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2.
BMC Public Health ; 20(1): 1374, 2020 Sep 09.
Artigo em Inglês | MEDLINE | ID: mdl-32907562

RESUMO

BACKGROUND: Influenza epidemics significantly weight on the Brazilian healthcare system and its society. Public health authorities have progressively expanded recommendations for vaccination against influenza, particularly to the pediatric population. However, the potential mismatch between the trivalent influenza vaccine (TIV) strains and those circulating during the season remains an issue. Quadrivalent vaccines improves vaccines effectiveness by preventing any potential mismatch on influenza B lineages. METHODS: We evaluate the public health and economic benefits of the switch from TIV to QIV for the pediatric influenza recommendation (6mo-5yo) by using a dynamic epidemiological model able to consider the indirect impact of vaccination. Results of the epidemiological model are then imputed in a health-economic model adapted to the Brazilian context. We perform deterministic and probabilistic sensitivity analysis to account for both epidemiological and economical sources of uncertainty. RESULTS: Our results show that switching from TIV to QIV in the Brazilian pediatric population would prevent 406,600 symptomatic cases, 11,300 hospitalizations and almost 400 deaths by influenza season. This strategy would save 3400 life-years yearly for an incremental direct cost of R$169 million per year, down to R$86 million from a societal perspective. Incremental cost-effectiveness ratios for the switch would be R$49,700 per life-year saved and R$26,800 per quality-adjusted life-year gained from a public payer perspective, and even more cost-effective from a societal perspective. Our results are qualitatively similar in our sensitivity analysis. CONCLUSIONS: Our analysis shows that switching from TIV to QIV to protect children aged 6mo to 5yo in the Brazilian influenza epidemiological context could have a strong public health impact and represent a cost-effective strategy from a public payer perspective, and a highly cost-effective one from a societal perspective.


Assuntos
Análise Custo-Benefício , Vacinas contra Influenza , Influenza Humana/prevenção & controle , Saúde Pública , Vacinação , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Brasil/epidemiologia , Criança , Pré-Escolar , Economia Médica , Feminino , Hospitalização/economia , Humanos , Lactente , Vírus da Influenza B/classificação , Vírus da Influenza B/imunologia , Vacinas contra Influenza/economia , Vacinas contra Influenza/imunologia , Influenza Humana/economia , Influenza Humana/epidemiologia , Influenza Humana/virologia , Pessoa de Meia-Idade , Modelos Econômicos , Anos de Vida Ajustados por Qualidade de Vida , Estações do Ano , Incerteza , Vacinação/economia , Adulto Jovem
3.
J Am Soc Nephrol ; 31(9): 2117-2121, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32817310

RESUMO

BACKGROUND: Racial and ethnic disparities in vaccination rates for seasonal influenza exist. Whether such disparities extend to patients with ESKD, who simultaneously are at risk for complications of infection and have extensive contact with health care providers, has not been investigated. METHODS: To determine whether the proportion of patients vaccinated at a dialysis facility differs according to the facility's racial and ethnic composition, we examined dialysis facility data reported to the Centers for Medicare and Medicaid Services. The main outcome was the proportion of facility patients vaccinated for influenza among 6735 Medicare-certified facilities operating between 2014 and 2017. RESULTS: Among dialysis facilities, the mean percentage of patients vaccinated during the influenza season was 72.1%. Facilities with higher proportions of Black and Hispanic patients had significantly lower vaccination percentages than less diverse facilities. The average proportion of patients vaccinated at each facility decreased significantly from 2014 to 2017 (a decrease of 1.05% vaccinated per year) and decreased significantly more so among facilities with higher minority proportions. The share of vaccinated patients in facilities in the quartile with the highest proportion of Black patients decreased 1.21% per year compared with a decrease of 0.88% per year in facilities in the quartile with the lowest proportion of Black patients. We found similar trends for Hispanic patients. CONCLUSIONS: Rates of seasonal influenza vaccination are modestly but significantly lower among dialysis facilities with larger proportions of minority patients, and the gap seems to be widening over time. As wide-scale vaccination efforts grow more urgent amid the current COVID-19 pandemic, these disparities must be addressed to protect patients and communities equitably.


