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Explore pediatric staff experiences administering the second influenza vaccine dose. Qualitative focus groups/interviews. As part of the National Institutes of Health-funded Flu2Text randomized control trial of text message reminders for second influenza vaccine dose, we conducted seven focus groups and four individual interviews (n = 39 participants total) with clinicians and staff from participating practices from the American Academy of Pediatrics' Pediatric Research in Office Settings (PROS) Network. Of 37 participating practices, 10 were selected through stratified sampling of practices with highest (n = 5) and lowest (n = 5) randomized controlled trial effect sizes. A semi-structured discussion guide included questions that addressed parental, practice, and health system barriers/facilitators to second influenza vaccine dose administration. Using the Systems Model of Clinical Preventive Care as a conceptual framework, two investigators independently coded transcripts (Κ = 0.86, high agreement) with NVivo 12 Plus. Coding inconsistencies were resolved by consensus. Clinicians/staff reported that administering the second influenza vaccine dose in a season was more complex than other childhood vaccines. They highlighted parental uncertainty about the need for the second dose and the difficulty and inconvenience of bringing children back to the office as important barriers. Caregiver–staff relationships were perceived as helpful in getting children vaccinated with their second dose and vaccine reminders were seen as important cues-to-action. Ensuring receipt of two doses of the influenza vaccine in a given season presents unique challenges. Themes identified provide a framework for understanding opportunities to bolster second dose receipt, including explaining why two doses are needed, offering flexible hours for vaccination, and sending vaccine reminders. [ABSTRACT FROM AUTHOR]

This manuscript offers an in-depth comparative examination of the effectiveness of higher-dose (double standard-dose and high-dose) influenza vaccines in contrast to a single standard-dose vaccine when it comes to alleviating major cardiovascular events. Meta-Analysis. To conduct this study, an exhaustive search was carried out in the medical English literature using databases such as PubMed/MEDLINE, EMBASE, and the Cochrane CENTRAL until 10 April 2024. The evaluation of associations was achieved through the calculation of pooled relative risks (RRs) accompanied by their corresponding 95% confidence intervals (CIs). A meticulous analysis encompassed a comprehensive cohort of 68,713 patients. Among these participants, 34,430 individuals were randomly assigned to receive a higher-dose influenza vaccination, whereas 34,283 received the standard influenza vaccination. Contrary to initial expectations, a higher-dose influenza vaccine did not manifest elevated efficacy compared to the standard-dose vaccine in terms of mitigating major cardiovascular events. The computed pooled RR stood at 1.0, accompanied by a 95% CI ranging from 0.93 to 1.10. While this systematic review and meta-analysis did not find a statistically significant advantage of higher-dose influenza vaccines over a single standard-dose vaccine in preventing major cardiovascular events, the observed trend towards risk reduction warrants continued investigation. These findings contribute to the ongoing dialogue surrounding vaccination strategies and their implications for cardiovascular outcomes. [ABSTRACT FROM AUTHOR]

To investigate the short-term and long-term effectiveness of different levels of financial incentives on increasing the willingness to vaccinate and vaccine uptake. A randomized controlled trial was conducted to investigate the effectiveness of financial incentives of three groups with monetary incentives (CNY 20, CNY 40, and CNY 60; 1 CNY = 0.13 EUR) vs. a control group—CNY 0—on influenza vaccine uptake among 720 older adults (≥60 years) in Beijing, China. The primary outcome was vaccine uptake, and the secondary outcomes were intention to vaccinate and length of time to immunization. Financial incentive significantly promoted higher intention to influenza vaccination (120/178 [67.42%] vs. 442/542 [81.55%]; Relative Risk [RR], 1.21; 95% CI, 1.02–1.42) and higher vaccination participation (74/178 [41.57%] vs. 316/542 [58.30%]; RR, 1.39; 95% CI, 1.10–1.75). CNY 60 had the largest impact on the intention to vaccinate (15.00% vs. 13.48% and 13.90%) and vaccination uptake (19.42% vs. 14.05% and 16.67%) compared with CNY 20 and CNY 40. Time to vaccination was significantly lower among participants receiving incentives than those without ([37.21 days; 95% CI, 34.33–39.99] vs. [48.27 days; 95% CI, 43.47–53.07]; Hazard Ratio [HR] 1.57, 95% CI 1.22–2.03). We found no long-term influence of financial incentives on vaccination decisions in the following year (217/542, 40.04% vs. 65/178, 36.52%; RR 1.08, 95% CI 0.82–1.42). Our study suggests that modest financial incentives will boost short-term influenza vaccination rates and shorten the length of time to immunization in China. No one single-time financial incentive had a long-term effect on future vaccination behaviours or helped establish regular vaccination behaviours. [ABSTRACT FROM AUTHOR]

Within influenza vaccine effectiveness (VE) studies at primary care level with a laboratory-confirmed outcome, clinical case definitions for recruitment of patients can vary. We used the 2022–23 VEBIS primary care European multicentre study end-of-season data to evaluate whether the clinical case definition affected IVE estimates. We estimated VE using a multicentre test-negative case-control design. We measured VE against any influenza and influenza (sub)types, by age group (0–14, 15–64, ≥65 years) and by influenza vaccine target group, using logistic regression. We estimated IVE among patients meeting the European Union (EU) acute respiratory infection (ARI) case definition and among those meeting the EU influenza-like illness (ILI) case definition, including only sites providing information on specific symptoms and recruiting patients using an ARI case definition (as the EU ILI case definition is a subset of the EU ARI one). We included 24 319 patients meeting the EU ARI case definition, of whom 21 804 patients (90 %) meet the EU ILI case definition, for the overall pooled VE analysis against any influenza. The overall and influenza (sub)type-specific VE varied by ≤2 % between EU ILI and EU ARI populations. Among all analyses, we found similar VE estimates between the EU ILI and EU ARI populations, with few (10%) additional non-ILI ARI patients recruited. These results indicate that VE in the 2022–23 influenza season was not affected by use of a different clinical case definition for recruitment, although we recommend investigating whether this holds true for next seasons. [ABSTRACT FROM AUTHOR]

Psychological distress has been associated with dampened antibody production following vaccination. Questions remain, however, about whether psychological distress influences vaccine response uniformly across the lifespan, and whether changes in distress result in changes in antibody production across the same period. Participants (N = 148; M age = 32.2 years, SD = 19.7, range = 12–80 years) took part in consecutive vaccine studies during the 2017–2018 and 2018–2019 influenza seasons. Each influenza season, they reported on their depressive symptoms, provided blood samples, and received the standard influenza vaccine. Participants then provided a second blood sample one month later. Antibody titers were examined pre- and post-vaccination. Analyses examined both within-season and across-season effects of depressive symptoms, age, and their interaction on vaccine response. Within-season analyses revealed that age predicted antibody response during both seasons (2017–2018 and 2018–2019). Neither depressive symptoms nor the interaction with age were associated with antibody response to vaccination within either season. Across the two seasons, age significantly moderated the association between change in depressive symptoms and change in antibody production. For people who were 48 or older, increases in depressive symptoms across the two seasons were associated with a less robust response to the vaccine in the second season relative to the first season. For people younger than 48, changes in depressive symptoms were not significantly related to changes in antibody production. These findings highlight the important role of mental health for older adults' vaccine response, which could have clinical relevance for protection against disease. [ABSTRACT FROM AUTHOR]

Annual influenza vaccination is crucially recommended for the elderly to maintain humoral immunity. Insufficient coverage requires us to understand the determinants of their influenza behaviors and how these patterns impact vaccination choices. Data from 540 Beijing residents aged over 65 were collected through interviews, capturing vaccination history and sociodemographic details. Individual influenza vaccination records from 2016 to 2020 were obtained from China's Immunization Information Systems. A latent class model identified three vaccination patterns. Multinomial logistic regression assessed relative risk ratios (RRRs) for vaccination based on sociodemographic factors. Vaccination patterns were used to predict future vaccination likelihood. The analysis revealed three groups: sporadically vaccinated (63.33%), occasionally vaccinated (18.71%), and frequently vaccinated (17.96%). Factors associated with frequent vaccination included age over 70 (RRR = 2.81), lower income (RRR = 0.39), higher vaccine hesitancy (RRR = 3.10), multiple chronic conditions (RRR = 2.72), and rural residence (RRR = 2.48). The frequently vaccinated group was more likely to sustain regular vaccination habits in subsequent years compared to the occasionally vaccinated group. Only 17.96% of Beijing's older population exhibited a consistent influenza vaccination pattern. Older age, rural residency, and chronic diseases correlated with repeated influenza vaccination. Segmenting the population based on past vaccination behavior can aid in designing targeted interventions to improve vaccination rates. [ABSTRACT FROM AUTHOR]

• Influenza NP, HA, and M2e show potential for a universal vaccine, with anticipated synergistic effects. • Nasal mucosal delivery overcomes pre-existing immunity against adenovirus-based vaccines. • Combined administration of NP and HA-M2e viral vectors exhibits dose-sparing effect and safety in preclinical studies. It is necessary to develop universal vaccines that act broadly and continuously to combat regular seasonal epidemics of influenza and rare pandemics. The aim of this study was to find the optimal dose regimen for the efficacy and safety of a mixture of previously developed recombinant adenovirus-based vaccines that expressed influenza nucleoprotein, hemagglutinin, and ectodomain of matrix protein 2 (rAd/NP and rAd/HA-M2e). The vaccine efficacy and safety were measured in the immunized mice with the mixture of rAd/NP and rAd/HA-M2e intranasally or intramuscularly. The minimum dose that would be efficacious in a single intranasal administration of the vaccine mixture and cross-protective efficacy against various influenza strains were examined. In addition, the immune responses that may affect the cross-protective efficacy were measured. We found that intranasal administration is an optimal route for 107 pfu of vaccine mixture, which is effective against pre-existing immunity against adenovirus. In a study to find the minimum dose with vaccine efficacy, the 106 pfu of vaccine mixture showed higher antibody titers to the nucleoprotein than did the same dose of rAd/NP alone in the serum of immunized mice. The 106 pfu of vaccine mixture overcame the morbidity and mortality of mice against the lethal dose of pH1N1, H3N2, and H5N1 influenza infections. No noticeable side effects were observed in single and repeated toxicity studies. We found that the mucosal administration of adenovirus-based universal influenza vaccine has both efficacy and safety, and can provide cross-protection against various influenza infections even at doses lower than those previously known to be effective. [ABSTRACT FROM AUTHOR]

