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1.
Vaccine ; 41(2): 304-314, 2023 Jan 09.
Artigo em Inglês | MEDLINE | ID: mdl-36587961

RESUMO

All seasonal influenza vaccines for 2021-2022 in the US were quadrivalent and the market continues to be dominated by intramuscular delivery of non-adjuvanted, virion-derived antigens grown in chicken eggs. Up to four new egg-adapted production influenza vaccine strains must be generated each year. The introduction in 2012 of Flucelvax®, which is grown in mammalian suspension cell culture and uses vaccine production strains without adaptive mutations for efficient growth in eggs, represented a major advance in vaccine production technology. Here we demonstrate that Flucelvax can be reformulated and combined with a liposomal adjuvant containing QS-21 (Verndari Adjuvant System 1.1, VAS1.1) or QS-21 and 3D-PHAD (VAS1.2) for intradermal administration using a painless skin patch, VaxiPatch™. VAS1.2 is similar to AS01B, the adjuvant system used in Shingrix® and Mosquirix™. We show that Flucelvax, when reformulated and concentrated using tangential flow filtration (TFF), maintains hemagglutination and single radial immunodiffusion (SRID) potency. Loading the reformulated Flucelvax material onto VaxiPatch arrays conferred high levels of resistance to heat stress and room temperature stability. TFF enriched vaccine antigens were combined with VAS1.1 or VAS1.2 and dispensed in 10nL drops into the pockets of 36 (total 360 nL) stainless steel microneedles arranged in a microarray 1.2 cm in diameter. Using VaxiPatch delivery of 2 µg of antigen, we demonstrated intramusuclar-comparable IgG and hemagglutination inhibition (HAI) immune responses in Sprague Dawley® rats. With addition of VAS1.2, antigen-specific IgG titers were increased as much as 68-fold (47-fold for VAS1.1) with improvements in seroconversion for three of four strains (all four were improved by VAS1.1). TFF-reformulated antigens combined with VAS1.1 or VAS1.2 and delivered by VaxiPatch showed only minor skin reactogenicity after 1 h and no skin reactogenicity after 24 h. These data indicate that VaxiPatch and the VAS system have the potential to be transformative for vaccine delivery.


Assuntos
Vacinas contra Influenza , Influenza Humana , Ratos , Animais , Humanos , Estações do Ano , Ratos Sprague-Dawley , Influenza Humana/prevenção & controle , Adjuvantes Imunológicos , Vacinação , Testes de Inibição da Hemaglutinação , Vacinas Combinadas , Anticorpos Antivirais , Imunoglobulina G , Injeções Intradérmicas , Mamíferos
3.
Sci Rep ; 13(1): 715, 2023 Jan 13.
Artigo em Inglês | MEDLINE | ID: mdl-36639569

RESUMO

Influenza A virus (IAV) is a leading cause of respiratory disease worldwide often resulting in severe morbidity and mortality. We have previously shown that the Bacterial Enzymatic Combinatorial Chemistry (BECC) adjuvants, BECC438 and BECC470, formulated with an influenza virus hemagglutinin (HA) protein vaccine, offer greater protection from influenza virus challenge in mouse respiratory models using adult mice than standard HA:adjuvant combinations. In this study, we determined that immunization with HA + BECC adjuvants also significantly broadened the epitopes targeted on HA as compared with other adjuvants, resulting in increased titers of antibodies directed against the highly conserved HA stalk domain. Importantly, we demonstrate that BECC470 combined with an influenza virus HA protein antigen in a prime-only immunization regimen was able to achieve complete protection from challenge in a ~ 12-month-old mouse aged model. Together, this demonstrates the heightened protection provided by the BECC470 adjuvant in an influenza virus vaccine model and shows the enhanced immune response, as compared to other adjuvants elicited by the formulation of HA with BECC470.


Assuntos
Vírus da Influenza A Subtipo H1N1 , Vacinas contra Influenza , Infecções por Orthomyxoviridae , Animais , Humanos , Camundongos , Adjuvantes Imunológicos , Anticorpos Antivirais , Glicoproteínas de Hemaglutininação de Vírus da Influenza , Hemaglutininas , Influenza Humana , Camundongos Endogâmicos BALB C , Receptor 4 Toll-Like
4.
Cell Host Microbe ; 31(1): 146-157, 2023 01 11.
Artigo em Inglês | MEDLINE | ID: mdl-36634620