Assuntos
Disparidades em Assistência à Saúde , Vacinas contra Influenza/imunologia , Diálise Renal , Vacinação/estatística & dados numéricos , Grupo com Ancestrais do Continente Africano , Idoso , Betacoronavirus , Infecções por Coronavirus/epidemiologia , Humanos , Falência Renal Crônica/terapia , Pessoa de Meia-Idade , Pandemias , Pneumonia Viral/epidemiologia , Estações do Ano
4.
Euro Surveill ; 25(25)2020 06.
Artigo em Inglês | MEDLINE | ID: mdl-32613937

RESUMO

The advent of COVID-19, has posed a risk that human respiratory samples containing human influenza viruses may also contain SARS-CoV-2. This potential risk may lead to SARS-CoV-2 contaminating conventional influenza vaccine production platforms as respiratory samples are used to directly inoculate embryonated hen's eggs and continuous cell lines that are used to isolate and produce influenza vaccines. We investigated the ability of these substrates to propagate SARS-CoV-2 and found that neither could support SARS-CoV-2 replication.


Assuntos
Galinhas/imunologia , Coronavirus/fisiologia , Vacinas contra Influenza/imunologia , Influenza Humana/prevenção & controle , Células Madin Darby de Rim Canino , Receptores Virais/metabolismo , Cultura de Vírus/métodos , Replicação Viral , Animais , Betacoronavirus , Linhagem Celular , Galinhas/virologia , Infecções por Coronavirus/epidemiologia , Infecções por Coronavirus/virologia , Cães , Ovos , Humanos , Pandemias , Pneumonia Viral , Síndrome Respiratória Aguda Grave
5.
PLoS One ; 15(7): e0234827, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32645112

RESUMO

BACKGROUND: The most important factor influencing maternal vaccination uptake is healthcare professional (HCP) recommendation. However, where data are available, one-third of pregnant women remain unvaccinated despite receiving a recommendation. Therefore, it is essential to understand the significance of other factors and distinguish between vaccines administered routinely and during outbreaks. This is the first systematic review and meta-analysis (PROSPERO: CRD 42019118299) to examine the strength of the relationships between identified factors and maternal vaccination uptake. METHODS: We searched MEDLINE, Embase Classic & Embase, PsycINFO, CINAHL Plus, Web of Science, IBSS, LILACS, AfricaWideInfo, IMEMR, and Global Health databases for studies reporting factors that influence maternal vaccination. We used random-effects models to calculate pooled odds ratios (OR) of being vaccinated by vaccine type. FINDINGS: We screened 17,236 articles and identified 120 studies from 30 countries for inclusion. Of these, 49 studies were eligible for meta-analysis. The odds of receiving a pertussis or influenza vaccination were ten to twelve-times higher among pregnant women who received a recommendation from HCPs. During the 2009 influenza pandemic an HCP recommendation increased the odds of antenatal H1N1 vaccine uptake six times (OR 6.76, 95% CI 3.12-14.64, I2 = 92.00%). Believing there was potential for vaccine-induced harm had a negative influence on seasonal (OR 0.22, 95% CI 0.11-0.44 I2 = 84.00%) and pandemic influenza vaccine uptake (OR 0.16, 95% CI 0.09-0.29, I2 = 89.48%), reducing the odds of being vaccinated five-fold. Combined with our qualitative analysis the relationship between the belief in substantial disease risk and maternal seasonal and pandemic influenza vaccination uptake was limited. CONCLUSIONS: The effect of an HCP recommendation during an outbreak, whilst still powerful, may be muted by other factors. This requires further research, particularly when vaccines are novel. Public health campaigns which centre on the protectiveness and safety of a maternal vaccine rather than disease threat alone may prove beneficial.


