Postpandemic Sentinel Surveillance of Respiratory Diseases in the Context of the World Health Organization Mosaic Framework: Protocol for a Development and Evaluation Study Involving the English Primary Care Network 2023-2024.

BACKGROUND: Prepandemic sentinel surveillance focused on improved management of winter pressures, with influenza-like illness (ILI) being the key clinical indicator. The World Health Organization (WHO) global standards for influenza surveillance include monitoring acute respiratory infection (ARI) and ILI. The WHO's mosaic framework recommends that the surveillance strategies of countries include the virological monitoring of respiratory viruses with pandemic potential such as influenza. The Oxford-Royal College of General Practitioner Research and Surveillance Centre (RSC) in collaboration with the UK Health Security Agency (UKHSA) has provided sentinel surveillance since 1967, including virology since 1993. OBJECTIVE: We aim to describe the RSC's plans for sentinel surveillance in the 2023-2024 season and evaluate these plans against the WHO mosaic framework. METHODS: Our approach, which includes patient and public involvement, contributes to surveillance objectives across all 3 domains of the mosaic framework. We will generate an ARI phenotype to enable reporting of this indicator in addition to ILI. These data will support UKHSA's sentinel surveillance, including vaccine effectiveness and burden of disease studies. The panel of virology tests analyzed in UKHSA's reference laboratory will remain unchanged, with additional plans for point-of-care testing, pneumococcus testing, and asymptomatic screening. Our sampling framework for serological surveillance will provide greater representativeness and more samples from younger people. We will create a biomedical resource that enables linkage between clinical data held in the RSC and virology data, including sequencing data, held by the UKHSA. We describe the governance framework for the RSC. RESULTS: We are co-designing our communication about data sharing and sampling, contextualized by the mosaic framework, with national and general practice patient and public involvement groups. We present our ARI digital phenotype and the key data RSC network members are requested to include in computerized medical records. We will share data with the UKHSA to report vaccine effectiveness for COVID-19 and influenza, assess the disease burden of respiratory syncytial virus, and perform syndromic surveillance. Virological surveillance will include COVID-19, influenza, respiratory syncytial virus, and other common respiratory viruses. We plan to pilot point-of-care testing for group A streptococcus, urine tests for pneumococcus, and asymptomatic testing. We will integrate test requests and results with the laboratory-computerized medical record system. A biomedical resource will enable research linking clinical data to virology data. The legal basis for the RSC's pseudonymized data extract is The Health Service (Control of Patient Information) Regulations 2002, and all nonsurveillance uses require research ethics approval. CONCLUSIONS: The RSC extended its surveillance activities to meet more but not all of the mosaic framework's objectives. We have introduced an ARI indicator. We seek to expand our surveillance scope and could do more around transmissibility and the benefits and risks of nonvaccine therapies.

Estimates of Seasonal Influenza Burden That Could Be Averted by Improved Influenza Vaccines in the Australian Population Aged Under 65 Years, 2015-2019.

BACKGROUND: The interpretation of relative vaccine effectiveness (rVE) of improved influenza vaccines is complex. Estimation of burden averted is useful to contextualise their potential impact across different seasons. For the population aged under 65 years in Australia, this study estimated the additional morbidity and mortality that could be averted using improved influenza vaccines. METHODS: We used observed, season-specific (2015-2019) influenza notification and influenza-coded hospitalisation frequencies and published modelled estimates of influenza-associated hospitalisations and deaths that occurred under the prevailing influenza vaccination coverage scenario. After back-calculating to the estimated burden in the population without vaccination, we applied published standard influenza vaccine effectiveness and coverage estimates to calculate the burden potentially averted by standard and improved influenza vaccines. A plausible range of rVE values were used, assuming 50% coverage. RESULTS: The percentage point difference in absolute vaccine effectiveness (VE) of an improved vaccine compared to a standard vaccine is directly proportional to its rVE and inversely proportional to the effectiveness of the standard vaccine. The incremental burden averted by an improved vaccine is a function of both its difference in absolute VE and the severity of the influenza season. Assuming an rVE of 15% with 50% coverage, the improved vaccine was estimated to additionally avert 1517 to 12,641 influenza notifications, 287 to 1311 influenza-coded hospitalisations and 9 to 33 modelled all-cause influenza deaths per year compared to the standard vaccine. CONCLUSIONS: Improved vaccines can have substantial clinical and population impact, particularly when the effectiveness of standard vaccines is low, and burden is high.

Co-Administration of Influenza and COVID-19 Vaccines: A Cross-Sectional Survey of Canadian Adults' Knowledge, Attitudes, and Beliefs.