• Study assessed four adverse events following 2022–2023 seasonal influenza vaccines. • Study population was 12.7 million Medicare enrollees 65 years and older. • There was no increase in post-vaccination incidence rates for three adverse events. • Anaphylaxis rates were elevated and possibly modified by concomitant vaccination. While safety of influenza vaccines is well-established, some studies have suggested potential associations between influenza vaccines and certain adverse events (AEs). This study examined the safety of the 2022–2023 influenza vaccines among U.S. adults ≥ 65 years. A self-controlled case series compared incidence rates of anaphylaxis, encephalitis/encephalomyelitis, Guillain-Barré Syndrome (GBS), and transverse myelitis following 2022–2023 seasonal influenza vaccinations (i.e., any, high-dose or adjuvanted) in risk and control intervals among Medicare beneficiaries ≥ 65 years. We used conditional Poisson regression to estimate incidence rate ratios (IRRs) and 95 % confidence intervals (CIs) adjusted for event-dependent observation time and seasonality. Analyses also accounted for uncertainty from outcome misclassification where feasible. For AEs with any statistically significant associations, we stratified results by concomitant vaccination status. Among 12.7 million vaccine recipients, we observed 76 anaphylaxis, 276 encephalitis/encephalomyelitis, 134 GBS and 75 transverse myelitis cases. Only rates of anaphylaxis were elevated in risk compared to control intervals. With all adjustments, an elevated, but non-statistically significant, anaphylaxis rate was observed following any (IRR: 2.40, 95% CI: 0.96–6.03), high-dose (IRR: 2.31, 95% CI: 0.67–7.91), and adjuvanted (IRR: 3.28, 95% CI: 0.71–15.08) influenza vaccination; anaphylaxis IRRs were 2.54 (95% CI: 0.49–13.05) and 1.64 (95% CI: 0.38–7.05) for persons with and without concomitant vaccination, respectively. Rates of encephalitis/encephalomyelitis, GBS, or transverse myelitis were not elevated following 2022–2023 seasonal influenza vaccinations among U.S. adults ≥ 65 years. There was an increased rate of anaphylaxis following influenza vaccination that may have been influenced by concomitant vaccination. [ABSTRACT FROM AUTHOR]

Virus like particles (VLPs) have been well recognized as one of the most important vaccine platforms due to their structural similarity to natural viruses to induce effective humoral and cellular immune responses. Nevertheless, lack of viral nucleic acids in VLPs usually leads the vaccine candidates less efficient in provoking innate immune against viral infection. Here, we constructed a biomimetic dual antigen hybrid influenza nanovaccines THM-HA@Mn with robust immunogenicity via in situ synthesizing a stimulator of interferon genes (STING) agonist Mn 3 O 4 inside the cavity of a recombinant Hepatitis B core antigen VLP (HBc VLP) having fused SpyTag and influenza M2e antigen peptides (Tag-HBc-M2e, THM for short), followed by conjugating a recombinant hemagglutinin (rHA) antigen on the surface of the nanoparticles through SpyTag/SpyCatcher ligating. Such inside Mn 3 O 4 immunostimulator-outside rHA antigen design, together with the chimeric M2e antigen on the HBc skeleton, enabled the synthesized hybrid nanovaccines THM-HA@Mn to well imitate the spatial distribution of M2e/HA antigens and immunostimulant in natural influenza virus. In vitro cellular experiments indicated that compared with the THM-HA antigen without Mn 3 O 4 and a mixture vaccine consisting of THM-HA + MnOx, the THM-HA@Mn hybrid nanovaccines showed the highest efficacies in dendritic cells uptake and in promoting BMDC maturation, as well as inducing expression of TNF-α and type I interferon IFN-β. The THM-HA@Mn also displayed the most sustained antigen release at the injection site, the highest efficacies in promoting the DC maturation in lymph nodes and germinal center B cells activation in the spleen of the immunized mice. The co-delivery of immunostimulant and antigens enabled the THM-HA@Mn nanovaccines to induce the highest systemic antigen-specific antibody responses and cellular immunogenicity in mice. Together with the excellent colloid dispersion stability, low cytotoxicity, as well as good biosafety, the synthetic hybrid nanovaccines presented in this study offers a promising strategy to design VLP-based vaccine with robust natural and adaptive immunogenicity against emerging viral pathogens. [Display omitted] • Mn nanoadjuvant was in situ bio-mineralized inside recombination HBc VLP. • THM-HA@Mn hybrid influenza nanovaccine was fabricated with HA and M2e as antigens. • The nanovaccines inmate the spatial distribution of antigens and adjuvant in natural influenza virus. • Hybrid nanovaccines promote the maturation of DC both in vitro and in vivo. • Hybrid nanovaccines induce robust antibodies and T cell immunity against influenza. [ABSTRACT FROM AUTHOR]

The influenza mortality burden has remained substantial in the United States (US) despite relatively high levels of influenza vaccine uptake. This has led to questions regarding the effectiveness of the program against this outcome, particularly in the elderly. The aim of this evaluation was to develop and explore a new approach to estimating the population-level effect of influenza vaccination uptake on pneumonia and influenza (P&I) associated deaths. Using publicly available data we examined the association between state-level influenza vaccination and all-age P&I associated deaths in the US from the 2013–2014 influenza season to the 2018–2019 season. In the main model, we evaluated influenza vaccine uptake in all those age 6 months and older. We used a mixed-effects regression analysis with generalised least squares estimation to account for within state correlation in P&I mortality. From 2013–2014 through 2018–2019, the total number of all-age P&I related deaths during the influenza seasons was 480,111. The mean overall cumulative influenza vaccine uptake (age 6 months and older) across the states and years considered was 46.7%, with higher uptake (64.8%) observed in those aged ≥ 65 years. We found that overall influenza vaccine uptake (6 months and older) had a statistically significant protective association with the P&I death rate. This translated to a 0.33 (95% CI: 0.20, 0.47) per 100,000 population reduction in P&I deaths in the influenza season per 1% increase in overall influenza vaccine uptake. These results using a population-level statistical approach provide additional support for the overall effectiveness of the US influenza vaccination program. This reassurance is critical given the importance of ensuring confidence in this life saving program. Future research is needed to expand on our approach using more refined data. [ABSTRACT FROM AUTHOR]

The objective of the study was to estimate the economic cost benefit of funding influenza vaccination to all Australian adults 50–64 years and predict its effect on sudden cardiac arrest (SCA) deaths and hospitalisation. We combined SCA hospitalisation data from the Australian Institute of Health and Welfare (AIHW) with survival, vaccination, and cost parameters from published literature to create a model estimating the cost benefit of universally funded influenza vaccinations to prevent SCA deaths and hospitalisation. Costs were considered from a government perspective and included cost of vaccines and GP consultations, whilst averted deaths were estimated through the age-adjusted value of a statistical life. The target policy was estimated to prevent 278 SCA hospitalisations and 1269 SCA deaths. This would result in cost-savings of almost $4 billion annually, with an incremental benefit-cost ratio (BCR) of 59.94. The majority of savings were associate with averted deaths. When a sensitivity analysis was performed by altering statistical life year values and reducing life years left, the cost-saving remained significant with a minimum BCR of 29.97 derived. Reducing SCA through extended vaccination including adults 50–64 years is likely to be a cost beneficial policy from a governmental perspective. SCA deaths account for a significant economic loss due to the high mortality rate, which was far greater than the costs saved through averted hospitalisations. More accurate parameters are needed to improve the reliability of these estimate; however, this model can be used as a basis for further research into the economic impact of SCA. [ABSTRACT FROM AUTHOR]

• H3N2 serology titres were highest in those with current season influenza vaccination. • Titres were higher in those with past season vaccination over those with no vaccination recorded. • Influenza vaccination protection was good against influenza requiring emergency care in children. • Vaccine effectiveness in adults was modest. We present England 2021/22 end-of-season adjusted vaccine effectiveness (aVE) against laboratory confirmed influenza related emergency care use in children aged 1–17 and in adults aged 50+, and serological findings in vaccinated vs unvaccinated adults by hemagglutination inhibition assay. Influenza vaccination has been routinely offered to all children aged 2–10 years and adults aged 65 years + in England. In 2021/22, the offer was extended to children to age 15 years, and adults aged 50–64 years. Influenza activity rose during the latter half of the 2021/22 season, while remaining comparatively low due to COVID-19 pandemic control measures. Influenza A(H3N2) strains predominated. A test negative design was used to estimate aVE by vaccine type. Cases and controls were identified within a sentinel laboratory surveillance system. Vaccine histories were obtained from the National Immunisation Management Service (NIMS), an influenza and COVID-19 vaccine registry. These were linked to emergency department presentations (excluding accidents) with respiratory swabbing ≤ 14 days before or ≤ 7 days after presentation. Amongst adults, 423 positive and 32,917 negative samples were eligible for inclusion, and 145 positive and 6,438 negative samples among children. Those admitted to hospital were further identified. In serology against the circulating A(H3N2) A/Bangladesh/4005/2020-like strain, 61 % of current season adult vaccinees had titres ≥ 1:40 compared to 17 % of those unvaccinated in 2020/21 or 2021/22 (p < 0.001). We found good protection from influenza vaccination against influenza requiring emergency care in children (72.7 % [95 % CI 52.7, 84.3 %]) and modest effectiveness in adults (26.1 % [95 % CI 4.5, 42.8 %]). Adult VE was higher for A(H1N1) (81 % [95 % CI 50, 93 %]) than A(H3N2) (33 % [95 % CI 6, 53 %]). Consistent protection was observable across preschool, primary and secondary school aged children. Imperfect test specificity combined with very low prevalence may have biased estimates towards null. With limited influenza circulation, the study could not determine differences by vaccine types. [ABSTRACT FROM AUTHOR]