Assuntos
Aceitação pelo Paciente de Cuidados de Saúde/psicologia , Gestantes/psicologia , Vacinação/psicologia , Adulto , Tomada de Decisões , Feminino , Pessoal de Saúde/psicologia , Humanos , Vírus da Influenza A Subtipo H1N1/imunologia , Vacinas contra Influenza/imunologia , Influenza Humana/prevenção & controle , Razão de Chances , Gravidez , Inquéritos e Questionários
6.
Proc Natl Acad Sci U S A ; 117(30): 17957-17964, 2020 07 28.
Artigo em Inglês | MEDLINE | ID: mdl-32661157

RESUMO

There is a need for improved influenza vaccines. In this study we compared the antibody responses in humans after vaccination with an AS03-adjuvanted versus nonadjuvanted H5N1 avian influenza virus inactivated vaccine. Healthy young adults received two doses of either formulation 3 wk apart. We found that AS03 significantly enhanced H5 hemagglutinin (HA)-specific plasmablast and antibody responses compared to the nonadjuvanted vaccine. Plasmablast response after the first immunization was exclusively directed to the conserved HA stem region and came from memory B cells. Monoclonal antibodies (mAbs) derived from these plasmablasts had high levels of somatic hypermutation (SHM) and recognized the HA stem region of multiple influenza virus subtypes. Second immunization induced a plasmablast response to the highly variable HA head region. mAbs derived from these plasmablasts exhibited minimal SHM (naive B cell origin) and largely recognized the HA head region of the immunizing H5N1 strain. Interestingly, the antibody response to H5 HA stem region was much lower after the second immunization, and this suppression was most likely due to blocking of these epitopes by stem-specific antibodies induced by the first immunization. Taken together, these findings show that an adjuvanted influenza vaccine can substantially increase antibody responses in humans by effectively recruiting preexisting memory B cells as well as naive B cells into the response. In addition, we show that high levels of preexisting antibody can have a negative effect on boosting. These findings have implications toward the development of a universal influenza vaccine.


Assuntos
Adjuvantes Imunológicos , Linfócitos B/imunologia , Reações Cruzadas/imunologia , Memória Imunológica , Virus da Influenza A Subtipo H5N1/imunologia , Vacinas contra Influenza/imunologia , Influenza Humana/prevenção & controle , Anticorpos Antivirais/imunologia , Formação de Anticorpos/imunologia , Especificidade de Anticorpos/imunologia , Linfócitos B/metabolismo , Epitopos de Linfócito B/imunologia , Feminino , Humanos , Imunização Secundária , Masculino , Plasmócitos/imunologia , Plasmócitos/metabolismo
7.
Proc Natl Acad Sci U S A ; 117(30): 17757-17763, 2020 07 28.
Artigo em Inglês | MEDLINE | ID: mdl-32669430

RESUMO

Vaccination has been used to control the spread of seasonal flu; however, the virus continues to evolve and escape from host immune response through mutation and increasing glycosylation. Efforts have been directed toward development of a universal vaccine with broadly protective activity against multiple influenza strains and subtypes. Here we report the design and evaluation of various chimeric vaccines based on the most common avian influenza H5 and human influenza H1 sequences. Of these constructs, the chimeric HA (cHA) vaccine with consensus H5 as globular head and consensus H1 as stem was shown to elicit broadly protective CD4+ and CD8+ T cell responses. Interestingly, the monoglycosylated cHA (cHAmg) vaccine with GlcNAc on each glycosite induced more stem-specific antibodies, with higher antibody-dependent cellular cytotoxicity (ADCC), and better neutralizing and stronger cross-protection activities against H1, H3, H5, and H7 strains and subtypes. Moreover, the cHAmg vaccine combined with a glycolipid adjuvant designed for class switch further enhanced the vaccine efficacy with more IFN-γ, IL-4, and CD8+ memory T cells produced.


Assuntos
Linfócitos T CD4-Positivos/imunologia , Linfócitos T CD8-Positivos/imunologia , Proteção Cruzada/imunologia , Glicoproteínas de Hemaglutininação de Vírus da Influenza/imunologia , Vacinas contra Influenza/imunologia , Influenza Humana/prevenção & controle , Orthomyxoviridae/imunologia , Animais , Anticorpos Neutralizantes/imunologia , Anticorpos Antivirais/imunologia , Citotoxicidade Celular Dependente de Anticorpos , Linfócitos T CD4-Positivos/metabolismo , Linfócitos T CD8-Positivos/metabolismo , Modelos Animais de Doenças , Glicoproteínas de Hemaglutininação de Vírus da Influenza/química , Humanos , Influenza Humana/virologia , Camundongos , Modelos Moleculares , Testes de Neutralização , Orthomyxoviridae/classificação , Proteínas Recombinantes de Fusão/química , Proteínas Recombinantes de Fusão/imunologia , Relação Estrutura-Atividade , Vacinação
8.
Curr Top Microbiol Immunol ; 428: 31-87, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32648034

RESUMO

Development of vaccines to highly variable viruses such as Human Immunodeficiency Virus and influenza A viruses faces multiple challenges. In this article, these challenges are described and reverse vaccinology approaches to generate universal vaccines against both pathogens are laid out and compared.