Vaccination rates against both influenza and COVID-19 fall short of targets, especially among persons at risk of influenza complications. To gain insights into strategies to boost influenza vaccine coverage, we surveyed 3000 Canadian residents aged ≥ 18 years and examined their knowledge and receipt of co-administered influenza and COVID-19 vaccines. During the 2022-2023 influenza season, 70% of respondents reported being aware the influenza and COVID-19 vaccines could be co-administered, but only 26.2% (95% CI, 23.6% to 28.8%) of respondents received them together. The most common reason for not getting the vaccines together was receipt of the COVID-19 vaccine before the annual influenza vaccine was available (reported by 34.5% [31.2% to 37.7%]). Lack of interest in co-administration was reported by 22.6% (20.8% to 24.3%); of this group, 20.8% (17.1% to 24.5%) reported seeing no benefit in receiving the two vaccines together and 17.2% (13.5% to 20.9%) were concerned about compounded adverse effects from the two vaccines. These results support the willingness of most Canadians to receive COVID-19 and influenza vaccines at the same time. Co-administration is a viable strategy to improve uptake of influenza vaccines, especially if health professionals proactively offer education and co-administration of influenza and COVID-19 (or other) vaccines as appropriate to clinical need.

Insights from Avian Influenza: A Review of Its Multifaceted Nature and Future Pandemic Preparedness.

Avian influenza viruses (AIVs) have posed a significant pandemic threat since their discovery. This review mainly focuses on the epidemiology, virology, pathogenesis, and treatments of avian influenza viruses. We delve into the global spread, past pandemics, clinical symptoms, severity, and immune response related to AIVs. The review also discusses various control measures, including antiviral drugs, vaccines, and potential future directions in influenza treatment and prevention. Lastly, by summarizing the insights from previous pandemic control, this review aims to direct effective strategies for managing future influenza pandemics.

Waning intra-season vaccine effectiveness against influenza A(H3N2) underlines the need for more durable protection.

BACKGROUND: The question of whether influenza vaccine effectiveness (VE) wanes over the winter season is still open and some contradictory findings have been reported. This study investigated the possible decline in protection provided by the available influenza vaccines. RESEARCH DESIGN AND METHODS: An individual-level pooled analysis of six test-negative case-control studies conducted in Italy between the 2018/2019 and 2022/2023 seasons was performed. Multivariable logistic regression analyses were performed to estimate weekly change in the odds of testing positive for influenza 14 days after vaccination. RESULTS: Of 6490 patients included, 1633 tested positive for influenza. Each week that had elapsed since vaccination was associated with an increase in the odds of testing positive for any influenza (4.9%; 95% CI: 2.0-8.0%) and for A(H3N2) (6.5%; 95% CI: 2.9-10.3%). This decline in VE was, however, significant only in children and older adults. A similar increase in the odds of testing positive was seen when the dataset was restricted to vaccinees only. Conversely, VE waning was less evident for A(H1N1)pdm09 or B strains. CONCLUSIONS: Significant waning of VE, especially against influenza A(H3N2), may be one of the factors associated with suboptimal end-of-season VE. Next-generation vaccines should provide more durable protection against A(H3N2).

Efectividad de la vacuna antigripal para prevenir casos graves de gripe. Temporada 2022/2023 / Effectiveness of influenza vaccine in preventing severe cases of influenza: Season 2022/2023

Introducción: La gripe supone una importante carga en términos de morbimortalidad, siendo la vacunación una de las medidas más efectivas para su prevención. Por lo que el objetivo de este estudio es conocer la efectividad de la vacuna antigripal para prevenir casos de gripe grave en los pacientes ingresados en un hospital de tercer nivel durante la temporada 2022/23. Metodología: Estudio de casos y controles. Se incluyeron todos los pacientes hospitalizados con resultado positivo en una RT-PCR de gripe. Se consideró caso a aquellos que cumplieron criterio de caso grave (neumonía, sepsis, fallo multiorgánico, ingreso en la UCI o exitus). Quienes no los cumplían se consideraron controles. Se calculó la efectividad vacunal (EV) para prevenir los casos graves y su intervalo de confianza al 95%. Resultados: Un total de 403 pacientes ingresaron con gripe confirmada. Noventa y ocho (24,3%) de ellos desarrollaron gripe grave. Del total, el 50,6% fueron varones y el 47,1% fueron mayores de 65 años. La EV ajustada por tipo de gripe, edad y ciertas comorbilidades fue del 40,6% (−21,9-71,1). En un análisis segmentado, la vacuna de la gripe resultó efectiva para la prevención de los casos graves en todas las categorías. Resultó especialmente relevante en el grupo de 65 años o más (EVa=60,9%; −2,0-85,0) y en los pacientes con gripe A (EVa=56,7%; 1,5-80,9). Conclusiones: La vacunación antigripal redujo notablemente la aparición de casos graves de gripe en los pacientes hospitalizados, por tanto, sigue siendo la principal estrategia para reducir la morbimortalidad y los costes asociados.(AU)