Immune checkpoint inhibitor (ICI) therapy for patients undergoing cancer treatment carries a risk of severe immune-related adverse events (IRAEs). Questions remain about whether seasonal influenza vaccination might increase the risk of developing IRAEs among these patients given that vaccines are immunomodulatory. Previous vaccine safety studies on patients with cancer prescribed ICI therapy have demonstrated conflicting results. Using health administrative data from Ontario, Canada among adults diagnosed with cancer who had been prescribed ICI therapy and who had received an influenza vaccine from 2012 to 2019, we conducted a self-controlled case series study. The pre-vaccination control period started 42-days post-ICI initiation until 14-days prior to vaccination, the risk period was 1–42 days post-vaccination, and the post-vaccination control period was after the risk period until ICI discontinuation or a maximum period of two years. Emergency department (ED) visit(s) and/or hospitalization for any cause after ICI initiation was used to identify severe IRAEs. We fitted a fixed-effects Poisson regression model accounting for seasonality and calendar time to estimate relative incidence of IRAEs between risk and control periods. We identified 1133 records of cancer patients who received influenza vaccination while prescribed ICI therapy. Most were aged ≥ 66 years (73 %), were male (63 %), had lung cancer (54 %), and had received ICI therapy with a programmed cell death protein 1(PD-1) inhibitor (91 %). A quarter (26 %) experienced an ED visit and/or hospitalization during the observation period. Rates of ED visits and/or hospitalizations in the risk vs. control periods were similar, with an incidence rate ratio of 1.04 (95 % CI: 0.75–1.45). Subgroup and sensitivity analyses yielded similar results. Seasonal influenza vaccination was not associated with an increased incidence of ED visit or hospitalization among adults with cancer treated with ICI therapy and our results support further evidence of vaccine safety. [ABSTRACT FROM AUTHOR]

• The evidence of benefits with influenza vaccination for mortality is inconclusive. • RCTs reported to date suggest a reduction in the risk of all-cause hospitalization. • Based on two randomized trials, influenza vaccination appears safe. The effects of seasonal influenza vaccination on cardiovascular disease (CVD) outcomes, including among individuals with established CVD, are uncertain. To evaluate the efficacy and safety of influenza vaccines compared to no vaccines or placebo for preventing all-cause/CVD mortality or all-cause/CVD hospitalization in the general population and in populations with pre-existing CVD, we conducted a living systematic review (LSR) and prospective meta-analysis (PMA). Published randomized controlled trials (RCT) and observational studies between 1994 and 2023 were searched. PRISMA guidelines were followed in the extraction of study details, and risk of bias was assessed using the Cochrane tools. Analyses were stratified by study design and CVD history. Study quality was evaluated using GRADE system. Meta analyses based on random-effects models were performed between July and October 2022. Pooled risk ratios (RRs) for all-cause/CVD mortality and all-cause/CVD hospitalization were main outcomes. Six published RCTs comprising 12,662 participants (mean age, 62 years; 45 % women; 8,797 with pre-existing CVD) and 37 observational studies comprising 6,311,703 participants (mean age, 49 years; 50 % women; 1,189,955 with pre-existing CVD) were included. Only those RCTs judged to be low risk were included in the analyses, and observational studies at anything greater than moderate risk of bias were excluded. In RCTs, influenza vaccine was not significantly associated with lower all-cause mortality (RR, 0.85; 95 %CI, 0.61–1.17), cardiovascular death (RR, 0.80; 95 %CI, 0.60–1.07), or CVD hospitalization (RR, 0.69; 95 %CI, 0.47–1.02). A statistically significant reduction in all-cause hospitalization (RR, 0.86; 95 %CI, 0.76–0.97) was observed. The evidence level was assessed as moderate for all-cause hospitalization, and low for other outcomes. Overall, observational studies suggested a stronger protective association between influenza vaccination and outcomes, except for CVD hospitalization. Based on RCTs, there was no difference in the effects of influenza vaccination on all-cause mortality among the general population compared to those with pre-existing CVD, although the summary point estimate favored benefits only in those with pre-existing CVD. While observational studies suggest that influenza vaccination may be associated with lower all-cause and CVD mortality and all-cause hospitalization, RCTs reported to date suggest a reduction in the risk of all-cause hospitalization but do not provide clear evidence to support preventive effects on mortality (all-cause or CVD) or CVD hospitalization. [ABSTRACT FROM AUTHOR]

According to recent regulatory guidance, clinical trial objectives should be translated into estimands, i.e., precise descriptions of that what is to be estimated. Hence, estimands are to be formulated for influenza vaccine immunogenicity (IVI) trials, notably for one of the most popular immunogenicity trials, the non-inferiority trial. In this paper an estimand for this trial design is proposed. An estimand should state how intercurrent events are handled. Intercurrent events are events that occur after the start of the trial and that affect the endpoint's measurement or interpretation or prevent its observation. In IVI trials the intercurrent events of interest are immunological intercurrent events (IIEs). Major IIEs are identified, i.e., protocol deviations occurring during the trial that affect immunogenicity endpoints, and the consequences for the trial data collection are discussed. In the statistical analysis endpoint values that are missing or excluded from the analysis due to IIEs are to be substituted by plausible values, by means of multiple imputing. Replacing values are based on predictors of the endpoint. A distinction is made between mandatory and non-mandatory predictors. Mandatory predictors are predictors necessary to prevent biased prediction. Non-mandatory predictors are predictors that limit the additional variance due to the imputing. The four steps of the multiple imputing are explained, and available software is listed. [ABSTRACT FROM AUTHOR]

Study design, and results of the primary efficacy hierarchical endpoints. The win ratio was calculated using an unmatched non-parametric pairwise comparison for each endpoint. The win ratio given as the total number of winner pairs by the total number of the loser pairs. In the present study, a win ratio > 1 indicates benefit of double-dose in-hospital influenza vaccination. [Display omitted] • The first 45 days after an ACS is the period with the more risk for CV events. • Double-dose influenza vaccination following an ACS did not reduce cardiorespiratory. • Similar results were found for only to hierarchical cardiovascular endpoints. • COVID-19 hospitalizations and death did not impact hierarchical endpoints. Influenza vaccination prevents major cardiovascular events in individuals presenting a recent acute coronary syndrome (ACS), however the early effect of an in-hospital double-dose vaccination strategy remains uncertain. The VIP-ACS was a randomized, pragmatic, multicenter, open-label trial with a blinded-adjudication endpoint. Patients with ACS ≤ 7 days of hospitalization were randomized to an in-hospital double-dose quadrivalent inactivated influenza vaccine (double-dose) or a standard-dose influenza vaccine at 30 days post-randomization. The primary endpoint was a hierarchical composite of death, myocardial infarction, stroke, hospitalization for unstable angina, hospitalization for heart failure, urgent coronary revascularization, and hospitalization for respiratory infections, analyzed with the win ratio (WR) method in short-term follow-up (45-days after randomization). The trial enrolled 1,801 patients (≥18 years old). Median participant age was 57 years, 70 % were male. There were no significant differences between groups on the primary hierarchical endpoint: there were 5.7 % wins in the double-dose in-hospital group and 5.5 % wins in the standard-dose delayed vaccination group (WR: 1.03; 95 % CI: 0.70–––1.53; P = 0.85). In a sensitivity analysis including COVID-19 infection in the hospitalizations for respiratory infections endpoint, overall results were maintained (WR: 1.03; 95 % CI 0.71–––1.51; P = 0.87). Results were consistent for major cardiovascular events only (WR: 0.82; 95 % CI: 0.48–––1.39; P = 0.46). No serious adverse events were observed. In patients with recent ACS, in-hospital double-dose influenza vaccination did not significantly reduce cardiorespiratory events at 45 days compared with standard-dose vaccination at 30 days post-randomization. [ABSTRACT FROM AUTHOR]

The first influenza virus infection (imprinting) can lead to long-term immune memory and influence subsequent vaccinations and infections. Previously, we reported a polyethyleneimine (PEI)-Aichi hemagglutinin (HA)/CpG (PHC) nanoparticle with cross-protective potential against homologous and heterologous influenza strains. Here we studied how influenza immune imprinting influences the antibody responses to the PHC vaccination and the protection against heterosubtypic virus challenges. We found that pre-existing virus immunity can maintain or synergize the vaccine-induced antibody titers, depending on the imprinting virus HA phylogenetic group. The HA group 1 virus (PR8, H1N1)-imprinted mice displayed comparable antigen-specific antibody responses to those without imprinting post-PHC vaccination. In contrast, the group 2 virus (Phi, H3N2)-imprinted mice showed significantly more robust and balanced antibodies post-vaccination, conferring complete protection against body weight loss and lung inflammation upon heterosubtypic reassortant A/Shanghai/2/2013 (rSH, H7N9) virus challenge. Our findings suggest that influenza imprinting from the same HA phylogenetic group can synergize subsequent vaccination, conferring heterosubtypic protection. [ABSTRACT FROM AUTHOR]

To investigate trends of influenza vaccine uptake before and during the COVID-19 pandemic in the USA and explore the associated factors. This was a cross-sectional study. Using self-reported data from the National Health Interview Survey during 2014–2021 (response rates ranging from 50.7 to 70.1%), we estimated influenza vaccine uptake. Log-binomial regression models were used to test uptake changes with adjustment for and stratification by demographic and health factors. We included 58,249 children (mean age: 8.7 years; male: 51.1%) and 205,034 adults (mean age: 47.6 years; male: 48.2%). The prevalence ratio (PR) of uptake change comparing the intra- (2020–2021) to the pre-COVID-19 period (2014–2019) was 0.72 among children, with a 10.7% reduction. Uptake changes were found across subgroups, with higher reduction among those aged 0–2 years, non-Hispanic Black and Hispanic ethnicity, from South and West regions, and with lower household income. For adults, uptake increased before and during COVID-19 (PR = 1.15, 95% confidence interval [CI]: 1.12–1.18) but a 2.3% reduction was found among healthcare personnel (PR = 0.95, 95% CI: 0.90–0.997). Influenza vaccination decreased during the COVID-19 pandemic among children and healthcare personnel. Structure inequality to influenza vaccination warrants measures to improve vaccine uptake among vulnerable groups. [ABSTRACT FROM AUTHOR]