Assuntos
Vacinas contra a AIDS/imunologia , Anticorpos Antivirais/imunologia , Anticorpos Amplamente Neutralizantes/imunologia , HIV/imunologia , Vacinas contra Influenza/imunologia , Orthomyxoviridae/imunologia , Vacinologia , Vacinas contra a AIDS/química , HIV/química , Humanos , Vacinas contra Influenza/química , Orthomyxoviridae/química
9.
PLoS One ; 15(7): e0236527, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32716918

RESUMO

OBJECTIVE: The aim of the present study was to investigate whether anti-vaccination attitudes and behavior, and positive attitudes to complementary and alternative medicine (CAM), are driven by trait reactance and a distrust in medical doctors. METHODS: The sample consisted of 770 Finnish parents who filled out an online survey. Structural equation modeling (SEM) was used to examine if trait reactance plays a role in vaccination decisions, vaccine attitudes, and in the use of CAM, and whether that relationship is mediated by trust in medical doctors. RESULTS: Parents with higher trait reactance had lower trust in doctors, more negative attitudes to vaccines, a higher likelihood of not accepting vaccines for their children and themselves, and a higher likelihood to use CAM treatments that are not included in evidence-based medicine. Our analyses also revealed associations between vaccination behavior and CAM use and vaccine attitudes and CAM use, but there was no support for the previous notion that these associations would be explained by trait reactance and trust in doctors. CONCLUSIONS: Taken together, higher trait reactance seems to be relevant for attitudes and behaviors that go against conventional medicine, because trait reactance is connected to a distrust in medical doctors. Our findings also suggest that high trait reactance and low trust in doctors function differently for different people: For some individuals they might be associated with anti-vaccination attitudes and behavior, while for others they might be related to CAM use. We speculate that this is because people differ in what is important to them, leading them to react against different aspects of conventional medicine.


Assuntos
Terapias Complementares , Conhecimentos, Atitudes e Prática em Saúde , Pais/psicologia , Vacinação/psicologia , Adulto , Criança , Pré-Escolar , Feminino , Finlândia , Humanos , Vacinas contra Influenza/imunologia , Influenza Humana/prevenção & controle , Internet , Masculino , Relações Médico-Paciente , Inquéritos e Questionários
10.
BMC Bioinformatics ; 21(1): 256, 2020 Jun 19.
Artigo em Inglês | MEDLINE | ID: mdl-32560624

RESUMO

BACKGROUND: In 2009, a novel influenza vaccine was distributed worldwide to combat the H1N1 influenza "swine flu" pandemic. However, antibodies induced by the vaccine display differences in their specificity and cross-reactivity dependent on pre-existing immunity. Here, we present a computational model that can capture the effect of pre-existing immunity on influenza vaccine responses. The model predicts the region of the virus hemagglutinin (HA) protein targeted by antibodies after vaccination as well as the level of cross-reactivity induced by the vaccine. We tested our model by simulating a scenario similar to the 2009 pandemic vaccine and compared the results to antibody binding data obtained from human subjects vaccinated with the monovalent 2009 H1N1 influenza vaccine. RESULTS: We found that both specificity and cross-reactivity of the antibodies induced by the 2009 H1N1 influenza HA protein were affected by the viral strain the individual was originally exposed. Specifically, the level of antigenic relatedness between the original exposure HA antigen and the 2009 HA protein affected antigenic-site immunodominance. Moreover, antibody cross-reactivity was increased when the individual's pre-existing immunity was specific to an HA protein antigenically distinct from the 2009 pandemic strain. Comparison of simulation data with antibody binding data from human serum samples demonstrated qualitative and quantitative similarities between the model and real-life immune responses to the 2009 vaccine. CONCLUSION: We provide a novel method to evaluate expected outcomes in antibody specificity and cross-reactivity after influenza vaccination in individuals with different influenza HA antigen exposure histories. The model produced similar outcomes as what has been previously reported in humans after receiving the 2009 influenza pandemic vaccine. Our results suggest that differences in cross-reactivity after influenza vaccination should be expected in individuals with different exposure histories.