Introduction: Influenza poses a significant burden in terms of morbidity and mortality, with vaccination being one of the most effective measures for its prevention. Therefore, the aim of this study is to determine the effectiveness of the influenza vaccine in preventing cases of severe influenza in patients admitted to a tertiary hospital during the 2022/23 season. Methods: Case-control study. All hospitalised patients with a positive result in an RT-PCR for influenza were included. Those who met the criteria for a severe case (pneumonia, sepsis, multi-organ failure, admission to ICU or exitus) were considered cases. Those who did not meet these criteria were considered controls. Vaccine effectiveness (VE) to prevent severe cases and its 95% confidence interval were calculated. Results: A total of 403 patients were admitted with confirmed influenza. Of these, 98 (24.3%) developed severe influenza. Of the total, 50.6% were men and 47.1% were over 65 years of age. VE adjusted for influenza type, age and certain comorbidities was 40.6% (−21.9 to 71.1). In a segmented analysis, influenza vaccine was effective in preventing severe cases in all categories. It was particularly relevant in the 65+ age group (VEa=60.9%; −2.0 to 85.0) and in patients with influenza A (VEa=56.7%; 1.580.9). Conclusion: Influenza vaccination markedly reduced the occurrence of severe cases of influenza in hospitalised patients, therefore, it remains the main strategy to reduce morbidity and mortality and associated costs.(AU)

Frequency of Asthma Exacerbations and Upper Respiratory Tract Infections Among Adults With Asthma According to Vaccination Status: Does the annual influenza vaccine have a protective effect?

Objectives: Annual influenza vaccinations are recommended for asthma patients to prevent seasonal influenza and influenza-triggered asthma exacerbations. However, data on the beneficial effect of this vaccine on the frequency of asthma exacerbations are conflicting. Therefore, this study aimed to assess the effectiveness of the influenza vaccine in terms of reducing the frequency of asthma-related exacerbations and upper respiratory tract infections among adult patients with asthma. Methods: This retrospective cohort study was performed from January to December 2018 in Muscat Governorate, Oman. A total of 466 patients attending 9 randomly selected primary health centres in Muscat Governorate were enrolled in the study and followed up for one year post vaccination. Results: Most of the patients were female (70.6%) and had moderate persistent asthma (42.9%). There were 203 patients (43.6%) in the vaccinated group and 263 patients (56.4%) in the non-vaccinated group. A proportion of patients in each group had allergic rhinitis (28.6% and 25.5%, respectively). The frequency of upper respiratory tract infections over the one-year follow-up period was significantly lower in the vaccinated group than in the non-vaccinated group (37.9% versus 73%; relative risk [RR]: 2.299; 95% confidence interval [CI]: 1.834-2.882; P <0.001); however, there was no significant difference in terms of the frequency of asthma exacerbations (41.9% versus 45.2%; RR: 0.925; 95% CI: 0.750-1.141; P >0.050). Conclusion: The influenza vaccine significantly reduces the frequency of upper respiratory tract infections over the following year. However, it does not significantly reduce the frequency of asthma exacerbations among Omani adults with asthma. Further studies are recommended to support the protective effect of the vaccine in this regard.

Estradiol mediates greater germinal center responses to influenza vaccination in female than male mice.

Adult females of reproductive age develop greater antibody responses to inactivated influenza vaccines (IIV) than males. How sex, age, and sex steroid concentrations impact B cells and durability of IIV-induced immunity and protection over 4 months post-vaccination (mpv) was analyzed. Vaccinated adult females had greater germinal center B cell and plasmablast frequencies in lymphoid tissues, higher neutralizing antibody responses 1-4 mpv, and better protection against live H1N1 challenge than adult males. Aged mice, regardless of sex, had reduced B cell frequencies, less durable antibody responses, and inferior protection after challenge than adult mice, which correlated with diminished estradiol among aged females. To confirm that greater IIV-induced immunity was caused by sex hormones, four core genotype (FCG) mice were used, in which the testes-determining gene, Sry, was deleted from chromosome Y (ChrY) and transferred to Chr3 to separate gonadal sex (i.e., ovaries or testes) from sex chromosome complement (i.e., XX or XY complement). Vaccinated, gonadal female FCG mice (XXF and XYF) had greater numbers of B cells, higher antiviral antibody titers, and reduced pulmonary virus titers following live H1N1 challenge than gonadal FCG males (XYM and XXM). To establish that lower estradiol concentrations cause diminished immunity, adult and aged females received either a placebo or estradiol replacement therapy prior to IIV. Estradiol replacement significantly increased IIV-induced antibody responses and reduced morbidity after the H1N1 challenge among aged females. These data highlight that estradiol is a targetable mechanism mediating greater humoral immunity following vaccination among adult females.IMPORTANCEFemales of reproductive ages develop greater antibody responses to influenza vaccines than males. We hypothesized that female-biased immunity and protection against influenza were mediated by estradiol signaling in B cells. Using diverse mouse models ranging from advanced-age mice to transgenic mice that separate sex steroids from sex chromosome complement, those mice with greater concentrations of estradiol consistently had greater numbers of antibody-producing B cells in lymphoid tissue, higher antiviral antibody titers, and greater protection against live influenza virus challenge. Treatment of aged female mice with estradiol enhanced vaccine-induced immunity and protection against disease, suggesting that estradiol signaling in B cells is critical for improved vaccine outcomes in females.