COVID-19 vaccination is a key approach to reduce morbidity and mortality in pregnant patients and their newborns. Anti-vaccine sentiment has recently increased with unclear impact on pregnant patients. We examined the association between acceptance of tetanus-diphtheria-acellular pertussis (Tdap) and influenza vaccines, considered to be routine pregnancy vaccines, and COVID-19 vaccine acceptance. Secondarily, we identified other predictors of COVID-19 vaccine uptake and described pregnancy outcomes in patients who were and were not vaccinated during pregnancy. A retrospective cohort study of all patients who delivered at a single site from December 2020 - March 2022. Demographic, pregnancy, neonatal, and vaccination data were abstracted from the electronic medical record, which imports vaccine history from the California Immunization Registry. The relationship between influenza and Tdap vaccine acceptance, other baseline characteristics, and COVID-19 vaccine uptake was assessed using univariable and multivariable regression analysis. Of the 7857 patients who delivered during the study period, 4410 (56.1%) accepted the COVID-19 vaccine. Of those who received the COVID-19 vaccine, 3363 (97.6%) and 3049 (88.5%) received influenza and Tdap vaccines, respectively. Patients were more likely to receive the COVID-19 vaccine if they had advanced maternal age, obesity, Asian race, and private insurance. After adjustment for baseline differences, COVID vaccine acceptance was associated with receipt of Tdap (aOR 2.10, 95% CI 1.90–2.33) and influenza vaccines (aOR 2.83, 95% CI 2.55–3.14). There were no differences in preterm birth, low birthweight, and NICU admission between patients who received and did not receive the COVID-19 vaccine. Patients were more likely to accept COVID-19 vaccination if they received Tdap or influenza vaccinations. Older age, obesity, Asian race, and private insurance were independent predictors of vaccine uptake. Disparities in COVID-19 vaccination uptake bear further exploration to guide efforts in equitable and widespread vaccine distribution. • COVID-19 vaccination is recommended for pregnant individuals. • COVID-19 vaccination rates during pregnancy are low. • Pregnant patients who accept Tdap or flu vaccines have higher COVID-19 vaccine rates. • COVID-19 vaccine uptake is lower in young, Black, publicly insured pregnant patients. • COVID-19 vaccination does not increase risk of adverse pregnancy outcomes. [ABSTRACT FROM AUTHOR]

Insufficient adult vaccination coverage rates remain an international challenge. This nationwide study aimed at exploring vaccination coverage and predictors of influenza, pneumococcal, herpes zoster, tetanus, measles, and hepatitis B vaccine uptake, following the recommendations of the National Immunization Program for adults. This was a multicenter, mixed-methods study conducted at 23 primary care units in six different regions of Greece. A pretested questionnaire was administered to three randomly selected adults who visited each practice daily for 30 consecutive working days. Among the 1571 participants, vaccination coverage for influenza in the high-risk groups was 55%, 36% for pneumococcal disease, 12% for herpes zoster (HZ), 21% for tetanus, 33% for measles, and 11% for hepatitis B. Perception of low susceptibility to disease due to good health status, concerns about side-effects and vaccines' efficacy, and mistrust in pharmaceutical companies were among common factors associated with the vaccines uptake. The strongest factor associated with the participants' vaccination status was their doctor's recommendation (odds ratio [95% confidence interval] influenza: 6.06 [4.52–8.14], pneumococcal disease: 15.73 [10.98–22.52], HZ: 17.01 [9.05–31.96], tetanus: 23.93 [16.20–35.35], measles: 33.47 [16.85–66.47], and hepatitis B: 73.92 [17.47–312.74]). Being well-informed about each vaccine was also a predictor of its uptake. Vaccination coverage was suboptimal and especially low in tetanus, HZ, and hepatitis B immunization. Person-centered approach, with provision of appropriate information about vaccines' safety and efficacy, responding to each patient's needs, as well as physicians' strong recommendation for vaccination are considered crucial to advocate against the spread of vaccine misinformation and increase vaccination coverage. [ABSTRACT FROM AUTHOR]

We aimed to determine how municipal subsidies for seasonal influenza vaccines for the elderly affected vaccination coverage and health outcomes and how responses to vaccine prices changed during the COVID-19 pandemic. This ecological study includes 1245 municipalities in Japan between 2019 and 2020. Fixed-effects regression analysis was performed to evaluate the effect of influenza vaccine cost subsidy for people aged 65 years or older on vaccination coverage, all-cause mortality, and influenza-related mortality. The vaccination rate increased when patients' copayments decreased, and reducing the copayment by 1000 Japanese Yen (JPY) was estimated to increase the vaccination rate by 6.3% (95% confidence interval [CI] 4.5–8.2%) in the adjusted model. When examining the additional effect of a zero price compared to a nearly zero price, we found that a zero price increased the immunization rate by 6.4% (95% CI 1.4–11.5%). The effect of copayment on the increase in vaccination coverage was significantly lower during the pandemic than in the pre-pandemic period. The municipal and prefectural analyses found no association between influenza vaccine copayments and all-cause, influenza, or pneumonia mortality. Cost subsidies and the zero-price effect were shown to increase vaccination coverage but were not associated with relevant mortality measures. Although the impact was attenuated under pandemic conditions, cost subsidy effectively increases the vaccination rate. [ABSTRACT FROM AUTHOR]

Patients with lung cancer have a high risk of influenza complications. International guidelines recommend annual influenza vaccination for patients with cancer. Immune checkpoint inhibitors (ICIs) are progressively used to treat lung cancer. Data regarding immunogenicity and safety of influenza vaccine are limited in patients with lung cancer receiving ICIs; therefore, we conducted this single-center, prospective observational study in the Japanese population. Patients with lung cancer receiving ICIs and influenza immunization were enrolled. Blood samples were collected from patients for serum antibody titer measurement pre- and 4 ± 1 weeks post-vaccination. The primary endpoint was seroprotection rate (sP) at 4 ± 1 weeks post-vaccination. The secondary endpoints were geometric mean titer (GMT), mean fold rise, seroresponse rate (sR), seroconversion rate (sC), and immune-related adverse events (irAEs), defined as adverse effects caused by ICI administration, 6 months post-vaccination. Influenza vaccination in the 23 patients included in the immunogenicity analyses significantly increased GMT for all strains, and sP, sR, and sC were 52%–91%, 26%–39%, and 26%–35%, respectively. In the 24 patients included in the safety analyses, 7 (29%) and 5 (21%) patients exhibited systemic and local reactions, respectively. Only one patient (4%) (hypothyroidism, grade 2) showed post-vaccination irAEs. Overall, influenza vaccination in patients with lung cancer receiving ICIs showed acceptable immunogenicity and safety, thus supporting annual influenza vaccination in this population. [ABSTRACT FROM AUTHOR]

Influenza vaccination (IV) aims primarily to protect high-risk groups against severe influenza-associated disease and death. It is recommended in Spain for high-risk groups, including Healthcare workers (HCWs). However, vaccination uptake has been consistently below desirable levels. The objective of this study were to evaluate influenza vaccination coverage using data from the regional vaccination registry, during 2021–2022 season, among HCWs in public hospitals in Autonomous Community of Madrid (CAM) and to explore factors associated with influenza vaccination. We conducted a cross-sectional study using administrative data retrieved from the Regional Department of Health data repositories. A multilevel logistic regression model was designed to estimate Level 1 (individual) and Level 2 (contextual) variables that are associated with HCẂs vaccination. The study population was HCWs from 25 public hospitals in CAM who were active during the period of the influenza 2021–2022 vaccination campaign. The global influenza vaccination coverage (IVC) was 52.1 %. All study Level 1 variables were significantly associated with vaccine uptake. Greater IVC is associated with individual characteristics: female (OR1.14; 95 %CI 1.09–1.19), older age 59–69 years old (OR1.72; 95 %CI 1.60–1.84), born in Spain, medical staff, more than one high-risk condition (OR1.24; 95 %CI 1.10–1.40; respectively) and vaccinated in two previous campaigns (OR25.64; 95 %CI 24.27–27.09). IVC was highest among HCWs celiac disease (65.5 %) followed by diabetes mellitus (65.1 %) and chronic inflammatory disease (64.3 %). The hospital where the study subject worked also showed an effect on the vaccination uptake, although Level 2 variable (hospital complexity) was not positively associated. IVC in HCWs remains suboptimal. These findings may prove useful to tailor strategies to reach specific groups. It is recommended to delve into the identification of factors associated with the HCWs workplace that may have a positive impact on IV. [ABSTRACT FROM AUTHOR]

Barriers and enablers to vaccination of care home (CH) staff should be identified in order to develop interventions to address them that increase uptake and protect residents. We aimed to synthesis the evidence describing the barriers and enablers that affect the influenza vaccination uptake of care home (CH) staff. We searched PubMed, MEDLINE, EMBASE, CINAHL, PsycINFO, AMED, IBSS, SCOPUS to identify quantitative, qualitative or mixed-method studies. Data related to health or social care workers in CHs reported barriers or enablers were extracted and mapped to the Theoretical Domains Framework (TDF); the data within each domain were grouped and categorized into key factors affecting influenza vaccine uptake among CH staff. We screened 4025 studies; 42 studies met our inclusion criteria. Thirty-four (81 %) were surveys. Five theoretical domains were frequently reported as mediators of influenza vaccine uptake: Beliefs about consequences (32 studies), Environmental context and resources (30 studies), Emotions (26 studies), Social influences (25 studies), Knowledge (22 studies). The low acceptance rate of the influenza vaccine among CH staff can be attributed to multiple factors, including insufficient understanding of the vaccine, its efficacy, or misconceptions about the vaccine (knowledge), perceiving the vaccine as ineffective and unsafe (beliefs about consequences), fear of influenza vaccine and its side effects (emotions), and experiencing limited accessibility to the vaccine (environmental context and resources). Interventions aimed at increasing influenza vaccine uptake among CH staff should focus on addressing the barriers identified in this review. These interventions should include components such as enhancing knowledge by providing accurate information about vaccine benefits and safety, addressing negative beliefs by challenging misconceptions, managing concerns and fears through open communication, and improving accessibility to the vaccine through convenient on-site options. This review provides a foundation for the development of tailored Interventions to improve influenza vaccine uptake among CH staff. [ABSTRACT FROM AUTHOR]

