulating therapies. Infections and immunizations may also trigger NMDs. There is a potential for reduced efficacy of immunizations in patients with reduced immunocompetence. The recent vaccination program for coronavirus disease-2019 (COVID-19) raises several questions regarding the safety and efficacy of this vaccine in individuals with NMDs. In this Practice Topic article, we address the role of vaccine-preventable infections in NMDs and the safety and efficacy of immunization in individuals with NMDs, with emphasis on vaccination against COVID-19.


Assuntos
/uso terapêutico , Imunossupressores/efeitos adversos , Doenças Neuromusculares/terapia , Doenças Preveníveis por Vacina/prevenção & controle , /complicações , /imunologia , Síndrome de Guillain-Barré/epidemiologia , Síndrome de Guillain-Barré/etiologia , Humanos , Imunocompetência/imunologia , Hospedeiro Imunocomprometido/imunologia , Fatores Imunológicos/efeitos adversos , Doenças Neuromusculares/epidemiologia , Doenças Neuromusculares/imunologia , Vacinas Atenuadas/uso terapêutico , Vacinas de Produtos Inativados/uso terapêutico
10.
Res Vet Sci ; 134: 102-111, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-33360570

RESUMO

Modified live vaccines (MLVs) have been utilized to combat porcine reproductive and respiratory syndrome (PRRS), which raises a serious concern about the MLV-derived PRRS virus (PRRSV) isolates. During the routine investigation of PRRSV in China, four lung samples collected from unvaccinated diseased pigs from 2016 to 2020 were detected as PRRSV positive. The PRRSVs shared high ORF5 identities to CH-1R, JXA1-R, TJM-F92 and RespPRRS MLV vaccines, respectively. The viruses were isolated in Marc-145 cells and denominated as SD1612-1, JS1703-21, JSTZ1907-714 and JSYC20-05-1. Genome comparison confirmed that these isolates share the highest genomic homologies to CH-1R (97.96%), JXA1-R (99.64%), TJM-F92 (99.00%) and RespPRRS MLV (99.57%) than any other known isolates. Genome-based phylogenetic analysis showed that SD1612-1 and CH-1R, JS1703-21 and JXA1-R, JSTZ1907-714 and TJM-F92, JSYC20-05-1 and RespPRRS MLV were grouped in the same branches. In addition, amino acids unique to corresponding vaccine attenuations were also identified in our isolates. Noticeably, amino-acids potentially associated with the virulence revision from MLV strains to parental virulent viruses were also identified in the MLV-derived isolates. Our results confirm that the four types of MLV-derived isolates are circulating and evolving in Chinese swine herds for years, which highlights the necessity for the fair use of PRRS MLVs.


Assuntos
Síndrome Respiratória e Reprodutiva Suína/virologia , Vírus da Síndrome Respiratória e Reprodutiva Suína/isolamento & purificação , Doenças dos Suínos/virologia , Vacinas Atenuadas , Vacinas Virais , Animais , China , Genômica , Filogenia , Síndrome Respiratória e Reprodutiva Suína/prevenção & controle , Vírus da Síndrome Respiratória e Reprodutiva Suína/genética , Vírus da Síndrome Respiratória e Reprodutiva Suína/imunologia , Vírus da Síndrome Respiratória e Reprodutiva Suína/patogenicidade , Suínos , Doenças dos Suínos/prevenção & controle , Vacinas Atenuadas/genética , Vacinas Virais/administração & dosagem , Vacinas Virais/genética , Vacinas Virais/imunologia , Virulência
11.
Nat Rev Immunol ; 21(2): 83-100, 2021 02.
Artigo em Inglês | MEDLINE | ID: mdl-33353987

RESUMO

Immunization is a cornerstone of public health policy and is demonstrably highly cost-effective when used to protect child health. Although it could be argued that immunology has not thus far contributed much to vaccine development, in that most of the vaccines we use today were developed and tested empirically, it is clear that there are major challenges ahead to develop new vaccines for difficult-to-target pathogens, for which we urgently need a better understanding of protective immunity. Moreover, recognition of the huge potential and challenges for vaccines to control disease outbreaks and protect the older population, together with the availability of an array of new technologies, make it the perfect time for immunologists to be involved in designing the next generation of powerful immunogens. This Review provides an introductory overview of vaccines, immunization and related issues and thereby aims to inform a broad scientific audience about the underlying immunological concepts.


