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1.
Sci Rep ; 11(1): 5804, 2021 03 11.
Artigo em Inglês | MEDLINE | ID: mdl-33707532

RESUMO

COVID-19 outbreak caused by SARS-CoV-2 created an unprecedented health crisis since there is no vaccine for this novel virus. Therefore, SARS-CoV-2 vaccines have become crucial for reducing morbidity and mortality. In this study, in vitro and in vivo safety and efficacy analyzes of lyophilized vaccine candidates inactivated by gamma-irradiation were performed. The candidate vaccines in this study were OZG-3861 version 1 (V1), an inactivated SARS-CoV-2 virus vaccine, and SK-01 version 1 (V1), a GM-CSF adjuvant added vaccine. The candidate vaccines were applied intradermally to BALB/c mice to assess toxicity and immunogenicity. Preliminary results in vaccinated mice are reported in this study. Especially, the vaccine models containing GM-CSF caused significant antibody production with neutralization capacity in absence of the antibody-dependent enhancement feature, when considered in terms of T and B cell responses. Another important finding was that the presence of adjuvant was more important in T cell in comparison with B cell response. Vaccinated mice showed T cell response upon restimulation with whole inactivated SARS-CoV-2 or peptide pool. This study shows that the vaccines are effective and leads us to start the challenge test to investigate the gamma-irradiated inactivated vaccine candidates for infective SARS-CoV-2 virus in humanized ACE2 + mice.


Assuntos
/imunologia , Imunogenicidade da Vacina , Vacinas de Produtos Inativados/imunologia , Animais , Feminino , Raios gama , Genoma Viral , Humanos , Masculino , Camundongos Endogâmicos BALB C , Vacinas de Produtos Inativados/toxicidade
2.
Radiat Res ; 195(3): 221-229, 2021 03 01.
Artigo em Inglês | MEDLINE | ID: mdl-33411888

RESUMO

Immunization with an inactivated virus is one of the strategies currently being tested towards developing a SARS-CoV-2 vaccine. One of the methods used to inactivate viruses is exposure to high doses of ionizing radiation to damage their nucleic acids. While gamma (γ) rays effectively induce lesions in the RNA, envelope proteins are also highly damaged in the process. This in turn may alter their antigenic properties, affecting their capacity to induce an adaptive immune response able to confer effective protection. Here, we modeled the effect of sparsely and densely ionizing radiation on SARS-CoV-2 using the Monte Carlo toolkit Geant4-DNA. With a realistic 3D target virus model, we calculated the expected number of lesions in the spike and membrane proteins, as well as in the viral RNA. Our findings showed that γ rays produced significant spike protein damage, but densely ionizing charged particles induced less membrane damage for the same level of RNA lesions, because a single ion traversal through the nuclear envelope was sufficient to inactivate the virus. We propose that accelerated charged particles produce inactivated viruses with little structural damage to envelope proteins, thereby representing a new and effective tool for developing vaccines against SARS-CoV-2 and other enveloped viruses.


Assuntos
/imunologia , Método de Monte Carlo , /efeitos da radiação , Humanos , Transferência Linear de Energia , RNA Viral/efeitos da radiação , Glicoproteína da Espícula de Coronavírus/efeitos da radiação , Vacinas de Produtos Inativados/imunologia
3.
JAMA Netw Open ; 4(1): e2031266, 2021 01 04.
Artigo em Inglês | MEDLINE | ID: mdl-33443580

RESUMO

Importance: Trivalent adjuvanted inactivated influenza vaccine (aIIV3) and trivalent high-dose inactivated influenza vaccine (HD-IIV3) are US-licensed for adults aged 65 years and older. Data are needed on the comparative safety, reactogenicity, and health-related quality of life (HRQOL) effects of these vaccines. Objective: To compare safety, reactogenicity, and changes in HRQOL scores after aIIV3 vs HD-IIV3. Design, Setting, and Participants: This randomized blinded clinical trial was a multicenter US study conducted during the 2017 to 2018 and 2018 to 2019 influenza seasons. Among 778 community-dwelling adults aged at least 65 years and assessed for eligibility, 13 were ineligible and 8 withdrew before randomization. Statistical analysis was performed from August 2019 to August 2020. Interventions: Intramuscular administration of aIIV3 or HD-IIV3 after age-stratification (65-79 years; ≥80 years) and randomization. Main Outcomes and Measures: Proportions of participants with moderate-to-severe injection-site pain and 14 other solicited reactions during days 1 to 8, using a noninferiority test (5% noninferiority margin), and serious adverse events (SAE) and adverse events of clinical interest (AECI), including new-onset immune-mediated conditions, during days 1 to 43. Changes in HRQOL scores before and after vaccination (days 1, 3) were also compared between study groups. Results: A total of 757 adults were randomized, 378 to receive aIIV3 and 379 to receive HD-IIV3. Of these participants, there were 420 women (55%) and 589 White individuals (78%) with a median (range) age of 72 (65-97) years. The proportion reporting moderate-to-severe injection-site pain, limiting or preventing activity, after aIIV3 (12 participants [3.2%]) (primary outcome) was noninferior compared with HD-IIV3 (22 participants [5.8%]) (difference -2.7%; 95% CI, -5.8 to 0.4). Ten reactions met noninferiority criteria for aIIV3; 4 (moderate-to-severe injection-site tenderness, arthralgia, fatigue, malaise) did not. It was inconclusive whether these 4 reactions occurred in higher proportions of participants after aIIV3. No participant sought medical care for a vaccine reaction. No AECI was observed. Nine participants had at least SAE after aIIV3 (2.4%; 95% CI,1.1% to 4.5%); 3 had at least 1 SAE after HD-IIV3 (0.8%; 95% CI, 0.2% to 2.2%). No SAE was associated with vaccination. Changes in prevaccination and postvaccination HRQOL scores were not clinically meaningful and not different between the groups. Conclusions and Relevance: Overall safety and HRQOL findings were similar after aIIV3 and HD-IIV3, and consistent with prelicensure data. From a safety standpoint, this study's results support using either vaccine to prevent influenza in older adults. Trial Registration: ClinicalTrials.gov Identifier: NCT03183908.