Effectiveness of influenza vaccine in preventing severe cases of influenza: Season 2022/2023.

INTRODUCTION: Influenza poses a significant burden in terms of morbidity and mortality, with vaccination being one of the most effective measures for its prevention. Therefore, the aim of this study is to determine the effectiveness of the influenza vaccine in preventing cases of severe influenza in patients admitted to a tertiary hospital during the 2022/23 season. METHODS: Case-control study. All hospitalised patients with a positive result in an RT-PCR for influenza were included. Those who met the criteria for a severe case (pneumonia, sepsis, multi-organ failure, admission to ICU or exitus) were considered cases. Those who did not meet these criteria were considered controls. Vaccine effectiveness (VE) to prevent severe cases and its 95% confidence interval were calculated. RESULTS: A total of 403 patients were admitted with confirmed influenza. Of these, 98 (24.3%) developed severe influenza. Of the total, 50.6% were men and 47.1% were over 65 years of age. VE adjusted for influenza type, age and certain comorbidities was 40.6% (-21.9 to 71.1). In a segmented analysis, influenza vaccine was effective in preventing severe cases in all categories. It was particularly relevant in the 65+ age group (VEa = 60.9%; -2.0 to 85.0) and in patients with influenza A (VEa = 56.7%; 1.5-80.9). CONCLUSION: Influenza vaccination markedly reduced the occurrence of severe cases of influenza in hospitalised patients, therefore, it remains the main strategy to reduce morbidity and mortality and associated costs.

Influenza vaccination in pregnant women in Iceland 2010-2020 and the burden of influenza in pregnant women and their infants.

INTRODUCTION: Influenza vaccinations are recommended in pregnancy to protect both the pregnant woman and the unborn baby. The aim of this study was to assess the influenza vaccine uptake among pregnant women in Iceland in ten influenza seasons and to estimate the influenza disease burden on pregnant women and their infants. METHODS: This was a retrospective, descriptive study on influenza vaccine uptake among pregnant women and the burden of influenza and influenza-like illness (ILI) among pregnant women and their infants in ten influenza seasons. All women attending a 20-week ultrasound at Landspitali University Hospital in Reykjavik in August-April each influenza season 2010-2020 were included in the study. Data on influenza vaccinations and influenza/ILI diagnoses was collected from central national databases. RESULTS: The influenza vaccine uptake increased from 6.2 % in 2011-2012 to 37.5 % in 2019-2020. The incidence rate of influenza/ILI among pregnant women ranged from 5.5 to 22.1/1000 person-years. The estimated vaccine effectiveness in the ten influenza seasons was 34-100 %. The incidence rate of influenza/ILI among infants < 12 months of age was 0-13.4/1000 person-years. Influenza vaccinations in pregnancy are protective against influenza/ILI in pregnant women (IRR 0.36, 95 % CI 0.22-0.58), infants in the season of vaccination (IRR 0.40, 95 % CI 0.17-0.97) and probably for infants < 6 months of age (IRR 0.51, 95 % CI 0.22-1.21). CONCLUSIONS: Influenza vaccine coverage in pregnancy is suboptimal. Influenza vaccinations in pregnancy provide significant protection against influenza/ILI for pregnant women and infants in the season of vaccination. Initiatives to improve maternal vaccination coverage are needed.

Immunogenicity and safety of a quadrivalent recombinant influenza vaccine manufactured in Iran (FluGuard) in volunteers aged 18-60 years: A double-blind, non-inferiority, randomized controlled trial.