Assuntos
Controle de Doenças Transmissíveis/métodos , Doenças Transmissíveis/imunologia , Vacinas Atenuadas/imunologia , Vacinas de Produtos Inativados/imunologia , Vacinologia/métodos , Anticorpos/imunologia , Antígenos/imunologia , Humanos , Memória Imunológica/imunologia , Linfócitos T/imunologia , Vacinação
12.
Methods Mol Biol ; 2183: 331-356, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-32959252

RESUMO

Vaccination was developed by Edward Jenner in 1796. Since then, vaccination and vaccine development research has been a hotspot of research in the scientific community. Various ways of vaccine development are successfully employed in mass production of vaccines. One of the most successful ways to generate vaccines is the method of virulence attenuation in pathogens. The attenuated strains of viruses, bacteria, and parasites are used as vaccines which elicit robust immune response and confers protection against virulent pathogens. This chapter brings together the most common and efficient ways of generating live attenuated vaccine strains in viruses, bacteria, and parasites.


Assuntos
Vacinas Atenuadas/imunologia , Vacinologia/métodos , Animais , Vacinas Bacterianas , Linhagem Celular , Uso do Códon , Feminino , Raios gama , Inativação Gênica , Humanos , Imunização , Imunogenicidade da Vacina , Vírus da Influenza A , Camundongos , MicroRNAs/genética , Modelos Animais , Mutagênese , Infecções por Orthomyxoviridae/imunologia , Infecções por Orthomyxoviridae/prevenção & controle , Vacinas Protozoárias/genética , Vacinas Protozoárias/imunologia , Radiação Ionizante , Vacinas Atenuadas/genética , Virulência/imunologia
13.
PLoS Pathog ; 16(12): e1009096, 2020 12.
Artigo em Inglês | MEDLINE | ID: mdl-33315936

RESUMO

Bacille Calmette-Guerin (BCG), an attenuated whole cell vaccine based on Mycobacterium bovis, is the only licensed vaccine against Mycobacterium tuberculosis (Mtb), but its efficacy is suboptimal and it fails to protect against pulmonary tuberculosis. We previously reported that Mtb lacking the virulence genes lprG and rv1410c (ΔLprG) was highly attenuated in immune deficient mice. In this study, we show that attenuated ΔLprG Mtb protects C57BL/6J, Balb/cJ, and C3HeB/FeJ mice against Mtb challenge and is as attenuated as BCG in SCID mice. In C3HeB/FeJ mice, ΔLprG vaccination resulted in innate peripheral cytokine production and induced high polyclonal PPD-specific cytokine-secreting CD4+ T lymphocytes in peripheral blood. The ΔLprG vaccine afforded protective efficacy in the lungs of C3H/FeJ mice following both H37Rv and Erdman aerosolized Mtb challenges. Vaccine efficacy correlated with antigen-specific PD-1-negative CD4+ T lymphocytes as well as with serum IL-17 levels after vaccination. We hypothesize that induction of Th17 cells in lung is critical for vaccine protection, and we show a serum cytokine biomarker for IL-17 shortly after vaccination may predict protective efficacy.


Assuntos
Vacinas contra a Tuberculose/genética , Vacinas contra a Tuberculose/imunologia , Vacinas Atenuadas/genética , Vacinas Atenuadas/imunologia , Fatores de Virulência/genética , Animais , Genes Bacterianos/genética , Interleucina-17/imunologia , Camundongos , Mycobacterium tuberculosis/genética , Mycobacterium tuberculosis/imunologia , Células Th17/imunologia , Tuberculose Pulmonar/imunologia , Tuberculose Pulmonar/prevenção & controle
15.
Viruses ; 12(12)2020 12 21.
Artigo em Inglês | MEDLINE | ID: mdl-33371460