Assuntos
Adjuvantes Imunológicos , Vacinas contra Influenza , Influenza Humana/prevenção & controle , Qualidade de Vida , Vacinas de Produtos Inativados , Adjuvantes Imunológicos/administração & dosagem , Adjuvantes Imunológicos/efeitos adversos , Idoso , Idoso de 80 Anos ou mais , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/epidemiologia , Feminino , Humanos , Vacinas contra Influenza/administração & dosagem , Vacinas contra Influenza/efeitos adversos , Vacinas contra Influenza/imunologia , Injeções Intramusculares , Masculino , Vacinas de Produtos Inativados/administração & dosagem , Vacinas de Produtos Inativados/efeitos adversos , Vacinas de Produtos Inativados/imunologia
4.
Arch Virol ; 166(2): 571-579, 2021 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-33410993

RESUMO

This study compared concurrent and separate primary vaccination against equid alphaherpesviruses 1 and 4, genus Varicellovirus, subfamily Alphaherpesvirinae, family Herpesviridae, and equine influenza A virus, genus Alphainfluenzavirus, family Orthomyxoviridae. Their vernacular names are equine herpesvirus 1 and 4 (EHV1/4) and equine influenza virus (EIV). Infection with these respiratory pathogens is associated with loss of performance, interruption of training schedules, and on occasion, cancellation of equestrian events. Vaccination is highly recommended, and for some activities it is a mandatory requirement of the relevant authority. As there is a dearth of information relating to the impact of concurrent vaccination on the antibody response to EHV and EIV vaccines, they are usually administered separately, often 2 weeks apart. In a previous study of booster vaccination in Thoroughbred racehorses, concurrent vaccination with whole-virus inactivated carbopol-adjuvanted EHV and EIV vaccines did not impact negatively on the antibody response. In this study, investigations were extended to concurrent versus separate primary vaccination of warmblood foals. A field study was conducted to compare the immune response to a carbopol-adjuvanted EHV vaccine and an immune stimulating complex (ISCOM)-adjuvanted EI vaccine administered concurrently and 2 weeks apart. No adverse clinical reactions were observed, the pattern of EI and EHV antibody response was similar for both groups, and there was no evidence that concurrent primary vaccination compromised the humoral response. The results are of relevance to horse owners who wish to decrease veterinary costs, limit handling of young animals, and simplify record keeping by vaccinating concurrently.


Assuntos
Infecções por Herpesviridae/imunologia , Vacinas contra Herpesvirus/imunologia , Doenças dos Cavalos/imunologia , Cavalos/imunologia , Vírus da Influenza A/imunologia , Vacinas contra Influenza/imunologia , Adjuvantes Imunológicos/administração & dosagem , Animais , Anticorpos Antivirais/imunologia , Formação de Anticorpos/imunologia , Feminino , Doenças dos Cavalos/virologia , Cavalos/virologia , Imunidade Humoral/imunologia , Imunização Secundária/métodos , Infecções por Orthomyxoviridae/imunologia , Infecções por Orthomyxoviridae/virologia , Vacinação/métodos , Vacinas de Produtos Inativados/imunologia
5.
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
6.
Ann Pharmacother ; 55(1): 89-97, 2021 01.
Artigo em Inglês | MEDLINE | ID: mdl-32578447