BACKGROUND: This study aimed to evaluate the non-inferiority of the FluGuard (a quadrivalent recombinant vaccine manufactured by Nivad Pharmed Salamat Company in Iran) by comparing its immunogenicity and safety with Vaxigrip Tetra (a quadrivalent inactivated vaccine manufactured by Sanofi Pasteur in France). MATERIALS AND METHODS: In this double-blind, randomized controlled trial, eligible volunteers aged 18-60 were randomized to receive either FluGuard or Vaxigrip Tetra vaccines. Immunogenicity was evaluated using the Hemagglutination Inhibition (HAI) assay and reported with the geometric mean titer (GMT), seroprotection, and seroconversion. In addition, vaccine safety was assessed by interviewing participants through phone calls. RESULTS: Out of 110 randomized volunteers, 51 and 53 were entered into the final analysis in the Vaxigrip and FluGuard groups, respectively. Vaxigrip had a higher seroprotection rate for the H1N1 strain compared with FluGuard (98 % vs. 91 %). Besides, FluGuard had higher seroprotection rates for H3N2 (74 % vs. 69 %), B-Yamagata (87 % vs. 84 %), and B-Victoria (66 % vs. 41 %) strains compared with Vaxigrip. In all four strains, FluGuard was non-inferior to Vaxigrip with the upper bounds of the 95 % CI on the ratio of the GMTs < 1.5: H1N1 (1.25), H3N2 (0.94), B-Yamagata (0.62), and B-Victoria (0.59). Furthermore, FluGuard was non-inferior to Vaxigrip with the upper bounds of the 95 % CI on the difference between the seroconversion rates < 10 %: H1N1 (2 %), H3N2 (10 %), B-Yamagata (-10 %), and B-Victoria (-29 %). The prevalence of solicited adverse drug reactions did not differ between groups. Furthermore, participants did not experience serious adverse events. CONCLUSION: Our findings support the non-inferiority of the FluGuard vaccine to the Vaxigrip vaccine regarding immunogenicity and safety. CLINICAL TRIAL REGISTRY: The study protocol was approved by the Iranian Registry of Clinical Trials (IRCT20210901052358N5).

Eficacia y seguridad de la vacunación antigripal pediátrica: una revisión sistemática / Efficacy and safety of pediatric flu vaccination: a systematic review

Introducción. Los a corren un mayor riesgo de infección por influenza en comparación con la población general. La Organización Mundial la Salud y las recomendaciones del Comité Asesor de Vacunas de la Asociación Española de Pediatría contemplan la vacunación anual como la forma más eficaz de prevenir la enfermedad. Por lo tanto, el propósito de esta revisión fue actualizar la información sobre eficacia y seguridad en la vacuna antigripal en niños y adolescentes. Material y métodos. Una búsqueda en cuatro bases de datos electrónicas (Scopus, Cumulative Index to Nursing and Allied Health Literature, MedLine / PubMed, Google Scholar y Cochrane), así como una búsqueda manual para identificar investigaciones originales publicadas entre 2012 y 2022. Se adoptaron las directrices de análisis (PRISMAcR) como elemento de informe preferido para revisiones sistemáticas. Resultados. Se incluyeron siete artículos de investigación originales donde se identificaron dos temas de la vacunación antigripal en niños/adolescentes sanos y con patologías. La eficacia (entre un 30% y un 80% aproximadamente) varió en función de la vacuna utilizada y los subtipos circulantes. La mayoría de las reacciones adversas fueron de intensidad leve y el evento adverso local más común informado fue dolor en el sitio de la inyección. Conclusiones. Destacamos positivamente la seguridad de la vacunación antigripal pediátrica en los estudios analizados, por el contrario, con respecto a la eficacia de la vacunación antigripal, observamos una amplia variabilidad de resultados. Existe una clara necesidad de seguir realizando estudios de eficacia y seguridad en el niño. (AU)

Introduction. Children are at a higher risk of influenza infection compared to the general population. The World Organization Health and recommendations of the Vaccine Advisory Committee of the Spanish Association of Pediatrics contemplate annual vaccination as the most effective way to prevent the disease. Therefore, the purpose of this review was to update information on efficacy and safety in the anti -shed vaccine in children and adolescents. Material and methods. A search in four electronic databases (Scopus, Cumulative Index to Nursing and Allied Health Literature, Medline / Pubmed, Google Scholar and Cochrane), as well as a manual search to identify original research published between 2012 and 2022. The guidelines of ANALYSIS (PRISMACR) as a preferred report element for systematic reviews. Results. Seven original research articles were included where two issues of antigripal vaccination were identified in healthy children/adolescents and with pathologies. The efficacy (between approximately 30% and 80%) varied depending on the vaccine used and circulating subtypes. Most adverse reactions were mild intensity, and the most common local adverse event was pain in the injection site. Conclusions. We positively highlight the safety of pediatric flu vaccination in analyzed studies, on the contrary, with respect to the efficacy of flu vaccination, we observe a wide variability of results. There is a clear need to continue conducting efficacy and safety studies in the child. (AU)

Transcriptomic Analysis Reveals Sixteen Potential Genes Associated with the Successful Differentiation of Antibody-Secreting Cells through the Utilization of Unfolded Protein Response Mechanisms in Robust Responders to the Influenza Vaccine.