Assuntos
Anticorpos Antivirais/imunologia , Glicoproteínas de Hemaglutininação de Vírus da Influenza/imunologia , Vírus da Influenza A Subtipo H1N1/imunologia , Vacinas contra Influenza/imunologia , Modelos Imunológicos , Sequência de Aminoácidos , Anticorpos Antivirais/sangue , Antígenos Virais/química , Antígenos Virais/imunologia , Simulação por Computador , Reações Cruzadas , Glicoproteínas de Hemaglutininação de Vírus da Influenza/química , Humanos
11.
Science ; 368(6497): 1335-1340, 2020 06 19.
Artigo em Inglês | MEDLINE | ID: mdl-32554590

RESUMO

The discovery and characterization of broadly neutralizing human antibodies (bnAbs) to the highly conserved stem region of influenza hemagglutinin (HA) have contributed to considerations of a universal influenza vaccine. However, the potential for resistance to stem bnAbs also needs to be more thoroughly evaluated. Using deep mutational scanning, with a focus on epitope residues, we found that the genetic barrier to resistance to stem bnAbs is low for the H3 subtype but substantially higher for the H1 subtype owing to structural differences in the HA stem. Several strong resistance mutations in H3 can be observed in naturally circulating strains and do not reduce in vitro viral fitness and in vivo pathogenicity. This study highlights a potential challenge for development of a truly universal influenza vaccine.


Assuntos
Anticorpos Neutralizantes/imunologia , Anticorpos Antivirais/imunologia , Glicoproteínas de Hemaglutininação de Vírus da Influenza/imunologia , Tolerância Imunológica/genética , Vírus da Influenza A Subtipo H1N1/imunologia , Vírus da Influenza A Subtipo H3N2/imunologia , Glicoproteínas de Hemaglutininação de Vírus da Influenza/química , Glicoproteínas de Hemaglutininação de Vírus da Influenza/genética , Humanos , Epitopos Imunodominantes/química , Epitopos Imunodominantes/genética , Epitopos Imunodominantes/imunologia , Vírus da Influenza A Subtipo H1N1/genética , Vírus da Influenza A Subtipo H3N2/genética , Vacinas contra Influenza/genética , Vacinas contra Influenza/imunologia , Mutação
12.
PLoS One ; 15(6): e0233632, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32492039

RESUMO

Increasing pandemic influenza vaccine manufacturing capacity is considered strategic by WHO. Adjuvant use is key in this strategy in order to spare the vaccine doses and by increasing immune protection. We describe here the production and stability studies of a squalene based oil-in-water emulsion, adjuvant IB160, and the immune response of the H7N9 vaccine combined with IB160. To qualify the production of IB160 we produced 10 consistency lots of IB160 and the average results were: pH 6.4±0.05; squalene 48.8±.0.03 mg/ml; osmolality 47.6±6.9 mmol/kg; Z-average 157±2 nm, with polydispersity index (PDI) of 0.085±0.024 and endotoxin levels <0.5 EU/mL. The emulsion particle size was stable for at least six months at 25°C and 24 months at 4-8°C. Two doses of H7N9 vaccine formulated at 7.5 µg/dose or 15 µg/dose with adjuvant IB160 showed a significant increase of hemagglutination inhibition (HAI) titers in sera of immunized BALB/c mice when compared to control sera from animals immunized with the H7N9 antigens without adjuvant. Thus the antigen-sparing capacity of IB160 can potentially increase the production of the H7N9 pandemic vaccine and represents an important achievement for preparedness against pandemic influenza and a successful North (IDRI) to South (Butantan Institute) technology transfer for the production of the adjuvant emulsion IB160.