RESUMO

Viruses that replicate in the human respiratory mucosa without infecting systemically, including influenza A, SARS-CoV-2, endemic coronaviruses, RSV, and many other "common cold" viruses, cause significant mortality and morbidity and are important public health concerns. Because these viruses generally do not elicit complete and durable protective immunity by themselves, they have not to date been effectively controlled by licensed or experimental vaccines. In this review, we examine challenges that have impeded development of effective mucosal respiratory vaccines, emphasizing that all of these viruses replicate extremely rapidly in the surface epithelium and are quickly transmitted to other hosts, within a narrow window of time before adaptive immune responses are fully marshaled. We discuss possible approaches to developing next-generation vaccines against these viruses, in consideration of several variables such as vaccine antigen configuration, dose and adjuventation, route and timing of vaccination, vaccine boosting, adjunctive therapies, and options for public health vaccination polices.


Assuntos
COVID-19 , Vacinas contra Influenza , Influenza Humana , Orthomyxoviridae , Humanos , COVID-19/prevenção & controle , SARS-CoV-2/genética , Anticorpos Antivirais
5.
Viruses ; 15(1)2023 Jan 09.
Artigo em Inglês | MEDLINE | ID: mdl-36680224

RESUMO

The influenza neuraminidase (NA) is a promising target for next-generation vaccines. Protection induced by vaccination with the computationally optimized broadly reactive NA antigen (N1-I COBRA NA) was characterized in both influenza serologically naive and pre-immune ferret models following H1N1 (A/California/07/2009, CA/09) or H5N1 (A/Vietnam/1203/2004, Viet/04) influenza challenges. The N1-I COBRA NA vaccine elicited antibodies with neutralizing ELLA activity against both seasonal and pandemic H1N1 influenza, as well as the H5N1 influenza virus. In both models, N1-I COBRA NA-vaccinated ferrets that were challenged with CA/09 virus had similar morbidity (weight loss and clinical symptoms) as ferrets vaccinated with the CA/09 HA control vaccine. There were significantly reduced viral titers compared to the mock-vaccinated control animals. Ferrets vaccinated with N1-I COBRA NA or Viet/04 NA vaccines were protected against the H5N1 virus infection with minimal clinical symptoms and negligible weight loss. In contrast, ferrets vaccinated with the CA/09 NA vaccine lost ~10% of their original body weight with 25% mortality. Vaccination with either HA or NA vaccines did not inhibit contact transmission of CA/09 virus to naïve cage mates. Overall, the N1-I COBRA vaccine elicited protective immune responses against both H1N1 and H5N1 infections and partially mitigated disease in contact-transmission receiving ferrets. These results indicate that the N1-I COBRA NA performed similarly to the CA/09 HA and NA positive controls. Therefore, the N1-I COBRA NA alone induces protection against viruses from both H5N1 and H1N1 subtypes, indicating its value as a vaccine component in broadly protective influenza vaccines.


Assuntos
Vírus da Influenza A Subtipo H1N1 , Virus da Influenza A Subtipo H5N1 , Vacinas contra Influenza , Infecções por Orthomyxoviridae , Animais , Anticorpos Antivirais , Furões , Glicoproteínas de Hemaglutininação de Vírus da Influenza , Vacinas contra Influenza/imunologia , Neuraminidase , Infecções por Orthomyxoviridae/prevenção & controle
6.
MMWR Morb Mortal Wkly Rep ; 72(3): 49-54, 2023 Jan 20.
Artigo em Inglês | MEDLINE | ID: mdl-36656786

RESUMO

Influenza seasons typically begin in October and peak between December and February (1); however, the 2022-23 influenza season in Tennessee began in late September and was characterized by high pediatric hospitalization rates during November. This report describes a field investigation conducted in Tennessee during November 2022, following reports of increasing influenza hospitalizations. Data from surveillance networks, patient surveys, and whole genome sequencing of influenza virus specimens were analyzed to assess influenza activity and secondary illness risk. Influenza activity increased earlier than usual among all age groups, and rates of influenza-associated hospitalization among children were high in November, reaching 12.6 per 100,000 in children aged <5 years, comparable to peak levels typically seen in high-severity seasons. Circulating influenza viruses were genetically similar to vaccine components. Among persons who received testing for influenza at outpatient clinics, children were twice as likely to receive a positive influenza test result as were adults. Among household contacts exposed to someone with influenza, children were more than twice as likely to become ill compared with adults. As the influenza season continues, it is important for all persons, especially those at higher risk for severe disease, to protect themselves from influenza. To prevent influenza and severe influenza complications, all persons aged ≥6 months should get vaccinated, avoid contact with ill persons, and take influenza antivirals if recommended and prescribed.