RESUMO

OBJECTIVE: To review the efficacy and safety of the high-dose inactivated influenza vaccine quadrivalent (HD-IIV4) in the prevention of influenza in older adults. DATA SOURCES: A literature search was performed using PubMed and Google Scholar with the search terms high-dose, influenza vaccine, and quadrivalent. Other resources included the Centers for Disease Control and Prevention (CDC), the prescribing information, and the manufacturer's website. STUDY SELECTION AND DATA EXTRACTION: All relevant English-language articles of studies assessing the efficacy and safety of HD-IIV4 were included. DATA SYNTHESIS: HD-IIV4 is licensed by the Food and Drug Administration for the prevention of influenza in adults aged 65 years and older. The safety and immunogenicity of HD-IIV4 was demonstrated in a phase 3 trial, and the efficacy of the trivalent formulation (HD-IIV3) was demonstrated in a phase 3b-4 trial. HD-IIV4 carries a warning regarding the occurrence of Guillain-Barré syndrome. Adverse reactions, including injection-site pain and myalgia, were reported more frequently with HD-IIV4 than with HD-IIV3. RELEVANCE TO PATIENT CARE AND CLINICAL PRACTICE: Although the CDC recommends any age-appropriate influenza vaccine for adults aged 65 years and older, HD-IIV4 was associated with improved immunogenicity against the added B strain and HD-IIV3 provided better protection against influenza than the standard-dose vaccine. Other influenza vaccines have weaker evidence of efficacy in older adults. Therefore, HDIIV4 should be recommended as the vaccine of choice in adults aged 65 years and older. CONCLUSION: HD-IIV4 has proven immunogenic, safe, and effective in preventing influenza in older adults and should be recommended as the vaccine of choice in this patient population.


Assuntos
Vacinas contra Influenza/administração & dosagem , Influenza Humana/prevenção & controle , Idoso , Idoso de 80 Anos ou mais , Anticorpos Antivirais/imunologia , Ensaios Clínicos como Assunto , Feminino , Testes de Inibição da Hemaglutinação , Humanos , Imunogenicidade da Vacina/efeitos dos fármacos , Vacinas contra Influenza/efeitos adversos , Vacinas contra Influenza/imunologia , Influenza Humana/imunologia , Masculino , Dor/induzido quimicamente , Estados Unidos , United States Food and Drug Administration , Vacinas de Produtos Inativados/administração & dosagem , Vacinas de Produtos Inativados/efeitos adversos , Vacinas de Produtos Inativados/imunologia
7.
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
8.
Lancet ; 396(10261): 1491-1503, 2020 11 07.
Artigo em Inglês | MEDLINE | ID: mdl-33065035

RESUMO

BACKGROUND: Seasonal influenza remains a substantial public health threat despite the availability of egg-derived and other vaccines. Plant-based manufacturing might address some of the limitations of current vaccines. We describe two phase 3 efficacy studies of a recombinant quadrivalent virus-like particle (QVLP) influenza vaccine manufactured in plants, one in adults aged 18-64 years (the 18-64 study) and one in older people aged 65 years and older (the 65-plus study). METHODS: We did two randomised, observer-blind, multinational studies in the northern hemisphere in the 2017-18 (the 18-64 study) and 2018-19 (the 65-plus study) influenza seasons. The 18-64 study was done at 73 sites and the 65-plus study was done at 104 sites, both across Asia, Europe, and North America. In the 18-64 study, inclusion criteria were body-mass index less than 40 kg/m2; age 18-64 years at screening visit; and good health. In the 65-plus study, inclusion criteria were body-mass index of maximum 35 kg/m2; aged 65 years or older at screening visit; not living in a rehabilitation centre or care home; and no acute or evolving medical problems. Participants in the 18-64 study were randomly assigned (1:1) to receive either QVLP vaccine (30 µg haemagglutinin per strain) or placebo. Participants in the 65-plus study were randomly assigned (1:1) to receive QVLP vaccine (30 µg haemagglutinin per strain) or quadrivalent inactivated vaccine (QIV; 15 µg haemagglutinin per strain). The primary outcome in the 18-64 study was absolute vaccine efficacy to prevent laboratory-confirmed, respiratory illness caused by antigenically matched influenza strains. The primary outcome in the 65-plus study was relative vaccine efficacy to prevent laboratory-confirmed influenza-like illness caused by any influenza strain. The primary analyses were done in the per-protocol population and safety was assessed in all participants who received the assigned treatment. These studies are registered with ClinicalTrials.gov (18-64 study NCT03301051; 65-plus study NCT03739112). FINDINGS: In the 18-64 study, between Aug 30, 2017, and Jan 15, 2018, 10 160 participants were randomly assigned to receive either QVLP vaccine (5077 participants) or placebo (5083 participants). The per-protocol population consisted of 4814 participants in the QVLP group and 4812 in the placebo group. The study did not meet its primary endpoint of 70% absolute vaccine efficacy for the QVLP vaccine (35·1% [95% CI 17·9 to 48·7]) against respiratory illness caused by matched strains. 55 (1·1%) of 5064 participants in the QVLP group versus 51 (1·0%) of 5072 in the placebo group had a serious adverse event. Four (0·1%) and six [0·1%] participants had severe treatment-related treatment-emergent adverse events. In the 65-plus study, between Sept 18, 2018, and Feb 22, 2019, 12 794 participants were randomly assigned to receive either QVLP vaccine (6396 participants) or QIV (6398 participants). The per-protocol population consisted of 5996 participants in the QVLP group and 6026 in the QIV group. The study met its primary non-inferiority endpoint with a relative vaccine efficacy of the QVLP vaccine for the prevention of influenza-like illness caused by any strain of 8·8% (-16·7 to 28·7). 263 (4·1%) of 6352 participants in the QVLP group versus 266 (4·2%) of 6366 in the QIV group had serious adverse events (one [<0·1%] vs two [<0·1%] were considered treatment-related); one (<0·1%) versus three (<0·1%) participants had severe treatment-related treatment-emergent adverse events. INTERPRETATION: These efficacy studies are the first large-scale studies of any plant-derived human vaccine. Together, they show that the plant-derived QVLP vaccine can provide substantial protection against respiratory illness and influenza-like illness caused by influenza viruses in adults. QVLP vaccine was well tolerated and no major safety signal arose in participants who received QVLP vaccine across the two studies. FUNDING: Medicago.