Assuntos
Adjuvantes Farmacêuticos/síntese química , Emulsões/síntese química , Subtipo H7N9 do Vírus da Influenza A/imunologia , Influenza Humana/epidemiologia , Influenza Humana/prevenção & controle , Infecções por Orthomyxoviridae/prevenção & controle , Pandemias/prevenção & controle , Adjuvantes Farmacêuticos/química , Animais , Brasil/epidemiologia , Estabilidade de Medicamentos , Emulsões/química , Testes de Inibição da Hemaglutinação , Humanos , Vacinas contra Influenza/imunologia , Influenza Humana/virologia , Camundongos , Camundongos Endogâmicos BALB C , Infecções por Orthomyxoviridae/virologia , Polissorbatos/química , Esqualeno/química , Transferência de Tecnologia , Vacinação/métodos
13.
PLoS Comput Biol ; 16(6): e1007989, 2020 06.
Artigo em Inglês | MEDLINE | ID: mdl-32542015

RESUMO

Influenza epidemics cause substantial morbidity and mortality every year worldwide. Currently, two influenza A subtypes, A(H1N1) and A(H3N2), and type B viruses co-circulate in humans and infection with one type/subtype could provide cross-protection against the others. However, it remains unclear how such ecologic competition via cross-immunity and antigenic mutations that allow immune escape impact influenza epidemic dynamics at the population level. Here we develop a comprehensive model-inference system and apply it to study the evolutionary and epidemiological dynamics of the three influenza types/subtypes in Hong Kong, a city of global public health significance for influenza epidemic and pandemic control. Utilizing long-term influenza surveillance data since 1998, we are able to estimate the strength of cross-immunity between each virus-pairs, the timing and frequency of punctuated changes in population immunity in response to antigenic mutations in influenza viruses, and key epidemiological parameters over the last 20 years including the 2009 pandemic. We find evidence of cross-immunity in all types/subtypes, with strongest cross-immunity from A(H1N1) against A(H3N2). Our results also suggest that A(H3N2) may undergo antigenic mutations in both summers and winters and thus monitoring the virus in both seasons may be important for vaccine development. Overall, our study reveals intricate epidemiological interactions and underscores the importance of simultaneous monitoring of population immunity, incidence rates, and viral genetic and antigenic changes.


Assuntos
Vírus da Influenza A Subtipo H1N1/fisiologia , Vírus da Influenza A Subtipo H3N2/fisiologia , Influenza Humana/epidemiologia , Hong Kong/epidemiologia , Humanos , Vírus da Influenza A Subtipo H1N1/imunologia , Vírus da Influenza A Subtipo H3N2/imunologia , Vacinas contra Influenza/administração & dosagem , Vacinas contra Influenza/imunologia , Influenza Humana/prevenção & controle , Influenza Humana/virologia
14.
DNA Cell Biol ; 39(9): 1730-1740, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32580635

RESUMO

Polyinosinic-polycytidylic acid (PIC) is a potent double-stranded RNA (dsRNA) adjuvant useful in intranasal influenza vaccination. In mice, the intensity and duration of immune responses to PIC correlated with the double-stranded chain length. A rational method to avoid PIC chain extension in PIC production is to use multiple short poly(I) molecules and one long poly(C) molecule for PIC assembly. In this study, we elucidate that a newly developed uPIC100-400 molecule comprising multiple 0.1 kb poly(I) molecules and one 0.4 kb poly(C) molecule effectively enhanced the immune responses in mice, by preventing the challenged viral propagation and inducing hemagglutinin-specific IgA, after intranasal A(H1N1)pdm09 influenza vaccination. Reduced intraperitoneal toxicity of PIC prepared with multiple short poly(I) molecules in mice indicates the widened effective range of uPIC100-400 as an adjuvant. In contrast to uPIC100-400, the PIC molecule comprising multiple 0.05 kb poly(I) molecules failed to elicit mouse mucosal immunity. These results were consistent with TLR3 response but not retinoic acid inducible gene I (RIG-I)-like receptor response in the cell assays, which suggests that the adjuvant effect of PIC in mouse intranasal immunization depends on TLR3 signaling. In conclusion, the double-stranded PIC with reduced toxicity developed in this study would contribute to the development of PIC-adjuvanted vaccines.