Assuntos
Vacinas contra Influenza , Influenza Humana , Adulto , Criança , Humanos , Lactente , Influenza Humana/prevenção & controle , Estações do Ano , Tennessee/epidemiologia , Vírus da Influenza B/genética , Vacinação
7.
Sci Rep ; 13(1): 1174, 2023 Jan 20.
Artigo em Inglês | MEDLINE | ID: mdl-36670200

RESUMO

Post-vaccination cytokine levels from 256 young adults who subsequently suffered breakthrough influenza infections were compared with matched controls. Modulation within the immune system is important for eliciting a protective response, and the optimal response differs according to vaccine formulation and delivery. For both inactivated influenza vaccine (IIV) and live attenuated influenza vaccines (LAIV) lower levels of IL-8 were observed in post-vaccination sera. Post-vaccination antibody levels were higher and IFN-γ levels were lower in IIV sera compared to LAIV sera. Subjects who suffered breakthrough infections after IIV vaccination had higher levels of sCD25 compared to the control group. There were differences in LAIV post-vaccination interleukin levels for subjects who subsequently suffered breakthrough infections, but these differences were masked in subjects who received concomitant vaccines. Wide variances, sex-based differences and confounders such as concomitant vaccines thwart the establishment of specific cytokine responses as a correlate of protection, but our results provide real world evidence that the status of the immune system following vaccination is important for successful vaccination and subsequent protection against disease.


Assuntos
Vacinas contra Influenza , Influenza Humana , Adulto Jovem , Humanos , Influenza Humana/prevenção & controle , Citocinas , Vacinação/métodos , Vacinas Atenuadas , Vacinas de Produtos Inativados , Anticorpos Antivirais
8.
Viruses ; 15(1)2023 Jan 10.
Artigo em Inglês | MEDLINE | ID: mdl-36680239

RESUMO

Neuraminidase (NA) is an important surface protein on influenza virions, playing an essential role in the viral life cycle and being a key target of the immune system. Despite the importance of NA-based immunity, current vaccines are focused on the hemagglutinin (HA) protein as the target for protective antibodies, and the amount of NA is not standardized in virion-based vaccines. Antibodies targeting NA are predominantly protective, reducing infection severity and viral shedding. Recently, NA-specific monoclonal antibodies have been characterized, and their target epitopes have been identified. This review summarizes the characteristics of NA, NA-specific antibodies, the mechanism of NA inhibition, and the recent efforts towards developing NA-based and NA-incorporating influenza vaccines.


Assuntos
Vacinas contra Influenza , Influenza Humana , Infecções por Orthomyxoviridae , Humanos , Neuraminidase , Anticorpos Monoclonais , Anticorpos Antivirais , Influenza Humana/prevenção & controle , Glicoproteínas de Hemaglutininação de Vírus da Influenza
9.
Viruses ; 15(1)2023 Jan 11.
Artigo em Inglês | MEDLINE | ID: mdl-36680243

RESUMO

Initial exposure to influenza virus(es) during early childhood produces protective antibodies that may be recalled following future exposure to subsequent viral infections or vaccinations. Most influenza vaccine research studies use immunologically naïve animal models to assess vaccine effectiveness. However, most people have an extensive influenza immune history, with memory cells produced by viruses or vaccines representing multiple influenza viruses. In this study, we explored the effect influenza seasonal virus-induced immunity has on pre-pandemic influenza virus vaccination. The mice that were pre-immune to historical H1N1 and H3N2 seasonal influenza viruses were vaccinated with adjuvanted pre-pandemic (H2, H5, and H7) HA-based computationally optimized broadly reactive antigen (COBRA) vaccines, and were fully protected from lethal challenge, whereas the mock-vaccinated mice, with or without pre-immunity, were not protected from morbidity or mortality. Detectable antibody titers were present in the pre-immune mice vaccinated with a single dose of vaccine, but not in the immunologically naïve mice. The mice vaccinated twice with the trivalent COBRA HA vaccine had similar antibody titers regardless of their pre-immune status. Overall, seasonal pre-immunity did not interfere with the immune responses elicited by pre-pandemic COBRA HA vaccines or the protection against pre-pandemic viruses.