• Influenza vaccine effectiveness (VE) varies from season to season and by setting. • VE against laboratory-confirmed influenza was assessed in a hospital setting. • In adults, the overall vaccine effectiveness was 57 %. • 2022/23 season influenza vaccines were moderately effective against severe influenza. The effectiveness of seasonal influenza vaccination (SIV) varies from year to year. Interim estimates of vaccine effectiveness (VE) in outpatient settings have suggested that the 2022/23 northern hemisphere SIV was 54 % effective. The main goal of this study was to measure the 2022/23 SIV VE among Italian adults in a hospital setting. The study adopted a retrospective test-negative case-control design and was conducted in a large tertiary hospital (Genoa, Italy) between October 2022 and April 2023. Adult (≥18 years) patients accessing the hospital's Emergency Department for symptoms ascribable to an acute respiratory infection, for which a reverse-transcription real-time polymerase chain reaction test for the detection of influenza virus was prescribed, were potentially eligible. Of 33,692 referrals assessed, 487 patients were included in the study. A total of 13 % of patients were positive for influenza, most of which (63 %) belonged to the A(H3N2) subtype. SIV VE was 57 % (95 % CI: 11–81 %), 53 % (95 % CI: 2–80 %) and 38 % (95 % CI: −34–74 %) against any influenza, influenza A and A(H3N2), respectively. Although no cases caused by A(H1N1)pdm09 and B strains were observed among vaccinated individuals, VE estimates against the latter were imprecise, owing to their low detection rates. In conclusion, the 2022/23 SIV was moderately effective against hospital encounters for laboratory-confirmed influenza. [ABSTRACT FROM AUTHOR]

Presenting exogenous antigens on virus-like particles (VLPs) through "plug-and-display" decoration strategies based on SpyTag/SpyCatcher isopeptide bonding have emerged as attractive technology for vaccine synthesis. However, whether the position of ligation site in VLPs will impose effects on immunogenicity and physiochemical properties of the synthetic vaccine remains rarely investigated. Here in the present work, the well-established hepatitis B core (HBc) protein was used as chassis to construct dual-antigen influenza nanovaccines, with the conserved epitope peptides derived from extracellular domain of matrix protein M2 (M2e) and hemagglutinin (HA) as target antigens. The M2e antigen was genetically fused to the HBc in the MIR region, together with the SpyTag peptide, which was fused either in the MIR region or at the N-terminal of the protein, so that a recombinant HA antigen (rHA) linked to SpyCatcher can be displayed on it, at two different localizations. Both synthetic nanovaccines showed ability in inducing strong M2e and rHA-specific antibodies and cellular immunogenicity; nevertheless, the one in which rHA was conjugated by N-terminal Tag ligation, was superior to another one synthesized by linking the rHA to MIR region SpyTagged-HBc in all aspects, including higher antigen-specific immunogenicity responses, lower anti-HBc carrier antibody, as well as better dispersion stability. Surface charge and hydrophobicity properties of the two synthetic nanovaccines were analyzed, results revealed that linking the rHA to MIR region SpyTagged-HBc lead to more significant and disadvantageous alteration in physiochemical properties of the HBc chassis. This study will expand our knowledge on "plug-and-display" decoration strategies and provide helpful guidance for the rational design of HBc-VLPs based modular vaccines by using SpyTag/Catcher synthesis. [ABSTRACT FROM AUTHOR]

The prevention of serious influenza-related severe conditions due to influenza is important, particularly in elderly patients, age is a risk factor for death resulting from influenza-related respiratory diseases. The aim of the present study was to investigate the association of influenza vaccination with severe condition requiring critical care and death in elderly people, using vaccine records and healthcare administrative claims data in a Japanese city. Among 5608 patients aged ≥65 years diagnosed with influenza, we identified 96 patients who had received invasive mechanical ventilation or died. Thereafter, we matched 384 controls with the cases. The cases were less vaccinated than the controls (37.5% vs. 56.0%, P < 0.01). In the multivariate analysis, influenza vaccination was associated with a lower proportion of the composite outcome (odds ratio, 0.35; 95% confidence interval, 0.21–0.60). In patients aged ≥80 years old and those with cardiovascular disease, influenza vaccination was associated with low composite outcomes. Influenza vaccination was associated with reduced proportions of receiving invasive mechanical ventilation or influenza-related mortality, particularly in those aged ≥80 years old. [ABSTRACT FROM AUTHOR]

In order to better define the need for influenza vaccination in people with diabetes (DM), we collected all available evidence on the effect of DM as a risk factor for complications of both seasonal and pandemic influenza, and on the specific effectiveness of vaccines in patients with DM. Two distinct systematic searches on MEDLINE, Cochrane, ClinicalTrials.gov and Embase databases were performed, one for each metanalysis, collecting all observational studies and randomized clinical trials performed on humans up to May 31st, 2022. We retrieved 34 observational studies comparing risk for influenza complications in people with or without diabetes, and 13 observational studies assessing vaccine effectiveness on preventing such complications. Mortality for influenza and hospitalization for influenza and pneumonia resulted significantly higher in individuals with versus without DM, both when unadjusted and adjusted data are analyzed. In diabetic individuals vaccinated for influenza overall hospitalization, hospitalization for influenza or pneumonia and overall mortality are significantly lower in comparison with not vaccinated DM subjects, both when unadjusted and adjusted data were analyzed. This systematic review and meta-analysis shows that: 1) influenza is associated with more severe complications in diabetic versus not diabetic individuals and 2) influenza vaccination is effective in preventing clinically relevant outcomes in adults with DM with a NNT (number needed to treat) of 60, 319, and 250 for all-cause hospitalization, specific hospitalization, and all-cause mortality, respectively. The identification of diabetic patients as the target of vaccination campaigns for influenza appears to be justified by available clinical evidence. [ABSTRACT FROM AUTHOR]

The continuing evolution of influenza viruses poses a challenge to vaccine prevention, highlighting the need for a universal influenza vaccine. We evaluated the safety and immunogenicity of one such candidate, Multimeric-001 (M-001), when used as a priming vaccine prior to administration of quadrivalent inactivated influenza vaccine (IIV4). Healthy adults 18 to 49 years of age were enrolled in a phase 2 randomized, double-blind placebo-controlled trial. Participants received two doses of either 1.0-mg M-001 or saline placebo (60 per study arm) on Days 1 and 22 followed by a single dose of IIV4 on about Day 172. Safety, reactogenicity, cellular immune responses and influenza hemagglutination inhibition (HAI) and microneutralization (MN) were assessed. The M-001 vaccine was safe and had an acceptable reactogenicity profile. Injection site tenderness (39% post-dose 1, 29% post-dose 2) was the most common reaction after M-001 administration. Polyfunctional CD4+ T cell responses (perforin-negative, CD107α-negative, TNF-α+, IFN-γ+, with or without IL-2) to the pool of M-001 peptides increased significantly from baseline to two weeks after the second dose of M-001, and this increase persisted through Day 172. However, there was no enhancement of HAI or MN antibody responses among M-001 recipients following IIV4 administration. M-001 administration induced a subset of polyfunctional CD4+ T cells that persisted through 6 months of follow-up, but it did not improve HAI or MN antibody responses to IIV4. (clinicaltrials.gov NCT03058692). [ABSTRACT FROM AUTHOR]

• Provide a framework that can be used to identify the surrogate effect in a randomized trial. • Propose instrumental variable analyses with randomized vaccination as an IV accounting for potential unmeasured confounding. • Postvaccination HAI titer is an important surrogate of protection from influenza virus infection. Immune correlate analyses for vaccine trials have been applied to investigate associations of vaccine efficacy and surrogate markers such as vaccine-induced antibodies. However, the role of antibody as a surrogate marker in predicting the outcome can vary by time, and surrogate-outcome confounding may have resulted in bias even in randomized trials. We provide a framework for surrogate marker assessment to address the aforementioned issues. We reanalyzed the vaccine randomized trial for influenza B. We conducted a mediation analysis that enables estimation of vaccine efficacy, mediation effects and proportion of mediation on disease probabilities at various follow-up times. We proposed instrumental variable (IV) analyses with randomized vaccination as an IV accounting for potential unmeasured confounding. The mediation effect of vaccine efficacy by hemagglutination inhibition (HAI) titer was significantly protective at 181 days after vaccination: 63.2% [95% confidence interval, (CI) = (39.9%, 82.0%)], and HAI titer explained 61.1% [95% CI = (36.7%, 96.2%)] of the protective effect of vaccination. Most of vaccine efficacy is mediated by HAI titer, particularly in children 10 years and older. Our contribution is to provide causal analytics for the role of surrogate marker with weaker assumptions regarding surrogate–disease causation. [ABSTRACT FROM AUTHOR]

Immunizations for influenza and pneumococcus are effective interventions in reducing morbidity and mortality. The objective of this study was to describe the vaccination rates in volunteers from three regions of Argentina during the COVID-19 pandemic. In 2020, 3853 adults were surveyed, 61.6 % were females, 45 % were aged between 40 and 60 and 18.6 % were > 60 years old. The commonest comorbidities were hypertension (12.9 %), dyslipidemia (8.5 %), and smokers or former smokers (9.2 %). The global influenza vaccination rate was 37.7 %, pneumococcal vaccination 24.7 %, and both 17.8 %. Multivariable regression showed that the vaccination rate increased with age and the presence of comorbidities. However, in the subgroup with indications for both vaccines, 71.7 % had the influenza vaccine, 59 % had the pneumococcal vaccine, and 28.3 % received neither. Our study suggests that influenza and pneumococcal vaccine percentages in high-risk patients in Argentina remain sub-optimal. Immunizations with proven reductions in morbimortality could have also been relegated during the COVID pandemic. [ABSTRACT FROM AUTHOR]

• When delivered by VaxiPatch, a 2 µg dose of Flucelvax was comparable to IM injection. • Co-formulation of a low-dose AS01 B -like adjuvant enhanced VaxiPatch responses. • Even for adjuvanted groups, reactogenicity from patch application was negligible. • Vaccine antigens were dramatically stabilized against heat stress on VaxiPatch. 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 AS01 B , 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. [ABSTRACT FROM AUTHOR]