Assuntos
Adjuvantes Imunológicos/uso terapêutico , Indutores de Interferon/uso terapêutico , Infecções por Orthomyxoviridae/imunologia , Poli I-C/uso terapêutico , Receptor 3 Toll-Like/metabolismo , Vacinação/métodos , Adjuvantes Imunológicos/administração & dosagem , Adjuvantes Imunológicos/efeitos adversos , Animais , Células Cultivadas , Feminino , Glicoproteínas de Hemaglutininação de Vírus da Influenza/imunologia , Imunoglobulina A/imunologia , Vacinas contra Influenza/imunologia , Indutores de Interferon/administração & dosagem , Indutores de Interferon/efeitos adversos , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Endogâmicos C57BL , Infecções por Orthomyxoviridae/prevenção & controle , Poli I-C/administração & dosagem , Poli I-C/efeitos adversos , Transdução de Sinais
16.
PLoS One ; 15(6): e0234869, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32579578

RESUMO

The continuous variation of the seasonal influenza viruses, particularly A(H1N1)pdm09, persistently threatens human life and health around the world. In local areas of southwest china, the large time-scale genomic research on A(H1N1)pdm09 is still insufficient. Here, we sequenced 45 whole-genome sequences of influenza A(H1N1)pdm09 viruses in Lincang, China, from 2014 to 2018, by next-generation sequencing technology to characterize molecular mechanisms of their origin and evolution. Our phylogenetic analyses suggest that the A(H1N1)pdm09 strains circulating in Lincang belong to clade 6B and the subclade 6B.1A predominates in 2018. Further, the strains in 2018 possess elevated evolutionary rate as compared to strains in other years. Several newly emerged mutations for HA (hemagglutinin) in 2018 are revealed (i.e., S183P and R221K). Intriguingly, the substitution R221K falls into the RBS (receptor binding site) of HA protein, which could affect antigenic properties of influenza A(H1N1)pdm09 viruses, and another substitution S183P near to RBS with a high covering frequency (11/14 strains) in 2018 is exactly located at the epitope B. Notably, the NA (neuraminidase) protein harbors a new mutation I23T, potentially involved in N-glycosylation. Based on the background with a higher evolutionary rate in 2018 strains, we deeply evaluate the potential vaccine efficacy against Lincang strains and discover a substantive decline of the vaccine efficacy in 2018. Our analyses reaffirm that the real-time molecular surveillance and timely updated vaccine strains for prevention and control of influenza A(H1N1)pdm09 are crucial in the future.


Assuntos
Evolução Molecular , Vírus da Influenza A Subtipo H1N1/genética , Sequenciamento Completo do Genoma , Sequência de Aminoácidos , China , Análise Mutacional de DNA , Demografia , Epitopos/química , Glicoproteínas de Hemaglutininação de Vírus da Influenza/genética , Humanos , Vacinas contra Influenza/imunologia , Mutação/genética , Neuraminidase/genética , Filogenia , Resultado do Tratamento
17.
Cell Host Microbe ; 27(5): 695-698, 2020 05 13.
Artigo em Inglês | MEDLINE | ID: covidwho-245700

RESUMO

As scientists consider SARS-CoV-2 vaccine design, we discuss problems that may be encountered and how to tackle them by what we term "rational vaccine design." We further discuss approaches to pan-coronavirus vaccines. We draw on experiences from recent research on several viruses including HIV and influenza, as well as coronaviruses.


Assuntos
Anticorpos Antivirais/imunologia , Antígenos Virais/imunologia , Betacoronavirus/imunologia , Infecções por Coronavirus/prevenção & controle , Pandemias/prevenção & controle , Pneumonia Viral/prevenção & controle , Vacinas Virais/imunologia , Vacinas contra a AIDS/imunologia , Vacinas contra a AIDS/normas , Infecções por Coronavirus/imunologia , Humanos , Vacinas contra Influenza/imunologia , Vacinas contra Influenza/normas , Pneumonia Viral/imunologia , Projetos de Pesquisa/tendências
18.
Viruses ; 12(5)2020 05 08.
Artigo em Inglês | MEDLINE | ID: covidwho-209967