Assuntos
Vírus da Influenza A Subtipo H1N1 , Vacinas contra Influenza , Influenza Humana , Infecções por Orthomyxoviridae , Vacinas de Partículas Semelhantes a Vírus , Pré-Escolar , Humanos , Animais , Camundongos , Vírus da Influenza A Subtipo H3N2 , Anticorpos Antivirais , Glicoproteínas de Hemaglutininação de Vírus da Influenza
10.
Viruses ; 15(1)2023 Jan 14.
Artigo em Inglês | MEDLINE | ID: mdl-36680282

RESUMO

Influenza represents a major and ongoing public health hazard. Current collaborative efforts are aimed toward creating a universal flu vaccine with the goals of both improving responses to vaccination and increasing the breadth of protection against multiple strains and clades from a single vaccine. As an intermediate step toward these goals, the current work is focused on evaluating the systemic host response to vaccination in both normal and high-risk populations, such as the obese and geriatric populations, which have been linked to poor responses to vaccination. We therefore employed a metabolomics approach using a time-course (n = 5 time points) of the response to human vaccination against influenza from the time before vaccination (pre) to 90 days following vaccination. We analyzed the urinary profiles of a cohort of subjects (n = 179) designed to evenly sample across age, sex, BMI, and other demographic factors, stratifying their responses to vaccination as "High", "Low", or "None" based on the seroconversion measured by hemagglutination inhibition assay (HAI) from plasma samples at day 28 post-vaccination. Overall, we putatively identified 15,903 distinct, named, small-molecule structures (4473 at 10% FDR) among the 895 samples analyzed, with the aim of identifying metabolite correlates of the vaccine response, as well as prognostic and diagnostic markers from the periods before and after vaccination, respectively. Notably, we found that the metabolic profiles could unbiasedly separate the high-risk High-responders from the high-risk None-responders (obese/geriatric) within 3 days post-vaccination. The purine metabolites Guanine and Hypoxanthine were negatively associated with high seroconversion (p = 0.0032, p < 0.0001, respectively), while Acetyl-Leucine and 5-Aminovaleric acid were positively associated. Further changes in Cystine, Glutamic acid, Kynurenine and other metabolites implicated early oxidative stress (3 days) after vaccination as a hallmark of the High-responders. Ongoing efforts are aimed toward validating these putative markers using a ferret model of influenza infection, as well as an independent cohort of human seasonal vaccination and human challenge studies with live virus.


Assuntos
Vacinas contra Influenza , Influenza Humana , Humanos , Animais , Idoso , Anticorpos Antivirais , Furões , Vacinação , Testes de Inibição da Hemaglutinação , Metaboloma
11.
BMC Public Health ; 23(1): 143, 2023 Jan 20.
Artigo em Inglês | MEDLINE | ID: mdl-36670376

RESUMO

BACKGROUND: The UK is rolling out a national childhood influenza immunisation programme for children, delivered through primary care and schools. Behaviourally-informed letters and reminders have been successful at increasing uptake of other public health interventions. Therefore, we investigated the effects of a behaviourally-informed letter on uptake of the vaccine at GP practices, and of a letter and a reminder (SMS/ email) on uptake at schools. METHODS AND RESULTS: Study 1 was a cluster-randomised parallel trial of 21,786 two- and three-year olds in 250 GP practices, conducted during flu season (September to January inclusive) 2016/7. The intervention was a centrally-sent behaviourally-informed invitation letter, control was usual care. The proportion of two- and three-year olds in each practice who received a vaccination by 31st January 2017 was 23.4% in the control group compared to 37.1% in the intervention group (OR = 1.93; 95% CI = 1.82, 2.05, p <  0.001). Study 2 was a 2 (behavioural letter vs standard letter) × 2 (reminder vs no reminder) factorial trial of 1108 primary schools which included 3010 school years 1-3. Letters were sent to parents from providers, and reminders sent to parents from the schools. In the standard-letter-no-reminder arm, an average of 61.6% of eligible children in each school year were vaccinated, compared to 61.9% in the behavioural-letter-no-reminder arm, 63.5% in the standard-letter-plus-reminder arm, and 62.9% in the behavioural-letter-plus reminder condition, F(3, 2990) = 2.68, p = 0.046. In a multi-level model, with demographic variables as fixed effects, the proportion of eligible students in the school year who were vaccinated increased with the reminder, ß = 0.086 (0.041), p <  0.036, but there was no effect of the letter nor any interaction effect. CONCLUSION: Sending a behaviourally informed invitation letter can increase uptake of childhood influenza vaccines at the GP surgery compared to usual practice. A reminder SMS or email can increase uptake of the influenza vaccine in schools, but the effect size was minimal. TRIAL REGISTRATION: Study 1: Trial registration: ClinicalTrials.gov Identifier: NCT02921633. Study 2: Trial registration: ClinicalTrials.gov Identifier: NCT02883972.