Assuntos
Vacinas contra Influenza/imunologia , Influenza Humana/prevenção & controle , Vacinas de Produtos Inativados/imunologia , Adolescente , Adulto , Idoso , Anticorpos Antivirais , Método Duplo-Cego , Feminino , Glicoproteínas de Hemaglutininação de Vírus da Influenza/imunologia , Humanos , Masculino , Pessoa de Meia-Idade , Proteínas de Plantas/imunologia , Adulto Jovem
10.
PLoS One ; 15(10): e0241471, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33112930

RESUMO

Anecdotal evidence showed a negative correlation between Bacille Calmette-Guérin (BCG) vaccination and incidence of COVID-19. Incidence of the disease in children is much lower than in adults. It is hypothesized that BCG and other childhood vaccinations may provide some protection against SARS-CoV-2 infection through trained or adaptive immune responses. Here, we tested whether BCG, Pneumococcal, Rotavirus, Diphtheria, Tetanus, Pertussis, Hepatitis B, Haemophilus influenzae, Hepatitis B, Meningococcal, Measles, Mumps, and Rubella vaccines provide cross-reactive neutralizing antibodies against SARS-CoV-2 in BALB/c mice. Results indicated that none of these vaccines provided antibodies capable of neutralizing SARS-CoV-2 up to seven weeks post vaccination. We conclude that if such vaccines have any role in COVID-19 immunity, this role is not antibody-mediated.


Assuntos
Anticorpos Neutralizantes/biossíntese , Anticorpos Antivirais/biossíntese , Betacoronavirus/imunologia , Infecções por Coronavirus/prevenção & controle , Pandemias/prevenção & controle , Pneumonia Viral/prevenção & controle , Vacinas/imunologia , Adolescente , Adulto , Idoso , Animais , Anticorpos Neutralizantes/sangue , Anticorpos Antivirais/sangue , Criança , Pré-Escolar , Infecções por Coronavirus/imunologia , Reações Cruzadas , Feminino , Humanos , Soros Imunes/imunologia , Imunogenicidade da Vacina , Camundongos , Camundongos Endogâmicos BALB C , Pessoa de Meia-Idade , Testes de Neutralização , Pneumonia Viral/imunologia , Vacinação , Vacinas de Produtos Inativados/imunologia , Vacinas Virais/imunologia , Adulto Jovem
11.
Structure ; 28(11): 1218-1224.e4, 2020 11 03.
Artigo em Inglês | MEDLINE | ID: mdl-33058760

RESUMO

The ongoing global pandemic of coronavirus disease 2019 (COVID-19) resulted from the outbreak of SARS-CoV-2 in December 2019. Currently, multiple efforts are being made to rapidly develop vaccines and treatments to fight COVID-19. Current vaccine candidates use inactivated SARS-CoV-2 viruses; therefore, it is important to understand the architecture of inactivated SARS-CoV-2. We have genetically and structurally characterized ß-propiolactone-inactivated viruses from a propagated and purified clinical strain of SARS-CoV-2. We observed that the virus particles are roughly spherical or moderately pleiomorphic. Although a small fraction of prefusion spikes are found, most spikes appear nail shaped, thus resembling a postfusion state, where the S1 protein of the spike has disassociated from S2. Cryoelectron tomography and subtomogram averaging of these spikes yielded a density map that closely matches the overall structure of the SARS-CoV postfusion spike and its corresponding glycosylation site. Our findings have major implications for SARS-CoV-2 vaccine design, especially those using inactivated viruses.