In the study, the adjuvant features of the immunoregulatory polysaccharide component CARP2 isolated from cultivated Artemisia rupestris L. for influenza virus vaccine (IVV) and the mechanism responsible for its action in DCs were further explored. CARP2 showed a typical absorbance peak of polysaccharides in spectral analysis. At two doses of CARP2-adjuvanted IVV, IgG, hemagglutination inhibition (HI) titers, and effector/memory T cells were generated and lasted for 275 days without adverse events. CARP2 primed rapid HI and IgG, IgG2a/IgG1 ratio, splenocyte proliferation, and cytotoxic T lymphocyte (CTL), and facilitated the generation of INF-γ and IL-4 by activating DCs and regulatory T cells (Tregs). Additionally, CARP2 achieved the ten-fold dose-sparing effect. In vitro, CARP2 stimulated DCs to prime the production of Th1/Th2 cytokines and CCR7 and activated MyD88-dependent pathway by upregulating the expressions of TLR4, MyD88, TRAF-6, and p65. In contrast, MyD88, TRAF-6, and NF-κB inhibitors partially blocked the effect through reducing related cytokines and proteins. Overall, CARP2 promoted IVV efficacy, which was involved in the modulation of Th1/Th2 responses and shifted toward Th1-polarizing response via TLR4/MyD88/TRAF/NF-κB activation in DCs. [Display omitted] • CARP2 improved IVV efficacy with dose-sparing and long-term effects. • CARP2 triggered Th1/Th2 responses and shifted toward Th1-polarizing response. • CARP2 activated DCs through TLR4/MyD88/TRAF/NF-κB pathways. • CARP2 may be utilized as a potential polysaccharide adjuvant for IVV. [ABSTRACT FROM AUTHOR]

L'érythème pigmenté fixe bulleux généralisé est une variante de l'érythème pigmenté fixe qui peut se manifester dans de rares cas. C'est une toxidermie sévère d'origine médicamenteuse nécessitant une prise en charge spécialisée. Peu de cas d'érythème pigmenté fixe bulleux généralisé imputables au vaccin grippal sont décrit dans la littérature, nous rapportons un nouveau cas d'érythème pigmenté fixe bulleux généralisé induit par le vaccin de la grippe. Il s'agit d'une patiente de 58 ans présentant un érythème pigmenté fixe bulleux survenant trois jours après la vaccination contre la grippe. La patiente ne recevait aucun traitement pouvant expliquer la symptomatologie clinique. La biopsie cutanée a montré des kératinocytes apoptotiques dans l'épiderme avec un début de clivage sous-épidermique. L'érythème pigmenté fixe est une toxidermie courante aux médicaments, caractérisée par des plaques érythémateuses arrondies, uniques ou multiples, cédant la place à des macules hyper-pigmentées cicatricielles. Elle réapparaît sur les mêmes sites cutanés ou muqueux, avec la possibilité d'apparition d'autres plaques, chaque fois que l'agent incriminé est réintroduit. Les médicaments les plus fréquemment incriminés sont les anti-inflammatoires non stéroïdiens, les antibiotiques et les antiépileptiques. L'érythème pigmenté fixe bulleux généralisé est une variante rare de l'érythème pigmenté fixe. Seuls quelques cas ont été rapportés suite à l'administration du vaccin annuel contre la grippe. Le diagnostic différentiel inclut le syndrome de Stevens-Johnson et la nécroépidermolyse toxique dans lesquels les lésions apparaissent au bout de 1 à 4 semaines après la prise du médicament et touchent presque toujours les muqueuses, avec une atteinte systémique marquée. Bien que l'érythème pigmenté fixe bulleux généralisé soit moins grave que ces syndromes, il peut s'avérer potentiellement mortel, surtout chez les sujets âgés. L'érythème pigmenté fixe bulleux généralisé est une entité rare de l'érythème pigmenté fixe, souvent confondu avec les dermatoses bulleuses et les toxidermies graves. Les médicaments incriminés sont nombreux, mais peu de cas d'érythème pigmenté fixe bulleux généralisé suivant une vaccination contre la grippe ont été rapportés. Generalized bullous fixed drug eruption is a variant of fixed drug eruption occurring in rare cases. It is a severe drug-induced eruption requiring special management. Few cases of generalized bullous fixed drug eruption occurring after the influenza vaccine have been described in the literature, we report a new case of generalized bullous fixed drug eruption occurring after the influenza vaccine. The patient is a 58-year-old female patient with generalized bullous fixed drug eruption occurring three days after the influenza shot. The patient did not receive any treatment that could potentially cause the clinical symptomatology. Skin biopsy showed apoptotic keratinocytes in the epidermis with the onset of subepidermal cleavage. Fixed drug eruption is a common drug eruption characterized by single or multiple rounded erythematous plaques giving way to scarring hyperpigmented macules. It recurs on the same cutaneous or mucosal sites, with the possibility of the appearance of other plaques, each time the incriminated agent is taken. The most commonly incriminated drugs are non-steroidal anti-inflammatory drugs, antibiotics and anti-epileptic drugs. Generalized bullous fixed drug eruption is a rare variant of fixed drug eruption, with only a few cases reported following the annual flu vaccine. The differential diagnosis includes Stevens-Johnson syndrome and toxic epidermal necrolysis in which lesions appear within 1 to 4 weeks of drug administration and almost always involve mucous membranes with marked systemic involvement. Although generalized bullous fixed drug eruption is less severe than these syndromes, it can be potentially fatal, especially in elderly subjects. Generalized bullous fixed drug eruption is a rare entity of fixed drug eruption, often confused with bullous dermatoses and severe drug eruptions such as Stevens-Johnson syndrome and toxic epidermal necrolysis. The drugs involved are numerous, but few cases of generalized bullous fixed drug eruption following the influenza vaccination have been reported. [ABSTRACT FROM AUTHOR]

Due to the higher risk of medical complications posed by influenza infection, patients with type 1 diabetes (T1D) are strongly recommended to receive the influenza vaccine. However, it remains unclear if hyperglycemia in patients with T1D affects vaccine-induced immune responses. In this study, we investigated the humoral and cellular immune responses of prediabetic and diabetic, nonobese diabetic (NOD) mice following influenza vaccination to determine the effects of hyperglycemia on influenza vaccine-induced responses. In diabetic NOD mice, vaccine-specific IgG and IgM levels, as well as IgG-producing cells, were comparable to those in prediabetic NOD mice. However, the diabetic NOD mice exhibited reduced percentages of memory T cells and activated T cells in the spleen, along with reduced number of vaccine-specific interferon (IFN)-γ-secreting cells. Thus, these findings suggest that in patients with T1D, hyperglycemia could lead to impaired cell-mediated immune responses following influenza vaccination. [ABSTRACT FROM AUTHOR]

Despite a longstanding Israel Ministry of Health recommendation that all healthcare personnel (HCP) receive a seasonal influenza vaccine, vaccine uptake among HCP remains below the country's target of 60% coverage. To understand factors related to vaccine hesitancy, we used data from a prospective three-year (2016–2019) influenza vaccine effectiveness study among Israeli HCP to examine knowledge, attitudes, and practices (KAP) about influenza vaccination and their association with vaccine uptake. At the start of each influenza season, all participating HCP completed a questionnaire that included questions about socio-demographic and occupational characteristics, health status, and KAP related to seasonal influenza vaccination. We extracted vaccination history from electronic medical records and employee vaccination registries. We used logistic regression models to identify demographic and occupational factors, and KAP about influenza vaccination, associated with receipt of vaccination. A total of 2,126 HCP were enrolled and had available data on vaccination history. Their median age was 42 years [IQR 35–52], and 73 % self-identified as female. Influenza vaccine uptake in 2016, 2017 and 2018 was 46 %, 48 % and 47 %, respectively. Overall, 36 % of HCP had received an influenza vaccine in ≥ 4 of the eight years prior. HCP aged 35–49 years were less likely to receive influenza vaccine compared to HCP aged ≥ 50 years (OR: 0.81 [95 % CI: 0.67–0.98]). Nurses and allied personnel were less likely to receive influenza vaccine compared to physicians (OR: 0.63 [95 % CI: 0.50–0.78] and OR: 0.53 [95 % CI: 0.40–0.70], respectively). The emotional benefit of vaccination (e.g., anticipating regret if not vaccinated) and the perception of vaccine safety were factors associated with vaccine uptake (OR: 7.60 [95 % CI: 6.27–9.22] and OR: 3.43 [95 % CI:2.91–4.03], respectively). Among HCP at two hospitals in Israel, less than half received an annual influenza vaccine. Older HCP, physicians, and those who reported the emotional benefit of vaccination or agreed that influenza vaccines are safe were more likely to be vaccinated. Future influenza vaccination campaigns could focus on these demographic groups and tailor messages emphasizing the emotional benefits of vaccination and vaccine safety to increase seasonal influenza vaccine uptake among HCP in Israel. [ABSTRACT FROM AUTHOR]

Estimating the burden of disease averted by vaccination can assist policymakers to implement, adjust, and communicate the value of vaccination programs. Demonstrating the use of a newly available modeling tool, we estimated the burden of influenza illnesses averted by seasonal influenza vaccination in El Salvador, Panama, and Peru during 2011–2018 among two influenza vaccine target populations: children aged 6–23 months and pregnant women. We derived model inputs, including incidence, vaccine coverage, vaccine effectiveness, and multipliers from publicly available country-level influenza surveillance data and cohort studies. We also estimated changes in illnesses averted when countries' vaccine coverage was achieved using four different vaccine deployment strategies. Among children aged 6–23 months, influenza vaccination averted an estimated cumulative 2,161 hospitalizations, 81,907 medically-attended illnesses, and 126,987 overall illnesses during the study period, with a prevented fraction ranging from 0.3 % to 12.5 %. Among pregnant women, influenza vaccination averted an estimated cumulative 173 hospitalizations, 6,122 medically attended illnesses, and 16,412 overall illnesses, with a prevented fraction ranging from 0.2 % to 10.9 %. Compared to an influenza vaccine campaign with equal vaccine distribution during March—June, scenarios in which total cumulative coverage was achieved in March and April consistently resulted in the greatest increase in averted illness (23 %-3,129 % increase among young children and 22 %-3,260 % increase among pregnant women). Influenza vaccination campaigns in El Salvador, Panama, and Peru conducted between 2011 and 2018 prevented hundreds to thousands of influenza-associated hospitalizations and illnesses in young children and pregnant women. Existing vaccination programs could prevent additional illnesses, using the same number of vaccines, by achieving the highest possible coverage within the first two months of an influenza vaccine campaign. [ABSTRACT FROM AUTHOR]