RESUMO

African swine fever (ASF) has become the major threat for the global swine industry. Furthermore, the epidemiological situation of African swine fever virus (ASFV) in some endemic regions of Sub-Saharan Africa is worse than ever, with multiple virus strains and genotypes currently circulating in a given area. Despite the recent advances on ASF vaccine development, there are no commercial vaccines yet, and most of the promising vaccine prototypes available today have been specifically designed to fight the genotype II strains currently circulating in Europe, Asia, and Oceania. Previous results from our laboratory have demonstrated the ability of BA71∆CD2, a recombinant LAV lacking CD2v, to confer protection against homologous (BA71) and heterologous genotype I (E75) and genotype II (Georgia2007/01) ASFV strains, both belonging to same clade (clade C). Here, we extend these results using BA71∆CD2 as a tool trying to understand ASFV cross-protection, using phylogenetically distant ASFV strains. We first observed that five out of six (83.3%) of the pigs immunized once with 106 PFU of BA71∆CD2 survived the tick-bite challenge using Ornithodoros sp. soft ticks naturally infected with RSA/11/2017 strain (genotype XIX, clade D). Second, only two out of six (33.3%) survived the challenge with Ken06.Bus (genotype IX, clade A), which is phylogenetically more distant to BA71∆CD2 than the RSA/11/2017 strain. On the other hand, homologous prime-boosting with BA71∆CD2 only improved the survival rate to 50% after Ken06.Bus challenge, all suffering mild ASF-compatible clinical signs, while 100% of the pigs immunized with BA71∆CD2 and boosted with the parental BA71 virulent strain survived the lethal challenge with Ken06.Bus, without almost no clinical signs of the disease. Our results confirm that cross-protection is a multifactorial phenomenon that not only depends on sequence similarity. We believe that understanding this complex phenomenon will be useful for designing future vaccines for ASF-endemic areas.


Assuntos
Vírus da Febre Suína Africana/imunologia , Febre Suína Africana/imunologia , Febre Suína Africana/virologia , Proteção Cruzada/imunologia , Vacinas Atenuadas/imunologia , Vacinas Virais/imunologia , Febre Suína Africana/prevenção & controle , Vírus da Febre Suína Africana/genética , Animais , Anticorpos Antivirais/imunologia , Especificidade de Anticorpos/imunologia , Células COS , Linhagem Celular , Chlorocebus aethiops , Genótipo , Imunização , Imunoglobulina G/imunologia , Suínos , Proteínas Virais/imunologia
16.
N Engl J Med ; 383(20): 1932-1940, 2020 11 12.
Artigo em Inglês | MEDLINE | ID: mdl-33176083

RESUMO

BACKGROUND: A three-dose, oral rotavirus vaccine (Rotavac) was introduced in the universal immunization program in India in 2016. A prelicensure trial involving 6799 infants was not large enough to detect a small increased risk of intussusception. Postmarketing surveillance data would be useful in assessing whether the risk of intussusception would be similar to the risk seen with different rotavirus vaccines used in other countries. METHODS: We conducted a multicenter, hospital-based, active surveillance study at 27 hospitals in India. Infants meeting the Brighton level 1 criteria of radiologic or surgical confirmation of intussusception were enrolled, and rotavirus vaccination was ascertained by means of vaccination records. The relative incidence (incidence during the risk window vs. all other times) of intussusception among infants 28 to 365 days of age within risk windows of 1 to 7 days, 8 to 21 days, and 1 to 21 days after vaccination was evaluated by means of a self-controlled case-series analysis. For a subgroup of patients, a matched case-control analysis was performed, with matching for age, sex, and location. RESULTS: From April 2016 through June 2019, a total of 970 infants with intussusception were enrolled, and 589 infants who were 28 to 365 days of age were included in the self-controlled case-series analysis. The relative incidence of intussusception after the first dose was 0.83 (95% confidence interval [CI], 0.00 to 3.00) in the 1-to-7-day risk window and 0.35 (95% CI, 0.00 to 1.09) in the 8-to-21-day risk window. Similar results were observed after the second dose (relative incidence, 0.86 [95% CI, 0.20 to 2.15] and 1.23 [95% CI, 0.60 to 2.10] in the respective risk windows) and after the third dose (relative incidence, 1.65 [95% CI, 0.82 to 2.64] and 1.08 [95% CI, 0.69 to 1.73], respectively). No increase in intussusception risk was found in the case-control analysis. CONCLUSIONS: The rotavirus vaccine produced in India that we evaluated was not associated with intussusception in Indian infants. (Funded by the Bill and Melinda Gates Foundation and others.).


Assuntos
Intussuscepção/etiologia , Vacinas contra Rotavirus/efeitos adversos , Administração Oral , Estudos de Casos e Controles , Feminino , Humanos , Imunização Secundária/efeitos adversos , Incidência , Índia/epidemiologia , Lactente , Intussuscepção/epidemiologia , Masculino , Vigilância de Produtos Comercializados , Risco , Infecções por Rotavirus/prevenção & controle , Vacinação , Vacinas Atenuadas/efeitos adversos
17.
Front Immunol ; 11: 2130, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33013898