Assuntos
Betacoronavirus/ultraestrutura , Desinfetantes/farmacologia , Propiolactona/farmacologia , Vírion/efeitos dos fármacos , Animais , Betacoronavirus/efeitos dos fármacos , Betacoronavirus/imunologia , Chlorocebus aethiops , Infecções por Coronavirus/imunologia , Infecções por Coronavirus/prevenção & controle , Microscopia Crioeletrônica , Tomografia com Microscopia Eletrônica , Humanos , Glicoproteína da Espícula de Coronavírus/ultraestrutura , Vacinas de Produtos Inativados/imunologia , Células Vero , Vacinas Virais/imunologia , Vírion/ultraestrutura
12.
Sci Rep ; 10(1): 15643, 2020 09 24.
Artigo em Inglês | MEDLINE | ID: mdl-32973171

RESUMO

As the SARS-CoV-2 pandemic is rapidly progressing, the need for the development of an effective vaccine is critical. A promising approach for vaccine development is to generate, through codon pair deoptimization, an attenuated virus. This approach carries the advantage that it only requires limited knowledge specific to the virus in question, other than its genome sequence. Therefore, it is well suited for emerging viruses, for which we may not have extensive data. We performed comprehensive in silico analyses of several features of SARS-CoV-2 genomic sequence (e.g., codon usage, codon pair usage, dinucleotide/junction dinucleotide usage, RNA structure around the frameshift region) in comparison with other members of the coronaviridae family of viruses, the overall human genome, and the transcriptome of specific human tissues such as lung, which are primarily targeted by the virus. Our analysis identified the spike (S) and nucleocapsid (N) proteins as promising targets for deoptimization and suggests a roadmap for SARS-CoV-2 vaccine development, which can be generalizable to other viruses.


Assuntos
Betacoronavirus/genética , Infecções por Coronavirus/prevenção & controle , Proteínas do Nucleocapsídeo/genética , Pandemias/prevenção & controle , Pneumonia Viral/prevenção & controle , Glicoproteína da Espícula de Coronavírus/genética , Vacinas Virais/imunologia , Sequência de Bases , Infecções por Coronavirus/imunologia , Genoma Viral/genética , Humanos , Proteínas do Nucleocapsídeo/imunologia , Fosfoproteínas , Glicoproteína da Espícula de Coronavírus/imunologia , Vacinas de Produtos Inativados/imunologia , Sequenciamento Completo do Genoma
13.
Curr Opin HIV AIDS ; 15(6): 351-358, 2020 11.
Artigo em Inglês | MEDLINE | ID: mdl-32969973

RESUMO

PURPOSE OF REVIEW: Coronavirus disease-19 (COVID-19) is a highly transmittable and pathogenic pneumonia-causing disease, which is caused by severe acute respiratory syndrome coronavirus-2, resulting in millions of deaths globally. Severe acute respiratory syndrome coronavirus-2 may coexist with human populations for a long time. Therefore, high-effective COVID-19 vaccines are an urgent need. RECENT FINDINGS: Vaccines help in the development of long-lasting humoral or cellular immunity, or both, by exposing individuals to antigens that induce an immunological response and memory prior to infections with live pathogens. New vaccine technologies, such as viral vectors and nucleic acid-based vaccines, which represent highly versatile technologies, may allow for faster vaccine manufacture and scale up production. SUMMARY: We summarized the recent progress made in relation to COVID-19 vaccine development using several promising technologies, with particular emphasis on advancements that are currently at the clinical trial stage.


Assuntos
Infecções por Coronavirus/prevenção & controle , Pandemias/prevenção & controle , Pneumonia Viral/prevenção & controle , Vacinas Virais/imunologia , Adenoviridae/genética , Infecções por Coronavirus/imunologia , Humanos , Vacinação , Vacinas Atenuadas/imunologia , Vacinas de DNA/imunologia , Vacinas de Produtos Inativados/imunologia , Vacinas Sintéticas/imunologia
14.
JAMA ; 324(10): 951-960, 2020 09 08.
Artigo em Inglês | MEDLINE | ID: mdl-32789505