During November 2019–October 2021, a pediatric influenza vaccination demonstration project was conducted in four sub-counties in Kenya. The demonstration piloted two different delivery strategies: year-round vaccination and a four-month vaccination campaign. Our objective was to compare the costs of both delivery strategies. Cost data were collected using standardized questionnaires and extracted from government and project accounting records. We reported total costs and costs per vaccine dose administered by delivery strategy from the Kenyan government perspective in 2021 US$. Costs were separated into financial costs (monetary expenditures) and economic costs (financial costs plus the value of existing resources). We also separated costs by administrative level (national, regional, county, sub-county, and health facility) and program activity (advocacy and social mobilization; training; distribution, storage, and waste management; service delivery; monitoring; and supervision). The total estimated cost of the pediatric influenza demonstration project was US$ 225,269 (financial) and US$ 326,691 (economic) for the year-round delivery strategy (30,397 vaccine doses administered), compared with US$ 214,753 (financial) and US$ 242,385 (economic) for the campaign strategy (25,404 doses administered). Vaccine purchase represented the largest proportion of costs for both strategies. Excluding vaccine purchase, the cost per dose administered was US$ 1.58 (financial) and US$ 5.84 (economic) for the year-round strategy and US$ 2.89 (financial) and US$ 4.56 (economic) for the campaign strategy. The financial cost per dose was 83% higher for the campaign strategy than the year-round strategy due to larger expenditures for advocacy and social mobilization, training, and hiring of surge staff for service delivery. However, the economic cost per dose was more comparable for both strategies (year-round 22% higher than campaign), balanced by higher costs of operating equipment and monitoring activities for the year-round strategy. These delivery cost data provide real-world evidence to inform pediatric influenza vaccine introduction in Kenya. [ABSTRACT FROM AUTHOR]

In 2016, the Kenya National Immunization Technical Advisory Group requested additional programmatic and cost effectiveness data to inform the choice of strategy for a national influenza vaccination program among children aged 6–23 months of age. In response, we conducted an influenza vaccine demonstration project to compare the performance of a year-round versus campaign-mode vaccination strategy. Findings from this demonstration project will help identify essential learning lessons for a national program. We compared two vaccine delivery strategies: (i) a year-round vaccination strategy where influenza vaccines were administered throughout the year at health facilities. This strategy was implemented in Njoro sub-county in Nakuru (November 2019 to October 2021) and Jomvu sub-county in Mombasa (December 2019 to October 2021), (ii) a campaign-mode vaccination strategy where vaccines were available at health facilities over four months. This strategy was implemented in Nakuru North sub-county in Nakuru (June to September 2021) and Likoni sub-county in Mombasa (July to October 2021). We assessed differences in coverage, dropout rates, vaccine wastage, and operational needs. We observed similar performance between strategies in coverage of the first dose of influenza vaccine (year-round strategy 59.7 %, campaign strategy 63.2 %). The coverage obtained in the year-round sub-counties was similar (Njoro 57.4 %; Jomvu 63.1 %); however, more marked differences between campaign sub-counties were observed (Nakuru North 73.4 %; Likoni 55.2 %). The campaign-mode strategy exceeded the cold chain capacity of participating health facilities, requiring thrice monthly instead of once monthly deliveries, and was associated with a two-fold increase in workload compared to the year-round strategy (168 vaccines administered per day in the campaign strategy versus 83 vaccines administered per day in the year-round strategy). Although both strategies had similar coverage levels, the campaign-mode strategy was associated with considerable operational needs that could significantly impact the immunization program. [ABSTRACT FROM AUTHOR]

Reactivation of the latent varicella-zoster virus can cause herpes zoster (HZ) infection, and renal transplant recipients undergoing immunosuppressive therapy are particularly susceptible to this condition. This study aims to evaluate the potential increase in HZ incidence following influenza vaccination among this specific patient population. This study was a population-based, retrospective, self-controlled case series. Data were retrieved from Taiwan's National Health Insurance Research Database spanning the years 2008 to 2017. Patients diagnosed with HZ within a 6-month period before and after receiving the influenza vaccine were eligible for inclusion. Two distinct time intervals were defined for analysis: the initial 15 days and 30 days following vaccination were categorized as risk intervals, while all other periods served as control intervals. Incidence rate ratios (IRRs) were computed to compare HZ incidence during the risk intervals with that during the control intervals. This study encompassed a cohort of 4,222 renal transplant recipients who had received the influenza vaccine. Among this group, 67 recipients were subsequently diagnosed with HZ. The IRR during both the initial 15 days (IRR = 0.63; 95 % CI, 0.23–1.89) and the first 30 days (IRR = 1.50; 95 % CI, 0.71–3.16) following influenza vaccination did not demonstrate a statistically significant increase when compared to the post-exposure observation times. Comparable results were also observed when comparing these IRR values to the pre-exposure observation times. The subgroup analysis, stratified by age, sex, and underlying medical conditions (including cancer and autoimmune diseases), revealed that the IRRs did not exhibit statistically significant differences. No significant association between the influenza vaccine and an elevated risk of HZ was detected. The administration of annual influenza vaccines appears to be a reasonable practice for renal transplant recipients. [ABSTRACT FROM AUTHOR]

• Influenza vaccine effectiveness was assessed in a large hospital setting. • The 2023/2024 season in Italy was dominated by influenza A(H1N1)pdm09. • In older adults, a moderate vaccine effectiveness was of 51% was observed. • In older adults, enhanced influenza vaccines may provide better protection. In order to support policymakers in allocating resources, we aimed to assess vaccine effectiveness (VE) of inactivated influenza vaccines (IIVs) available for Italian adults in the 2023/2024 season. A hospital-based test-negative case-control study was conducted in Genoa between mid-October 2023 and mid-April 2024. Adult (≥18 years) inpatients with prescription of a polymerase chain reaction test for influenza were eligible. Of 1,664 adults analyzed, most (82%) of which were ≥65 years, 114 (6.9%) tested positive for influenza A. Most (92%) cases were caused by subclades 6B.1A.5a.2a and 6B.1A.5a.2a.1 of the A(H1N1)pdm09 subtype. In older adults aged ≥65 years vaccination was effective at 51% (95% CI: 8%, 74%) against any influenza A and 49% (95% CI: 2%, 73%) against A(H1N1)pdm09. Compared with non-vaccinated older adults, VE point estimates for the adjuvanted and, especially, high-dose IIVs were higher than those for the standard-dose non-adjuvanted IIV. The 2023/2024 seasonal influenza vaccination proved moderately effective in preventing hospitalization for laboratory-confirmed influenza. Being more appropriate for older adults, local policymakers and vaccinating physicians should maximize adoption of the enhanced IIVs. [ABSTRACT FROM AUTHOR]

Globally, influenza poses a substantial threat to public health, serving as a major contributor to both morbidity and mortality. The current vaccines for seasonal influenza are not optimal. A novel recombinant hemagglutinin (rHA) protein-based quadrivalent seasonal influenza vaccine, SCVC101, has been developed. SCVC101-S contains standard dose protein (15μg of rHA per virus strain) and an oil-in-water adjuvant, CD-A, which enhances the immunogenicity and cross-protection of the vaccine. Preclinical studies in mice, rats, and rhesus macaques demonstrate that SCVC101-S induces robust humoral and cellular immune responses, surpassing those induced by commercially available vaccines. Notably, a single injection with SCVC101-S can induce a strong immune response in macaques, suggesting the potential for a standard-dose vaccination with a recombinant protein influenza vaccine. Furthermore, SCVC101-S induces cross-protection immune responses against heterologous viral strains, indicating broader protection than current vaccines. In conclusion, SCVC101-S has demonstrated safety and efficacy in preclinical settings and warrants further investigation in human clinical trials. Its potential as a valuable addition to the vaccines against seasonal influenza, particularly for the elderly population, is promising. [ABSTRACT FROM AUTHOR]

• Experiment focused on vaccine-hesitant parents of children aged 6 months − 18 years. • Study examined if altruism educational intervention could improve parental attitude. • Intervention correlated with decreased vaccine hesitancy, improved vaccine uptake. • Altruism-tailored intervention improved attitudes in vaccine-hesitant parents. A prospective, single-arm clinical trial was conducted to evaluate an altruism-tailored educational intervention to improve parental attitudes and vaccine uptake in vaccine-hesitant parents. Vaccine-hesitant parents at two primary care sites, spanning two influenza seasons from 2020 to 2021 were provided an intervention (spoken and written communication) which highlighted altruistic benefits of accepting the seasonal influenza vaccine to optimize herd immunity to help protect pediatric cancer patients. Eligible parents included those with children eligible for the seasonal influenza vaccine, those who were proficient in English, and those with scores on the adjusted Vaccine Hesitancy Scale (aVHS) suggesting vaccine hesitancy (score ≥ 3). Enrollees completed a demographic questionnaire, underwent the educational intervention, and repeated the aVHS. Vaccination status at that visit was assessed. The primary outcome was change in aVHS scores obtained pre- and post-intervention. Influenza vaccine acceptance, along with demographic information, were also analyzed. We enrolled 510 parents of influenza vaccine eligible children and identified 73 vaccine-hesitant parents. There was an overall trend toward lower aVHS score, with a mean change in hesitancy score of −0.4 (P < 0.01). 43/73 (58.9 %) of the cohort experienced a positive effect toward a lower aVHS score, and 27/73 (37.0 %) of vaccine hesitant subjects became non-hesitant on the aVHS. Several demographic characteristics were associated with vaccine hesitancy in the screening population: educational level lower than bachelor's degree (p = 0.03), household income < 400 % of federal poverty level (p < 0.01), unmarried (p = 0.02), and identifying with a political affiliation other than Democrat (p < 0.01). However, no demographic characteristics were significantly associated with an individual becoming non-hesitant. Our altruism-tailored communication approach carried the largest positive impact on the altruism-specific question on the aVHS, decreasing the post-intervention response value by nearly 25 % (P < 0.01). Our altruism-tailored communication approach significantly improved attitudes regarding childhood influenza vaccine among vaccine-hesitant parents. ClinicalTrials.gov Identifier : NCT04568590. [ABSTRACT FROM AUTHOR]