RESUMO

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


Assuntos
Betacoronavirus/imunologia , Doenças Transmissíveis Emergentes/prevenção & controle , Doenças Transmissíveis Emergentes/virologia , Infecções por Coronavirus/prevenção & controle , Pandemias/prevenção & controle , Pneumonia Viral/prevenção & controle , Vacinação , Vacinas Virais/imunologia , Animais , Anticorpos Facilitadores/imunologia , Infecções por Coronavirus/imunologia , Infecções por Coronavirus/terapia , Infecções por Coronavirus/virologia , Reações Cruzadas/imunologia , Humanos , Imunização Passiva , Pneumonia Viral/terapia , Pneumonia Viral/virologia , Vacinas Atenuadas/imunologia , Vacinas de DNA/imunologia , Vacinas de Produtos Inativados/imunologia , Vacinas de Subunidades/imunologia
18.
Biomolecules ; 10(10)2020 10 14.
Artigo em Inglês | MEDLINE | ID: mdl-33066343

RESUMO

Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) is the causative agent of the coronavirus disease 2019 (COVID-19) pandemic spreading around the world, causing massive distress to the world's economy and affecting healthcare systems worldwide. Although some exposed individuals have no symptoms and most symptomatic infections are not severe, COVID-19 cases span a wide spectrum, ranging from mild to critical and sometimes resulting in life-threatening complications, such as pneumonia, severe respiratory distress and cardiac problems. Currently, there is no curative drug for COVID-19 and vaccines are still under development. We are presenting here a strategy for the fast development of natural live-attenuated SARS-CoV-2 vaccines. Our proposed approach is based on screening for, identifying, analyzing and selecting naturally attenuated yet highly immunogenic SARS-CoV-2 strains, which may lead to a shorter cycle of vaccine development, as well as higher vaccine effectiveness.


Assuntos
Infecções por Coronavirus/imunologia , Pneumonia Viral/imunologia , Vacinas Atenuadas/imunologia , Vacinas Virais/imunologia , Infecções por Coronavirus/prevenção & controle , Humanos , Pandemias/prevenção & controle , Pneumonia Viral/prevenção & controle , Vacinas Atenuadas/efeitos adversos , Vacinas Virais/efeitos adversos
19.
Signal Transduct Target Ther ; 5(1): 237, 2020 10 13.
Artigo em Inglês | MEDLINE | ID: mdl-33051445

RESUMO

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is an emerging virus that is highly pathogenic and has caused the recent worldwide pandemic officially named coronavirus disease (COVID-19). Currently, considerable efforts have been put into developing effective and safe drugs and vaccines against SARS-CoV-2. Vaccines, such as inactivated vaccines, nucleic acid-based vaccines, and vector vaccines, have already entered clinical trials. In this review, we provide an overview of the experimental and clinical data obtained from recent SARS-CoV-2 vaccines trials, and highlight certain potential safety issues that require consideration when developing vaccines. Furthermore, we summarize several strategies utilized in the development of vaccines against other infectious viruses, such as severe acute respiratory syndrome coronavirus (SARS-CoV) and Middle East respiratory syndrome coronavirus (MERS-CoV), with the aim of aiding in the design of effective therapeutic approaches against SARS-CoV-2.


Assuntos
Anticorpos Antivirais/biossíntese , Infecções por Coronavirus/prevenção & controle , Pandemias/prevenção & controle , Peptidil Dipeptidase A/genética , Pneumonia Viral/prevenção & controle , Receptores Virais/genética , Vacinas Virais/biossíntese , Betacoronavirus/efeitos dos fármacos , Betacoronavirus/imunologia , Betacoronavirus/patogenicidade , Ensaios Clínicos como Assunto , Infecções por Coronavirus/imunologia , Infecções por Coronavirus/virologia , Regulação da Expressão Gênica/efeitos dos fármacos , Humanos , Imunidade Inata/efeitos dos fármacos , Esquemas de Imunização , Imunogenicidade da Vacina , Coronavírus da Síndrome Respiratória do Oriente Médio/efeitos dos fármacos , Coronavírus da Síndrome Respiratória do Oriente Médio/imunologia , Coronavírus da Síndrome Respiratória do Oriente Médio/patogenicidade , Segurança do Paciente , Peptidil Dipeptidase A/metabolismo , Pneumonia Viral/imunologia , Pneumonia Viral/virologia , Ligação Proteica , Receptores Virais/antagonistas & inibidores , Receptores Virais/metabolismo , Vírus da SARS/efeitos dos fármacos , Vírus da SARS/imunologia , Vírus da SARS/patogenicidade , Síndrome Respiratória Aguda Grave/imunologia , Síndrome Respiratória Aguda Grave/prevenção & controle , Síndrome Respiratória Aguda Grave/virologia , 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 , Vacinas Virais/administração & dosagem
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