Assuntos
Vacinas contra Influenza , Influenza Humana , Envio de Mensagens de Texto , Criança , Humanos , Influenza Humana/prevenção & controle , Sistemas de Alerta , Instituições Acadêmicas , Vacinação
12.
Br J Gen Pract ; 73(727): e148-e155, 2023 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-36702602

RESUMO

BACKGROUND: Pregnant women are at increased risk from influenza, yet maternal influenza vaccination levels remain suboptimal. AIM: To estimate associations between sociodemographic and health characteristics and seasonal influenza vaccination uptake among pregnant women, and to understand trends over time to inform interventions to improve vaccine coverage. DESIGN AND SETTING: Retrospective cohort study using linked electronic health records of women in North West London with a pregnancy overlapping an influenza season between September 2010 and February 2020. METHOD: A multivariable mixed-effects logistic regression model was used to identify associations between characteristics of interest and the primary outcome of influenza vaccination. RESULTS: In total, 451 954 pregnancies, among 260 744 women, were included. In 85 376 (18.9%) pregnancies women were vaccinated against seasonal influenza. Uptake increased from 8.4% in 2010/11 to 26.4% in 2017/18, dropping again to 21.1% in 2019/20. Uptake was lowest among women aged 15-19 years (11.9%; reference category) or ≥40 years (15.2%; odds ratio [OR] 1.17, 95% confidence interval [CI] = 1.10 to 1.24); of Black (14.1%; OR 0.55, 95% CI = 0.53 to 0.57) or unknown ethnicity (9.9%; OR 0.42, 95% CI = 0.39 to 0.46); who lived in more deprived areas (OR least versus most deprived [reference category] 1.16, 95% CI = 1.11 to 1.21); or with no known risk factors for severe influenza. CONCLUSION: Seasonal influenza vaccine uptake in pregnant women increased in the decade before the COVID-19 pandemic, but remained suboptimal. Targeted approaches are recommended to reducing inequalities in access to vaccination and should focus on women of Black ethnicity, younger and older women, and women living in deprived areas.


Assuntos
COVID-19 , Vacinas contra Influenza , Influenza Humana , Complicações Infecciosas na Gravidez , Feminino , Gravidez , Humanos , Idoso , Influenza Humana/epidemiologia , Influenza Humana/prevenção & controle , Complicações Infecciosas na Gravidez/epidemiologia , Complicações Infecciosas na Gravidez/prevenção & controle , Estudos Retrospectivos , Pandemias , Vacinas contra Influenza/uso terapêutico , Vacinação
13.
Immun Inflamm Dis ; 11(1): e759, 2023 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-36705404

RESUMO

INTRODUCTION: Influenza or SARS-CoV-2 vaccination is especially recommended for people with underlying diseases. For the large number of patients with chronic hepatitis B virus infection (CHB), studies on their immune responses to these vaccines are still lacking. METHODS: A total of 57 CHB patients and 19 healthy controls (HCs) receiving inactivated influenza vaccination were prospectively followed up. Influenza-specific immunoglobulin G (IgG) antibodies (anti-H1N1, anti-H3N2, and anti-B IgG), antibody-secreting cells (ASCs), and circulating T follicular helper cells were assessed simultaneously. Eight CHB patients subsequently got inactivated SARS-CoV-2 vaccination during 1-year follow-up, and levels of serum antibodies against SARS-CoV-2 were further analyzed. RESULTS: On day 28 after influenza vaccination, three influenza antibodies levels appeared to be lower in CHB patients than in HCs. And anti-H1N1 IgG level was significantly decreased in cirrhotic patients (p < .05). Anti-H1N1 IgG levels (day 28) were positively correlated with ASC frequencies (day 7) (p < .05), and negatively correlated with cirrhosis and hepatitis B surface antigen levels (p < .05). Anti-SARS-CoV-2 antibodies were higher in patients with influenza vaccination history than in patients without the history (p < .05). Moreover, positive correlations existed between influenza vaccination history and anti-SARS-CoV-2 antibody levels (p < .01). CONCLUSIONS: CHB patients, especially those with cirrhosis, appeared to have a decreased antibody response to inactivated influenza vaccine. A history of inactivated influenza vaccination within 1 year before inactivated SARS-CoV-2 vaccination might induce stronger anti-SARS-CoV-2 antibody response.