RESUMO

Importance: A vaccine against coronavirus disease 2019 (COVID-19) is urgently needed. Objective: To evaluate the safety and immunogenicity of an investigational inactivated whole-virus COVID-19 vaccine in China. Interventions: In the phase 1 trial, 96 participants were assigned to 1 of the 3 dose groups (2.5, 5, and 10 µg/dose) and an aluminum hydroxide (alum) adjuvant-only group (n = 24 in each group), and received 3 intramuscular injections at days 0, 28, and 56. In the phase 2 trial, 224 adults were randomized to 5 µg/dose in 2 schedule groups (injections on days 0 and 14 [n = 84] vs alum only [n = 28], and days 0 and 21 [n = 84] vs alum only [n = 28]). Design, Setting, and Participants: Interim analysis of ongoing randomized, double-blind, placebo-controlled, phase 1 and 2 clinical trials to assess an inactivated COVID-19 vaccine. The trials were conducted in Henan Province, China, among 96 (phase 1) and 224 (phase 2) healthy adults aged between 18 and 59 years. Study enrollment began on April 12, 2020. The interim analysis was conducted on June 16, 2020, and updated on July 27, 2020. Main Outcomes and Measures: The primary safety outcome was the combined adverse reactions 7 days after each injection, and the primary immunogenicity outcome was neutralizing antibody response 14 days after the whole-course vaccination, which was measured by a 50% plaque reduction neutralization test against live severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Results: Among 320 patients who were randomized (mean age, 42.8 years; 200 women [62.5%]), all completed the trial up to 28 days after the whole-course vaccination. The 7-day adverse reactions occurred in 3 (12.5%), 5 (20.8%), 4 (16.7%), and 6 (25.0%) patients in the alum only, low-dose, medium-dose, and high-dose groups, respectively, in the phase 1 trial; and in 5 (6.0%) and 4 (14.3%) patients who received injections on days 0 and 14 for vaccine and alum only, and 16 (19.0%) and 5 (17.9%) patients who received injections on days 0 and 21 for vaccine and alum only, respectively, in the phase 2 trial. The most common adverse reaction was injection site pain, followed by fever, which were mild and self-limiting; no serious adverse reactions were noted. The geometric mean titers of neutralizing antibodies in the low-, medium-, and high-dose groups at day 14 after 3 injections were 316 (95% CI, 218-457), 206 (95% CI, 123-343), and 297 (95% CI, 208-424), respectively, in the phase 1 trial, and were 121 (95% CI, 95-154) and 247 (95% CI, 176-345) at day 14 after 2 injections in participants receiving vaccine on days 0 and 14 and on days 0 and 21, respectively, in the phase 2 trial. There were no detectable antibody responses in all alum-only groups. Conclusions and Relevance: In this interim report of the phase 1 and phase 2 trials of an inactivated COVID-19 vaccine, patients had a low rate of adverse reactions and demonstrated immunogenicity; the study is ongoing. Efficacy and longer-term adverse event assessment will require phase 3 trials. Trial Registration: Chinese Clinical Trial Registry Identifier: ChiCTR2000031809.


Assuntos
Betacoronavirus/imunologia , Infecções por Coronavirus/prevenção & controle , Imunogenicidade da Vacina , Pandemias/prevenção & controle , Pneumonia Viral/prevenção & controle , Vacinas Virais/imunologia , Adjuvantes Imunológicos/administração & dosagem , Adjuvantes Imunológicos/efeitos adversos , Adolescente , Adulto , Hidróxido de Alumínio/administração & dosagem , Hidróxido de Alumínio/efeitos adversos , Anticorpos Neutralizantes/sangue , Anticorpos Antivirais/sangue , Betacoronavirus/genética , Infecções por Coronavirus/imunologia , Relação Dose-Resposta Imunológica , Método Duplo-Cego , Feminino , Humanos , Injeções Intramusculares , Masculino , Pneumonia Viral/imunologia , Propiolactona , Vacinas de Produtos Inativados/imunologia , Vacinas Virais/administração & dosagem , Vacinas Virais/efeitos adversos , Adulto Jovem
15.
Sheng Wu Gong Cheng Xue Bao ; 36(7): 1378-1385, 2020 Jul 25.
Artigo em Chinês | MEDLINE | ID: mdl-32748595

RESUMO

Listeria monocytogenes (Lm) is zoonotic pathogen that can cause listeriosis, and vaccine is one of the effective methods to prevent this pathogen infection. In this study, we developed a novel vaccine that is a mixture of inactivated bacteria and Montanide™ ISA 61 VG, a mineral oil adjuvant, and evaluated the safety and immune response characteristics of this vaccine. The mice immunized with the ISA 61 VG adjuvant had high safety, and it could induce significantly higher titer of anti-listeriolysin O (LLO) antibody and higher value of IgG2a/IgG1 ratio compared with the group without the adjuvant. In particular, it could provide 100% immune protection against lethal doses of Lm challenge in mice. In summary, ISA 61VG adjuvant significantly enhanced the ability of inactivated listeria vaccine to induce humoral and cellular immune responses, thereby enhanced the protective immune response in the host, and it is a potential vaccine candidate for the prevention of Lm infection in humans and animals.


Assuntos
Adjuvantes Imunológicos , Proteínas Hemolisinas , Imunidade Celular , Listeria monocytogenes , Listeriose , Adjuvantes Imunológicos/farmacologia , Animais , Proteínas Hemolisinas/imunologia , Proteínas Hemolisinas/farmacologia , Imunidade Celular/efeitos dos fármacos , Listeria monocytogenes/imunologia , Listeriose/prevenção & controle , Camundongos , Camundongos Endogâmicos BALB C , Vacinas de Produtos Inativados/imunologia
17.
Lancet Infect Dis ; 20(9): 1061-1070, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32618279