The seasonal influenza vaccine remains one of the vital recommended infection control measures for the elderly with chronic illnesses. We investigated the immunogenicity of a single dose of influenza vaccine in 123 seronegative participants and classified them into four distinct groups, determined by the promptness of vaccine response, the longevity of humoral immunity, and the likelihood of exhibiting cross-reactivity. Subsequently, we used transcriptional profiling and differential gene expression analysis to identify potential genes directly associated with the robust response to the vaccine. The group of exemplary vaccine responders differentially expressed 16 genes, namely: MZB1, MYDGF, TXNDC5, TXNDC11, HSP90B1, FKBP11, PDIA5, PRDX4, CD38, SDC1, TNFRSF17, TNFRSF13B, PAX5, POU2AF1, IRF4, and XBP1. Our findings point out a list of expressed proteins that are related to B cell proliferation, unfolded protein response, and cellular haemostasis, as well as a linkage of these expressions to the survival of long-lived plasma cells.

Downregulation of hypocretin/orexin after H1N1 Pandemrix vaccination of adolescent mice.

Narcolepsy type 1 (NT1), characterized by the loss of hypocretin/orexin (HCRT) production in the lateral hypothalamus, has been linked to Pandemrix vaccination during the 2009 H1N1 pandemic, especially in children and adolescents. It is still unknown why this vaccination increased the risk of developing NT1. This study investigated the effects of Pandemrix vaccination during adolescence on Hcrt mRNA expression in mice. Mice received a primary vaccination (50 µL i.m.) during prepubescence and a booster vaccination during peri-adolescence. Hcrt expression was measured at three-time points after the vaccinations. Control groups included both a saline group and an undisturbed group of mice. Hcrt expression was decreased after both Pandemrix and saline injections, but 21 days after the second injection, the saline group no longer showed decreased Hcrt expression, while the Pandemrix group still exhibited a significant reduction of about 60% compared to the undisturbed control group. This finding suggests that Pandemrix vaccination during adolescence influences Hcrt expression in mice into early adulthood. The Hcrt mRNA level did not reach the low levels known to induce NT1 symptoms, instead, our finding supports the multiple-hit hypothesis of NT1 that states that several insults to the HCRT system may be needed to induce NT1 and that Pandemrix could be one such insult.

Factors Associated With Influenza Vaccination During Pregnancy: A Real-World Evidence-Based Study.

Pregnant women are at increased risk of influenza-related complications. However, the rate of influenza vaccination among pregnant women in Taiwan is low. By analyzing real-world data in this study, we investigated the factors associated with influenza vaccination during pregnancy in Taiwan. This study was a cross-sectional study. We collected real-world data from 2 databases in Taiwan: the Birth Certificate Database and the National Health Insurance Research Database. The study population was pregnant between October 2014 and December 2016 in Taiwan. The multivariate logistic regression was performed to identify factors associated with influenza vaccination, including maternal sociodemographics, trimester, comorbidities, and health-care utilization. The vaccination rate of among pregnant women was 8.2%. Factors significantly associated with a high likelihood of influenza vaccination were age between 30 and 34 years (odds ratio [OR]: 1.14; 95% confidence interval [CI]: 1.10-1.19), second trimester (OR: 1.80; 95% CI: 1.75-1.85), income equal to or exceeding NT$ 38 201 (OR: 1.92; 95% CI: 1.86-1.99), hypertension (OR: 1.16; 95% CI: 1.05-1.29), cardiovascular disease (OR: 1.29; 95% CI: 1.17-1.42), autoimmune disease (OR: 1.47; 95% CI: 1.38-1.58), and chronic pulmonary disease (OR: 1.24; 95% CI: 1.18-1.31). A low level of urbanization, at least 1 hospitalization in the previous year, and the presence of pregnancy complications (eg, gestational diabetes, preeclampsia, and placenta previa) were associated with a lower likelihood rate of influenza vaccination. The influenza vaccination rate among pregnant women in Taiwan was low. Age, gestational age, income level, urbanization level, hypertension, cardiovascular disease, autoimmune disease, chronic pulmonary disease, and pregnancy complications may be associated with influenza vaccination among pregnant women.

Mucosal correlates of protection after influenza viral challenge of vaccinated and unvaccinated healthy volunteers.