Assuntos
COVID-19 , Hepatite B Crônica , Vacinas contra Influenza , Influenza Humana , Humanos , Influenza Humana/prevenção & controle , Vacinas contra COVID-19 , Formação de Anticorpos , COVID-19/prevenção & controle , SARS-CoV-2 , Vacinação , Anticorpos Antivirais , Vacinas de Produtos Inativados , Imunoglobulina G
14.
Influenza Other Respir Viruses ; 17(1): e13069, 2023 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-36702797

RESUMO

BACKGROUND: In 2021-2022, influenza A viruses dominated in Europe. The I-MOVE primary care network conducted a multicentre test-negative study to measure influenza vaccine effectiveness (VE). METHODS: Primary care practitioners collected information on patients presenting with acute respiratory infection. Cases were influenza A(H3N2) or A(H1N1)pdm09 RT-PCR positive, and controls were influenza virus negative. We calculated VE using logistic regression, adjusting for study site, age, sex, onset date, and presence of chronic conditions. RESULTS: Between week 40 2021 and week 20 2022, we included over 11 000 patients of whom 253 and 1595 were positive for influenza A(H1N1)pdm09 and A(H3N2), respectively. Overall VE against influenza A(H1N1)pdm09 was 75% (95% CI: 43-89) and 81% (95% CI: 45-93) among those aged 15-64 years. Overall VE against influenza A(H3N2) was 29% (95% CI: 12-42) and 25% (95% CI: -41 to 61), 33% (95% CI: 14-49), and 26% (95% CI: -22 to 55) among those aged 0-14, 15-64, and over 65 years, respectively. The A(H3N2) VE among the influenza vaccination target group was 20% (95% CI: -6 to 39). All 53 sequenced A(H1N1)pdm09 viruses belonged to clade 6B.1A.5a.1. Among 410 sequenced influenza A(H3N2) viruses, all but eight belonged to clade 3C.2a1b.2a.2. DISCUSSION: Despite antigenic mismatch between vaccine and circulating strains for influenza A(H3N2) and A(H1N1)pdm09, 2021-2022 VE estimates against circulating influenza A(H1N1)pdm09 were the highest within the I-MOVE network since the 2009 influenza pandemic. VE against A(H3N2) was lower than A(H1N1)pdm09, but at least one in five individuals vaccinated against influenza were protected against presentation to primary care with laboratory-confirmed influenza.


Assuntos
Vírus da Influenza A Subtipo H1N1 , Vacinas contra Influenza , Influenza Humana , Humanos , Estudos de Casos e Controles , Europa (Continente)/epidemiologia , Vírus da Influenza A Subtipo H3N2/genética , Influenza Humana/epidemiologia , Influenza Humana/prevenção & controle , Atenção Primária à Saúde , Vacinação , Eficácia de Vacinas , Masculino , Feminino , Recém-Nascido , Lactente , Pré-Escolar , Criança , Adolescente , Adulto Jovem , Adulto , Pessoa de Meia-Idade , Idoso
15.
Sci Adv ; 9(4): eade2708, 2023 Jan 27.
Artigo em Inglês | MEDLINE | ID: mdl-36706192

RESUMO

Membrane proteins expressed on the surface of enveloped viruses are conformational antigens readily recognized by B cells of the immune system. An effective vaccine would require the synthesis and delivery of these native conformational antigens in lipid membranes that preserve specific epitope structures. We have created an extracellular vesicle-based technology that allows viral membrane antigens to be selectively recruited onto the surface of WW domain-activated extracellular vesicles (WAEVs). Budding of WAEVs requires secretory carrier-associated membrane protein 3, which through its proline-proline-alanine-tyrosine motif interacts with WW domains to recruit fused viral membrane antigens onto WAEVs. Immunization with influenza and HIV viral membrane proteins displayed on WAEVs elicits production of virus-specific neutralizing antibodies and, in the case of influenza antigens, protects mice from the lethal viral infection. WAEVs thus represent a versatile platform for presenting and delivering membrane antigens as vaccines against influenza, HIV, and potentially many other viral pathogens.