RESUMO

BACKGROUND: The development of an effective vaccine against Zika virus remains a public health priority. A Zika purified inactivated virus (ZPIV) vaccine candidate has been shown to protect animals against Zika virus challenge and to be well tolerated and immunogenic in humans up to 8 weeks of follow-up. We aimed to assess the safety and immunogenicity of ZPIV in humans up to 52 weeks of follow-up when given via standard or accelerated vaccination schedules. METHODS: We did a single-centre, double-blind, randomised controlled, phase 1 trial in healthy adults aged 18-50 years with no known history of flavivirus vaccination or infection at Beth Israel Deaconess Medical Center in Boston, MA, USA. Participants were sequentially enrolled into one of three groups: ZPIV given at weeks 0 and 4 (standard regimen), weeks 0 and 2 (accelerated regimen), or week 0 alone (single-dose regimen). Within each group, participants were randomly assigned using a computer-generated randomisation schedule to receive an intramuscular injection of 5 µg ZPIV or saline placebo, in a ratio of 5:1. The sponsor, clinical staff, investigators, participants, and laboratory personnel were masked to treatment assignment. The primary endpoint was safety up to day 364 after final dose administration, and secondary endpoints were proportion of participants with positive humoral immune responses (50% microneutralisation titre [MN50] ≥100) and geometric mean MN50 at observed peak response (ie, the highest neutralising antibody level observed for an individual participant across all timepoints) and week 28. All participants who received at least one dose of ZPIV or placebo were included in the safety population; the analysis of immunogenicity at observed peak included all participants who received at least one dose of ZPIV or placebo and had any adverse events or immunogenicity data after dosing. The week 28 immunogenicity analysis population consisted of all participants who received ZPIV or placebo and had immunogenicity data available at week 28. This trial is registered with ClinicalTrials.gov, NCT02937233. FINDINGS: Between Dec 8, 2016, and May 17, 2017, 12 participants were enrolled into each group and then randomly assigned to vaccine (n=10) or placebo (n=2). There were no serious or grade 3 treatment-related adverse events. The most common reactions among the 30 participants who received the vaccine were injection-site pain (24 [80%]), fatigue (16 [53%]), and headache (14 [46%]). A positive response at observed peak titre was detected in all participants who received ZPIV via the standard regimen, in eight (80%) of ten participants who received ZPIV via the accelerated regimen, and in none of the ten participants who received ZPIV via the single-dose regimen. The geometric mean of all individual participants' observed peak values was 1153·9 (95% CI 455·2-2925·2) in the standard regimen group, 517·7 (142·9-1875·6) in the accelerated regimen group, and 6·3 (3·7-10·8) in the single-dose regimen group. At week 28, a positive response was observed in one (13%) of eight participants who received ZPIV via the standard regimen and in no participant who received ZPIV via the accelerated (n=7) or single-dose (n=10) regimens. The geomteric mean titre (GMT) at this timepoint was 13·9 (95% CI 3·5-55·1) in the standard regimen group and 6·9 (4·0-11·9) in the accelerated regimen group; antibody titres were undetectable at 28 weeks in participants who received ZPIV via the single-dose regimen. For all vaccine schedules, GMTs peaked 2 weeks after the final vaccination and declined to less than 100 by study week 16. There was no difference in observed peak GMTs between the standard 4-week and the accelerated 2-week boosting regimens (p=0·4494). INTERPRETATION: ZPIV was safe and well tolerated in humans up to 52 weeks of follow-up. ZPIV immunogenicity required two doses and was not durable. Additional studies of ZPIV to optimise dosing schedules are ongoing. FUNDING: The Henry M Jackson Foundation for the Advancement of Military Medicine.


Assuntos
Imunogenicidade da Vacina , Vacinas de Produtos Inativados/imunologia , Vacinas Virais/imunologia , Infecção por Zika virus/prevenção & controle , Zika virus/imunologia , Adolescente , Adulto , Feminino , Humanos , Esquemas de Imunização , Masculino , Pessoa de Meia-Idade , Vacinas de Produtos Inativados/administração & dosagem , Vacinas de Produtos Inativados/efeitos adversos , Vacinas Virais/administração & dosagem , Vacinas Virais/efeitos adversos , Adulto Jovem
18.
Microbes Infect ; 22(6-7): 245-253, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32437926

RESUMO

The global pandemic of COVID-19 caused by SARS-CoV-2 (also known as 2019-nCoV and HCoV-19) has posed serious threats to public health and economic stability worldwide, thus calling for development of vaccines against SARS-CoV-2 and other emerging and reemerging coronaviruses. Since SARS-CoV-2 and SARS-CoV have high similarity of their genomic sequences and share the same cellular receptor (ACE2), it is essential to learn the lessons and experiences from the development of SARS-CoV vaccines for the development of SARS-CoV-2 vaccines. In this review, we summarized the current knowledge on the advantages and disadvantages of the SARS-CoV vaccine candidates and prospected the strategies for the development of safe, effective and broad-spectrum coronavirus vaccines for prevention of infection by currently circulating SARS-CoV-2 and other emerging and reemerging coronaviruses that may cause future epidemics or pandemics.