The induction of systemic antibody titers against hemagglutinin has long been the main focus of influenza vaccination strategies, but mucosal immunity has also been shown to play a key role in the protection against respiratory viruses. By vaccinating and challenging healthy volunteers, we demonstrated that inactivated influenza vaccine (IIV) modestly reduced the rate of influenza while predominantly boosting serum antibody titers against hemagglutinin (HA) and HA stalk, a consequence of the low neuraminidase (NA) content of IIV and the intramuscular route of administration. The viral challenge induced nasal and serum responses against both HA and NA. Correlations between mucosal IgA and serum IgG against specific antigens were low, whether before or after challenge, suggesting a compartmentalization of immune responses. Even so, volunteers who developed viral shedding for multiple days had lower baseline titers across both systemic and mucosal compartments as compared to those with no shedding or a single day of shedding. Regression analysis showed that pre-challenge HA inhibition titers were the most consistent correlate of protection across clinical outcomes combining shedding and symptoms, with NA inhibition titers and HA IgG levels only predicting the duration of shedding. Despite the inclusion of data from multiple binding and functional antibody assays against HA and NA performed on both serum and nasal samples, multivariate models were unable to account for the variability in outcomes, emphasizing our imperfect understanding of immune correlates in influenza and the importance of refining models with assessments of innate and cellular immune responses.IMPORTANCEThe devastating potential of influenza has been well known for over 100 years. Despite the development of vaccines since the middle of the 20th century, influenza continues to be responsible for substantial global morbidity and mortality. To develop next-generation vaccines with enhanced effectiveness, we must synthesize our understanding of the complex immune mechanisms culminating in protection. Our study outlines the differences in immune responses to influenza vaccine and influenza infection, identifying potential gaps in vaccine-induced immunity, particularly at the level of the nasal mucosa. Furthermore, this research underscores the need to refine our imperfect models while recognizing potential pitfalls in past and future attempts to identify and measure correlates of protection.

Early influenza vaccine effectiveness estimates using routinely collected data, Alberta, Canada, 2023/24 season.

Timely and precise influenza vaccine effectiveness (VE) estimates are needed to guide public health messaging and impact vaccine uptake immediately. Using routinely collected laboratory, vaccination and health administrative data from Alberta, Canada, we estimated influenza VE against infection for the 2023/24 season on a near real-time basis, to late December, at 61% (95% CI: 58-64) against influenza A(H1N1), 49% (95% CI: 28-63) against influenza A(H3N2) and 75% (95% CI: 58-85) against influenza B.

Safety and immunogenicity of locally produced trivalent inactivated influenza vaccine (Tri Fluvac) in healthy Thai adults aged 18-64 years in Nakhon Phanom: A Phase III double blinded, three-arm, randomized, controlled trial.

BACKGROUND: Domestic influenza vaccine production facilitates a sustainable supply for mitigating seasonal influenza and improves national health security by providing infrastructure and experience for pandemic vaccine production, if needed. METHODS: A Phase III, double blind, randomized controlled trial was conducted from Sep 2019-Oct 2020 in healthy adults 18-64 years in Nakhon Phanom, Thailand. Randomization (3:3:1) compared study vaccine (Tri Fluvac), saline placebo, and an active comparator (licensed vaccine). Primary outcomes were superior efficacy compared to placebo based on RT-PCR-confirmed influenza virus infection within 12 months and non-inferiority compared to active comparator based on immunogenicity (HAI assay) at 28 days. Safety was also assessed. RESULTS: The trial enrolled 4,284 participants (Tri Fluvac = 1,836; placebo = 1,836; active comparator = 612). There were 29 RT-PCR positive influenza infections (10 Tri Fluvac, 5.5/1,000 PY; 19 placebo, 10.4/1,000PY; 0 comparator) for an absolute protective efficacy of 46.4 (95 % CI = -22.0-76.5) compared with placebo, but the power was 43.7 %. Seroconversion difference rates between Tri Fluvac and comparator at Day 28 were 1.74 (95 % CI: -2.77, 6.25), 2.22 (-2.40, 6.84), and -0.57 (-5.41, 4.27) for A(H1N1), A(H3N2), and B strains, respectively. Adverse and severe adverse events occurred in 175 (9.5 %) Tri Fluvac, 177 (10.8 %) placebo, and 66 (10.8 %) comparator arms (p-value = 0.437, Tri Fluvac vs. comparator) CONCLUSIONS: Tri Fluvac was well tolerated, and immunogenicity was non-inferior to the active comparator, meeting U.S. Food and Drug Administration (FDA) criteria for adult vaccine licensure. Few acute respiratory infections were reported during intense COVID-19 pandemic restrictions, resulting in insufficient power to evaluate clinical efficacy.

[Efficacy and safety of pediatric flu vaccination: a systematic review]. / Eficacia y seguridad de la vacunación antigripal pediátrica: una revisión sistemática.