Assuntos
Vesículas Extracelulares , Infecções por HIV , Vacinas contra Influenza , Influenza Humana , Animais , Camundongos , Humanos , Antígenos Virais , Domínios WW , Antígenos , Prolina
17.
PLoS One ; 18(1): e0280811, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36662890

RESUMO

Manufactured influenza vaccines have to contain a defined amount of hemagglutinin (HA) antigen. Therefore, vaccine viruses with a high HA antigen yield (HAY) are preferable for manufacturing vaccines, particularly vaccines in response to a pandemic, when vaccines need to be rapidly produced. However, the viral properties associated with a high HAY have not yet been fully clarified. To identify the HAY-associated traits, we first propagated 26 H5 candidate vaccine viruses (CVVs) in eggs, which were previously developed based on genetic reassortment methods using master viruses, to determine their total protein yield (TPY), ratio of HA to total viral protein (%-HA content) and HAY. The results revealed that the HAY was correlated with the TPY but not with the %-HA content. We further found that altering the sequences of the 3' noncoding region of HA vRNA or replacing the master virus improved the HAYs and TPYs of the low-HAY CVVs to approximately double the values of the original CVVs but did not change the %-HA content, which a previous study suggested was associated with the HAY. Analyses based on real-time PCR assays and scanning electron microscopy revealed that the virus samples with an improved HAY contained more copies of the virus genome and viral particles than the original samples. The results suggest that an improvement in virus growth (i.e., an increase in the amount of viral particles) leads to an increase in the TPY and thus in the HAY, regardless of the %-HA content. The approximately twofold increase in the HAY shown in this study may not appear to represent a large improvement, but the impact will be significant given the millions of chicken eggs used to produce vaccines. These findings will be informative for developing high-HAY vaccine viruses.


Assuntos
Vacinas contra Influenza , Orthomyxoviridae , Animais , Hemaglutininas/genética , Glicoproteínas de Hemaglutininação de Vírus da Influenza , Galinhas , Anticorpos Antivirais
18.
BMC Public Health ; 23(1): 91, 2023 Jan 12.
Artigo em Inglês | MEDLINE | ID: mdl-36635715

RESUMO

BACKGROUND: The elderly bear the highest burden of South Africa's estimated annual > 10 million influenza cases and > 11,000 influenza-related deaths. Unvaccinated healthcare workers (HCWs) are at high occupational risk of contracting influenza, and may transmit influenza to elderly patients in their care. Thus, the South African National Department of Health recommends that HCWs receive annual influenza vaccination. This study aimed to determine influenza vaccination coverage among HCWs; identify reasons for their vaccination status; and investigate if HCWs recommend vaccination to their elderly patients. METHODS: A descriptive study was conducted in 18 community health centres and 44 private sector and non-governmental organisation managed old age homes across South Africa, using a self-administered structured questionnaire, which was distributed to 360 HCWs present on the day of data collection. Data were captured using Microsoft Excel® and imported to Epi Info™ 7 (Centers for Disease Control and Prevention, USA) for descriptive statistical analysis. Ethics approval (SMUREC/P/36/2018: PG) and permission to conduct the study at the facilities were obtained. All participants provided informed consent. RESULTS: The response rate was 76.7% (276/360). Most participants were female (90.9% [251/276]), nursing professionals (81.2% [224/276]) with a mean age of 41.1 ± 11.7 years. Although 62.7% of participants indicated having ever received at least one dose of the influenza vaccine, influenza vaccine uptake for 2017 and 2018 was 24.36% (41/276) and 33.3% (92/276) respectively. The main reasons given for never being vaccinated against influenza were related to the unavailability of the vaccine (70.9%) and vaccine hesitancy (27.2%). Most participants (67.8% [187/276]) recommended vaccines to elderly patients in their care. CONCLUSION: The main reasons behind low influenza vaccine uptake by HCWs in South Africa who care for the elderly were related to unavailability of the vaccine and vaccine hesitancy. Strategies to educate HCWs on the importance of influenza vaccination, while concurrently increasing sustained and easy access to the vaccine by HCWs are needed to preserve public health.


Assuntos
Vacinas contra Influenza , Influenza Humana , Humanos , Feminino , Idoso , Adulto , Pessoa de Meia-Idade , Masculino , Vacinas contra Influenza/uso terapêutico , Influenza Humana/prevenção & controle , Instituição de Longa Permanência para Idosos , África do Sul , Vacinação , Inquéritos e Questionários , Pessoal de Saúde , Atenção Primária à Saúde , Atitude do Pessoal de Saúde
19.
Euro Surveill ; 28(3)2023 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-36695484