• Continuous evaluation of the effectiveness of pneumococcal vaccine in adults is crucial. • Childhood PCV immunization, especially PCV13, leads to serotype replacement and herd immunity. • The effectiveness of PPSV23 may change. • We examined the effectiveness of PPSV23 against pneumonia in the Japanese elderly. • PPSV23 is not effective against all-cause and pneumococcal pneumonia in the elderly. In the era of childhood pneumococcal conjugate vaccine (PCV) immunization, especially 13-valent pneumococcal conjugate vaccine (PCV13) immunization, serotype replacement of Streptococcus pneumoniae and herd immunity in adults have been reported worldwide. Therefore, continuous evaluation of the effectiveness of the pneumococcal vaccine in adults is crucial because vaccine effectiveness may change owing to these factors. The purpose of this study was to evaluate the effectiveness of the 23-valent pneumococcal polysaccharide vaccine (PPSV23) against all-cause pneumonia and pneumococcal pneumonia in older individuals with community-acquired pneumonia (CAP) after the introduction of childhood PCV13 in Japan, a topic that has remained largely unexplored. We evaluated pneumococcal vaccine effectiveness in this multicenter, matched case-control study conducted in hospitals and clinics. Cases included patients (aged ≥ 65 years) newly diagnosed with CAP between October 2016 and September 2019. A maximum of five non-pneumonia control patients matched for sex, school grade, date of outpatient visit, and medical institution were selected for each case. Conditional logistic regression models were used to calculate the odds ratios (ORs) and 95% confidence intervals (CIs) of pneumococcal vaccines for the occurrence of all-cause CAP and pneumococcal CAP. The analysis included 740 individuals (142 patients and 598 controls). The median age of participants was 75 years (men: 54%). The adjusted OR for pneumococcal vaccination against all-cause CAP was 1.31 (95% CI: 0.84–2.06), while that for PPSV23 vaccination in the previous 5 years was 1.33 (95% CI: 0.85–2.09). The adjusted OR for PPSV23 vaccination in the previous 5 years against pneumococcal CAP was 0.93 (95% CI: 0.35–2.50). This study was unable to demonstrate the effectiveness of PPSV23 against all-cause and pneumococcal pneumonia after the introduction of childhood PCV13 in Japan. Nonetheless, additional studies are needed to validate these results. [ABSTRACT FROM AUTHOR]

• Influenza vaccine prevent mortality due to influenza, but coverage remain low. • A road map was developed to scale up vaccine coverage in Eastern Mediterranean Region. • Countries were categorised into three group to develop targeted strategies. • Countries with weak influenza programs should strengthen vaccination programme. • Countries with established influenza programs should improve coverage. The aim of this project was to develop a road map to support countries in Eastern Mediterranean Region in developing and implementing evidence-based seasonal influenza vaccination policy, strengthen influenza vaccination delivery program and address vaccine misperceptions and hesitancy. The road map was developed through consultative meetings with countries' focal points, review of relevant literature and policy documents and analysis of WHO/UNICEF Joint Reporting Form on immunization ((JRF 2015–2020) data. Countries were categorised into three groups, based on the existence of influenza vaccination policy and national regulatory authority, availability of influenza vaccine in the country and number of influenza vaccine doses distributed/ 1000 population. The final road map was shared with representatives of all countries in Eastern Mediterranean Region and other stakeholders during a meeting in September 2021. The goal for next 5 years is to increase access to and use of utilization of seasonal influenza vaccine in Eastern Mediterranean Region to reduce influenza-associated morbidity and mortality among priority groups for vaccination. Countries in the Eastern Mediterranean Region are at different stages of implementation of the influenza vaccination program, so activities are planned under four strategic priority areas based on current situations in countries. The consultative body recommended that some countries should establish a new seasonal influenza vaccination programme and ensure the availability of vaccines, while other countries need to reduce vaccine hesitancy and enhance current seasonal influenza vaccination coverage, particularly in all high-risk groups. Countries are also encouraged to leverage COVID-19 adult vaccination programs to improve seasonal influenza vaccine uptake. This road map was developed through a consultative process to scale up the uptake and utilization of influenza vaccine in all countries of Eastern Mediterranean Region. The road map proposes activities that should be adopted in the local context to develop/ update national policies and programs. [ABSTRACT FROM AUTHOR]

• This is the first report of the co-administration of CoronaVac with IIV4 in adults aged 18–59 years. • The occurrence of adverse reactions (AR) in all groups was no more than 20% and 98.9% of the ARs were mild or moderate. • Both concomitant or separate administration of CoronaVac and IIV4 could induce sufficient immunogenicity. • A slight interference with the immune response to CoronaVac was observed in participants in C2 subgroup. • At least two doses of CoronaVac are needed to fulfill the primary immunization of inactivated COVID-19 vaccine. Studies are needed for evidence of inactivated COVID-19 vaccine co-administered with influenza vaccine. A randomized, open-label, controlled study was conducted in Zhejiang Province, China. Eligible healthy adults aged 18–59 years underwent randomization at a ratio of 1:1:2 to receive inactivated quadrivalent influenza vaccine (IIV4) either concomitantly with the first (C1 subgroup) or the second (C2 subgroup) dose of CoronaVac, or 14 days after the first dose of CoronaVac (S group). The primary purpose of the study was to prove the non-inferiority in seroconversion rate of antibody against SARS-CoV-2. Overall, 480 participants were enrolled, with 120, 120, and 240 randomly assigned to the C1, C2, and S groups, respectively. As lower bound of the two-sided 95% confidence interval (CI) of the difference for the seroconversion rate of antibodies against SARS-CoV-2 was over −10%, the immune response for CoronaVac in the C group (93.1% [89.0, 96.0]) was non-inferior to that in the S group (95.2% [91.5, 97.6]) in the per-protocol set. A lower GMT of antibody against SARS-CoV-2 was observed in the C group as compared to the S group (27.5 vs. 38.1, P = 0.0001). Decrease of immune response to CoronaVac was mainly observed in participants received IIV4 concomitantly with their second dose of CoronaVac (C2 subgroup), with a seroconversion rate of 89.7% (95CI: 82.6%-94.5%) and a GMT of 23.3. The occurrences of vaccine related adverse reactions were no more than 20% and comparable among different groups. Most of the adverse reactions were mild and moderate. Co-administration of inactivated COVID-19 vaccine and seasonal influenza vaccine, especially the administration regimen that the seasonal influenza vaccine co-administered with the first dose of the inactivated COVID-19 vaccine, would be feasible. [ABSTRACT FROM AUTHOR]

• The trial vaccine was safe in subjects ≥ 3 years. • The immunogenicity of trial vaccine was non-inferior to the comparator in ≥ 3 years subjects. • Two-dose vaccine series with the trial vaccine is safe and can trigger a stronger immune response than that of one-dose in 3–8 years subjects. Subunit influenza vaccine only formulated with surface antigen proteins has better safety profiles relative to split-virion influenza vaccine. Compared to the traditional quadrivalent split-virion influenza vaccine, a novel quadrivalent subunit influenza vaccine is urgently needed in China. We completed a phase 3, randomized, double-blind, active-controlled, non-inferiority clinical study at two sites in Henan Province, China. Eligible volunteers were split into four age cohorts (3–8 years, 9–17 years, 18–64 years, and ≥ 65 years, based on their dates of birth) and randomly assigned (1:1) to the subunit and the split-virion ecNAIIV4 groups. All volunteers were intramuscularly administered a single vaccine dose at baseline, and children aged 3–8 years received a boosting dose at day 28. And the immune response was evaluated by measuring hemagglutinin-inhibition antibody titers against the four vaccine strains in blood samples. Safety profiles had nonsignificant differences between the study groups in ≥ 3 years cohort. Most adverse reactions post-vaccination, both local and systemic, were mild to moderate and resolved within 3 days. And no serious adverse events occurred. The immunogenicity of the trial vaccine was non-inferior to the comparator. Further, a two-dose vaccine series can provide better seroprotection than that of a one-dose series in children aged 3–8 years, with clinically acceptable safety profiles. Clinical Trials Registration. ChiCTR2100049934. [ABSTRACT FROM AUTHOR]

Without the implementation of mandatory vaccination, it was difficult to increase the influenza vaccination rate among healthcare workers. We described the strategy of personal coaching and assess its impact in increasing the influenza vaccination rate among healthcare workers in Hong Kong. Personal coaching of individual staff led by the infection control officer (ICO) and senior nursing officer (SNO) from infection control team could overcome barriers and promote on-site vaccination. The influenza vaccination rates among different categories of staff in 2016/2017 (year 1, baseline), 2017/2018 (year 2, promotion using social media), and 2018/2019 to 2020/2021 (year 3–5, promotion using personal coaching) were analysed in a healthcare region with 8490 ± 206 staff during the study period. With the implementation of personal coaching, the influenza vaccination rates increased significantly among medical (65.0% vs 57.0%, p = 0.048), nursing (30.6% vs 21.1%, p < 0.001), allied health (37.0% vs 27.4%, p < 0.001), care-related supporting staff (37.7% vs 27.3%, p < 0.001), and non-professional staff (27.3% vs 22.3%, p < 0.001) in year 3 compared with year 2, and also significantly increased among all staff in year 4 (38.0% vs 34.7%, p < 0.001) and year 5 (45.2% vs 38.0%, p < 0.001) when compared with the preceding year. The increase in vaccination rate was not apparent with social media promotion alone (26.4%, year 2 vs 25.6%, year 1, p = 0.305). Personal coaching led by ICO and SNO significantly increased the vaccination rates among healthcare workers in 3 consecutive years. This model could be promulgated to unit heads to establish a hospital culture conducive to vaccination. [ABSTRACT FROM AUTHOR]