OBJECTIVE: Children are at a higher risk of influenza infection compared to the general population. The World Organization Health and recommendations of the Vaccine Advisory Committee of the Spanish Association of Pediatrics contemplate annual vaccination as the most effective way to prevent the disease. Therefore, the purpose of this review was to update information on efficacy and safety in the anti -shed vaccine in children and adolescents. METHODS: A search in four electronic databases (Scopus, Cumulative Index to Nursing and Allied Health Literature, Medline / Pubmed, Google Scholar and Cochrane), as well as a manual search to identify original research published between 2012 and 2022. The guidelines of ANALYSIS (PRISMACR) as a preferred report element for systematic reviews. RESULTS: Seven original research articles were included where two issues of antigripal vaccination were identified in healthy children/adolescents and with pathologies. The efficacy (between approximately 30% and 80%) varied depending on the vaccine used and circulating subtypes. Most adverse reactions were mild intensity, and the most common local adverse event was pain in the injection site. CONCLUSIONS: We positively highlight the safety of pediatric flu vaccination in analyzed studies, on the contrary, with respect to the efficacy of flu vaccination, we observe a wide variability of results. There is a clear need to continue conducting efficacy and safety studies in the child.

Sense of community belonging and influenza vaccine uptake in Canada.

OBJECTIVES: The objectives of this study are to determine the prevalence of influenza vaccine uptake across Canadians aged 18 to 64 years with different sense of community belonging (SoCB) and whether SoCB is associated with uptake of the seasonal influenza vaccine. METHODS: We combined the 2007 to 2014 cycles of the nationally representative Canadian Community Health Survey (N = 301,802). The main exposure, SoCB, was measured as "strong" vs "weak." The outcome of interest was receipt of the influenza vaccine within the preceding 12 months. We used robust Poisson regression to estimate prevalence ratios. Normalized weights were utilized to account for the unequal probability of sample selection. RESULTS: The adjusted prevalence of uptake of seasonal influenza vaccines was modestly greater for individuals with a strong SoCB compared to those with a weak SoCB (PR, 1.12; 95% CI, 1.11, 1.13). Older individuals, females, those with post-secondary education, non-immigrants, those who are married, those with at least one chronic condition, and those residing in a jurisdiction where pharmacists are authorized to administer influenza vaccine and/or where influenza vaccine is universally funded for all residents were more likely to have received an influenza vaccine within the past year. CONCLUSION: Canadians with a strong SoCB had modestly higher uptake of seasonal influenza vaccines. While the association is modest, findings suggest that SoCB may be an important component to investigate further and to consider in efforts aimed to increase the uptake of seasonal influenza vaccines.

RéSUMé: OBJECTIFS: Cette étude vise à déterminer la prévalence de la vaccination antigrippale chez les Canadiens âgés de 18 à 64 ans ayant un sentiment d'appartenance à la communauté différent et de déterminer si ce sentiment est associé à la vaccination contre la grippe saisonnière. MéTHODES: Nous avons combiné les cycles 2007 à 2014 de l'Enquête sur la santé dans les collectivités canadiennes représentative sur le plan national (N = 301 802). L'exposition principale, à savoir le sentiment d'appartenance à la communauté, a été mesurée comme « forte ¼ ou « faible ¼. Le résultat recherché était la réception du vaccin antigrippal au cours des douze derniers mois. Nous avons utilisé une régression de Poisson robuste pour estimer les rapports de prévalence (RP). Des poids normalisés ont été utilisés pour tenir compte de la probabilité inégale de l'échantillonnage. RéSULTATS: La prévalence ajustée de la vaccination contre la grippe saisonnière était légèrement plus élevée chez les personnes ayant un sentiment fort d'appartenance à la communauté par rapport à celles dont ce sentiment était faible (RP : 1,12; IC de 95 % : 1,11, 1,13). Les personnes plus âgées, les femmes, les personnes ayant fait des études supérieures, les non-immigrants, les personnes mariées, les personnes souffrant d'au moins une maladie chronique et les personnes résidant dans une juridiction où les pharmaciens sont autorisés à administrer le vaccin antigrippal et/ou où le vaccin antigrippal est financé de manière universelle pour tous les résidents, étaient plus susceptibles d'avoir reçu un vaccin antigrippal au cours de l'année écoulée. CONCLUSION: Les Canadiens ayant un sentiment fort d'appartenance à la communauté étaient légèrement plus nombreux à s'être fait vacciner contre la grippe saisonnière. Bien que l'association soit modeste, les résultats suggèrent que le sentiment d'appartenance à la communauté pourrait être un élément important à étudier davantage et à prendre en compte dans les efforts visant à augmenter la vaccination contre la grippe saisonnière.