RESUMO

BackgroundPost-authorisation vaccine safety surveillance is well established for reporting common adverse events of interest (AEIs) following influenza vaccines, but not for COVID-19 vaccines.AimTo estimate the incidence of AEIs presenting to primary care following COVID-19 vaccination in England, and report safety profile differences between vaccine brands.MethodsWe used a self-controlled case series design to estimate relative incidence (RI) of AEIs reported to the national sentinel network, the Oxford-Royal College of General Practitioners Clinical Informatics Digital Hub. We compared AEIs (overall and by clinical category) 7 days pre- and post-vaccination to background levels between 1 October 2020 and 12 September 2021.ResultsWithin 7,952,861 records, 781,200 individuals (9.82%) presented to general practice with 1,482,273 AEIs, 4.85% within 7 days post-vaccination. Overall, medically attended AEIs decreased post-vaccination against background levels. There was a 3-7% decrease in incidence within 7 days after both doses of Comirnaty (RI: 0.93; 95% CI: 0.91-0.94 and RI: 0.96; 95% CI: 0.94-0.98, respectively) and Vaxzevria (RI: 0.97; 95% CI: 0.95-0.98). A 20% increase was observed after one dose of Spikevax (RI: 1.20; 95% CI: 1.00-1.44). Fewer AEIs were reported as age increased. Types of AEIs, e.g. increased neurological and psychiatric conditions, varied between brands following two doses of Comirnaty (RI: 1.41; 95% CI: 1.28-1.56) and Vaxzevria (RI: 1.07; 95% CI: 0.97-1.78).ConclusionCOVID-19 vaccines are associated with a small decrease in medically attended AEI incidence. Sentinel networks could routinely report common AEI rates, contributing to reporting vaccine safety.


Assuntos
Vacinas contra COVID-19 , COVID-19 , Vacinas contra Influenza , Humanos , Vacina BNT162 , ChAdOx1 nCoV-19 , COVID-19/epidemiologia , COVID-19/prevenção & controle , Vacinas contra COVID-19/efeitos adversos , Inglaterra/epidemiologia , Vacinas contra Influenza/efeitos adversos , Vacinação/efeitos adversos
20.
Health Promot Int ; 38(1)2023 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-36617290

RESUMO

There is a gap in understanding specific features of health literacy that might be associated with adherence to influenza immunization. The aim of this study was to examine the association of health literacy with avoidance of influenza immunization and beliefs about the influenza vaccine among people with chronic diseases. Selection of study participants was based on a case-control study design in a population of people with chronic illnesses living in the Foca region (Republic of Srpska, Bosnia and Herzegovina) and who were entitled to receive a free influenza shot in season 2017/2018. The cases represented all non-vaccinated people (a total of 146) and the controls were vaccinated people (a total of 149) matched according to town of residence. Participants were interviewed in person from April to December 2018 using a socio-demographic questionnaire, Health Literacy Questionnaire (HLQ) and Health Belief Model Applied to Influenza (HBMAI). Better score on 'Feeling understood and supported by healthcare providers', 'Social support for health' and 'Ability to actively engage with healthcare providers' was associated with more perceived benefits of influenza immunization in men, but not in women. Perceiving more Barriers to influenza immunization was associated with lower scores on 'Feeling understood and supported by healthcare providers', 'Have sufficient information to manage health', 'Social support for health' and 'Ability to actively engage with healthcare providers' in both men and women. Health literacy may be associated with the perception of susceptibility to influenza, benefits and barriers to influenza immunization and motivations to receive influenza vaccine.


We aimed to examine the association between health literacy with missing free influenza immunization. This research focused on people with chronic illnesses living in the Foca region (Republic of Srpska, Bosnia and Herzegovina) and who were entitled to receive a free influenza shot in season 2017/2018. All non-vaccinated people (cases) and corresponding number vaccinated people (controls) were included. People were interviewed using the socio-demographic questionnaire, Health Literacy Questionnaire (HLQ) and Health Belief Model Applied to Influenza (HBMAI). Mathematical model suggested potential difference between men and women, so the analyses were performed separately for each gender. People who had better health literacy were not more likely to receive the influenza vaccine. Men who felt better understood and supported by healthcare providers, who had more social support and were actively engaging with healthcare providers were more likely to perceive benefits of influenza immunization. People who felt less understood and supported by healthcare providers, who felt that they did not have sufficient information to manage health and social support and were not actively engaging with healthcare providers were more likely to perceive barriers to influenza immunization. People with chronic diseases should be encouraged to improve their health literacy to better understand influenza immunization.


Assuntos
Letramento em Saúde , Vacinas contra Influenza , Influenza Humana , Masculino , Humanos , Feminino , Influenza Humana/prevenção & controle , Estudos de Casos e Controles , Estudos Transversais , Doença Crônica , Vacinação , Inquéritos e Questionários
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