Assuntos
Infecções por Coronavirus/prevenção & controle , Pandemias/prevenção & controle , Pneumonia Viral/prevenção & controle , Síndrome Respiratória Aguda Grave/prevenção & controle , Vacinas Virais/imunologia , Animais , Betacoronavirus/genética , Infecções por Coronavirus/classificação , Infecções por Coronavirus/imunologia , Proteção Cruzada , Humanos , Pneumonia Viral/imunologia , Síndrome Respiratória Aguda Grave/imunologia , Vacinas de Produtos Inativados/imunologia , Vacinas Virais/classificação
19.
Science ; 369(6499): 77-81, 2020 07 03.
Artigo em Inglês | MEDLINE | ID: mdl-32376603

RESUMO

The coronavirus disease 2019 (COVID-19) pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has resulted in an unprecedented public health crisis. Because of the novelty of the virus, there are currently no SARS-CoV-2-specific treatments or vaccines available. Therefore, rapid development of effective vaccines against SARS-CoV-2 are urgently needed. Here, we developed a pilot-scale production of PiCoVacc, a purified inactivated SARS-CoV-2 virus vaccine candidate, which induced SARS-CoV-2-specific neutralizing antibodies in mice, rats, and nonhuman primates. These antibodies neutralized 10 representative SARS-CoV-2 strains, suggesting a possible broader neutralizing ability against other strains. Three immunizations using two different doses, 3 or 6 micrograms per dose, provided partial or complete protection in macaques against SARS-CoV-2 challenge, respectively, without observable antibody-dependent enhancement of infection. These data support the clinical development and testing of PiCoVacc for use in humans.


Assuntos
Anticorpos Neutralizantes/sangue , Anticorpos Antivirais/sangue , Betacoronavirus/imunologia , Infecções por Coronavirus/prevenção & controle , Pandemias/prevenção & controle , Pneumonia Viral/prevenção & controle , Vacinas Virais , Animais , Anticorpos Neutralizantes/biossíntese , Anticorpos Neutralizantes/imunologia , Anticorpos Antivirais/biossíntese , Anticorpos Antivirais/imunologia , Betacoronavirus/isolamento & purificação , Chlorocebus aethiops , Infecções por Coronavirus/imunologia , Infecções por Coronavirus/virologia , Relação Dose-Resposta Imunológica , Feminino , Imunogenicidade da Vacina , Imunoglobulina G/biossíntese , Imunoglobulina G/sangue , Imunoglobulina G/imunologia , Macaca mulatta , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Projetos Piloto , Pneumonia Viral/virologia , Ratos , Ratos Wistar , Vacinas de Produtos Inativados/administração & dosagem , Vacinas de Produtos Inativados/efeitos adversos , Vacinas de Produtos Inativados/imunologia , Células Vero , Carga Viral , Vacinas Virais/administração & dosagem , Vacinas Virais/efeitos adversos , Vacinas Virais/imunologia
20.
Vet Q ; 40(1): 183-189, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-32448096

RESUMO

Background: Outbreaks of porcine epidemic diarrhea virus (PEDV) infection have re-emerged and spread rapidly worldwide, resulting in significant economic losses. Vaccination is the best way to prevent PEDV infection in young piglets.Objective: To enhance the efficacy of an inactivated vaccine against PEDV, we evaluated the adjuvant properties of Fc domain of IgG.Methods: Fifteen crossbred gilts (180 ∼ 210 days old) were used. Five pigs in group 1 were intramuscularly vaccinated twice at 4 weeks and 2 weeks prior to farrowing with 106 TCID50 of inactivated PEDV. Five pigs in group 2 were intramuscularly vaccinated twice at 4 weeks and 2 weeks prior to farrowing with 106 TCID50 of inactivated PEDV-sFc. Five pigs in group 3 were not vaccinated and served as negative controls. Serum samples were collected at farrowing and subjected to ELISA, a serum neutralizing (SN) test, and a cytokine assay. Statistical analysis was performed by a two-tailed unpaired t-test.Results: Vero cells expressing swine IgG Fc on its surface was established. When PEDV was propagated in the cells expressing the swine Fc, PEDV virion incorporated the Fc. Immunization of pigs with inactivated PEDV harbouring Fc induced significantly higher antibody production against PEDV, comparing to the immunization with normal inactivated PEDV. In addition, we observed significantly increased IFN-γ levels in sera.Conclusion: Our results indicate that Fc molecule facilitate immune responses and PEDV harbouring Fc molecule could be a possible vaccine candidate. However, a challenge experiment would be needed to investigate the protective efficacy of PEDV harbouring Fc.


Assuntos
Infecções por Coronavirus/veterinária , Fragmentos Fc das Imunoglobulinas/imunologia , Imunoglobulina G/imunologia , Vírus da Diarreia Epidêmica Suína/imunologia , Doenças dos Suínos/imunologia , Adjuvantes Imunológicos , Animais , Chlorocebus aethiops , Infecções por Coronavirus/imunologia , Feminino , Imunização , Testes de Neutralização , Sus scrofa , Suínos , Doenças dos Suínos/virologia , Vacinas de Produtos Inativados/imunologia , Células Vero , Vacinas Virais/imunologia
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