RESUMO

In the midst of the ongoing COVID-19 coronavirus pandemic, influenza virus remains a major threat to public health due to its potential to cause epidemics and pandemics with significant human mortality. Cases of H7N9 human infections emerged in eastern China in 2013 and immediately raised pandemic concerns as historically, pandemics were caused by the introduction of new subtypes into immunologically naïve human populations. Highly pathogenic H7N9 cases with severe disease were reported recently, indicating the continuing public health threat and the need for a prophylactic vaccine. Here we review the development of recombinant influenza virus-like particles (VLPs) as vaccines against H7N9 virus. Several approaches to vaccine development are reviewed including the expression of VLPs in mammalian, plant and insect cell expression systems. Although considerable progress has been achieved, including demonstration of safety and immunogenicity of H7N9 VLPs in the human clinical trials, the remaining challenges need to be addressed. These challenges include improvements to the manufacturing processes, as well as enhancements to immunogenicity in order to elicit protective immunity to multiple variants and subtypes of influenza virus.


Assuntos
Subtipo H7N9 do Vírus da Influenza A/imunologia , Vacinas contra Influenza/imunologia , Vacinas de Partículas Semelhantes a Vírus/genética , Animais , Antígenos Virais/imunologia , Ensaios Clínicos como Assunto , Epitopos , Antígenos de Histocompatibilidade Classe II , Humanos
19.
F1000Res ; 92020.
Artigo em Inglês | MEDLINE | ID: mdl-32399192

RESUMO

Seasonal influenza remains a major public health problem, responsible for hundreds of thousands of deaths every year, mostly of elderly people. Despite the wide availability of vaccines, there are multiple problems decreasing the effectiveness of vaccination programs. These include viral variability and hence the requirement to match strains by estimating which will become prevalent each season, problems associated with vaccine and adjuvant production, and the route of administration as well as the perceived lower vaccine efficiency in older adults. Clinical protection is still suboptimal for all of these reasons, and vaccine uptake remains too low in most countries. Efforts to improve the effectiveness of influenza vaccines include developing universal vaccines independent of the circulating strains in any particular season and stimulating cellular as well as humoral responses, especially in the elderly. This commentary assesses progress over the last 3 years towards achieving these aims. Since the beginning of 2020, an unprecedented international academic and industrial effort to develop effective vaccines against the new coronavirus SARS-CoV-2 has diverted attention away from influenza, but many of the lessons learned for the one will synergize with the other to mutual advantage. And, unlike the SARS-1 epidemic and, we hope, the SARS-CoV-2 pandemic, influenza will not be eliminated and thus efforts to improve influenza vaccines will remain of crucial importance.


Assuntos
Vacinas contra Influenza/imunologia , Influenza Humana/prevenção & controle , Betacoronavirus , Infecções por Coronavirus , Humanos , Pandemias , Pneumonia Viral
20.
Viruses ; 12(5)2020 05 08.
Artigo em Inglês | MEDLINE | ID: mdl-32397182

RESUMO

In the midst of the ongoing COVID-19 coronavirus pandemic, influenza virus remains a major threat to public health due to its potential to cause epidemics and pandemics with significant human mortality. Cases of H7N9 human infections emerged in eastern China in 2013 and immediately raised pandemic concerns as historically, pandemics were caused by the introduction of new subtypes into immunologically naïve human populations. Highly pathogenic H7N9 cases with severe disease were reported recently, indicating the continuing public health threat and the need for a prophylactic vaccine. Here we review the development of recombinant influenza virus-like particles (VLPs) as vaccines against H7N9 virus. Several approaches to vaccine development are reviewed including the expression of VLPs in mammalian, plant and insect cell expression systems. Although considerable progress has been achieved, including demonstration of safety and immunogenicity of H7N9 VLPs in the human clinical trials, the remaining challenges need to be addressed. These challenges include improvements to the manufacturing processes, as well as enhancements to immunogenicity in order to elicit protective immunity to multiple variants and subtypes of influenza virus.


Assuntos
Subtipo H7N9 do Vírus da Influenza A/imunologia , Vacinas contra Influenza/imunologia , Vacinas de Partículas Semelhantes a Vírus/genética , Animais , Antígenos Virais/imunologia , Ensaios Clínicos como Assunto , Epitopos , Antígenos de Histocompatibilidade Classe II , Humanos
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