A pan-influenza antibody inhibiting neuraminidase via receptor mimicry.

Rapidly evolving influenza A viruses (IAVs) and influenza B viruses (IBVs) are major causes of recurrent lower respiratory tract infections. Current influenza vaccines elicit antibodies predominantly to the highly variable head region of haemagglutinin and their effectiveness is limited by viral drift1 and suboptimal immune responses2. Here we describe a neuraminidase-targeting monoclonal antibody, FNI9, that potently inhibits the enzymatic activity of all group 1 and group 2 IAVs, as well as Victoria/2/87-like, Yamagata/16/88-like and ancestral IBVs. FNI9 broadly neutralizes seasonal IAVs and IBVs, including the immune-evading H3N2 strains bearing an N-glycan at position 245, and shows synergistic activity when combined with anti-haemagglutinin stem-directed antibodies. Structural analysis reveals that D107 in the FNI9 heavy chain complementarity-determinant region 3 mimics the interaction of the sialic acid carboxyl group with the three highly conserved arginine residues (R118, R292 and R371) of the neuraminidase catalytic site. FNI9 demonstrates potent prophylactic activity against lethal IAV and IBV infections in mice. The unprecedented breadth and potency of the FNI9 monoclonal antibody supports its development for the prevention of influenza illness by seasonal and pandemic viruses.

Recombinant or Standard-Dose Influenza Vaccine in Adults under 65 Years of Age.

BACKGROUND: Quadrivalent recombinant influenza vaccines contain three times the amount of hemagglutinin protein as standard-dose egg-based vaccines, and the recombinant formulation is not susceptible to antigenic drift during manufacturing. Data are needed on the relative effectiveness of recombinant vaccines as compared with standard-dose vaccines against influenza-related outcomes in adults under the age of 65 years. METHODS: In this cluster-randomized observational study, Kaiser Permanente Northern California facilities routinely administered either a high-dose recombinant influenza vaccine (Flublok Quadrivalent) or one of two standard-dose influenza vaccines during the 2018-2019 and 2019-2020 influenza seasons to adults 50 to 64 years of age (primary age group) and 18 to 49 years of age. Each facility alternated weekly between the two vaccine formulations. The primary outcome was influenza (A or B) confirmed by polymerase-chain-reaction (PCR) testing. Secondary outcomes included influenza A, influenza B, and influenza-related hospitalization outcomes. We used Cox regression analysis to estimate the hazard ratio of the recombinant vaccine as compared with the standard-dose vaccines against each outcome. We calculated the relative vaccine effectiveness as 1 minus the hazard ratio. RESULTS: The study population included 1,630,328 vaccinees between the ages of 18 and 64 years (632,962 in the recombinant-vaccine group and 997,366 in the standard-dose group). During this study period, 1386 cases of PCR-confirmed influenza were diagnosed in the recombinant-vaccine group and 2435 cases in the standard-dose group. Among the participants who were 50 to 64 years of age, 559 participants (2.00 cases per 1000) tested positive for influenza in the recombinant-vaccine group as compared with 925 participants (2.34 cases per 1000) in the standard-dose group (relative vaccine effectiveness, 15.3%; 95% confidence interval [CI], 5.9 to 23.8; P = 0.002). In the same age group, the relative vaccine effectiveness against influenza A was 15.7% (95% CI, 6.0 to 24.5; P = 0.002). The recombinant vaccine was not significantly more protective against influenza-related hospitalization than were the standard-dose vaccines. CONCLUSIONS: The high-dose recombinant vaccine conferred more protection against PCR-confirmed influenza than an egg-based standard-dose vaccine among adults between the ages of 50 and 64 years. (Funded by Sanofi; ClinicalTrials.gov number, NCT03694392.).

Multimodeling approach to evaluating the efficacy of layering pharmaceutical and nonpharmaceutical interventions for influenza pandemics.

When an influenza pandemic emerges, temporary school closures and antiviral treatment may slow virus spread, reduce the overall disease burden, and provide time for vaccine development, distribution, and administration while keeping a larger portion of the general population infection free. The impact of such measures will depend on the transmissibility and severity of the virus and the timing and extent of their implementation. To provide robust assessments of layered pandemic intervention strategies, the Centers for Disease Control and Prevention (CDC) funded a network of academic groups to build a framework for the development and comparison of multiple pandemic influenza models. Research teams from Columbia University, Imperial College London/Princeton University, Northeastern University, the University of Texas at Austin/Yale University, and the University of Virginia independently modeled three prescribed sets of pandemic influenza scenarios developed collaboratively by the CDC and network members. Results provided by the groups were aggregated into a mean-based ensemble. The ensemble and most component models agreed on the ranking of the most and least effective intervention strategies by impact but not on the magnitude of those impacts. In the scenarios evaluated, vaccination alone, due to the time needed for development, approval, and deployment, would not be expected to substantially reduce the numbers of illnesses, hospitalizations, and deaths that would occur. Only strategies that included early implementation of school closure were found to substantially mitigate early spread and allow time for vaccines to be developed and administered, especially under a highly transmissible pandemic scenario.

Antiviral Approaches against Influenza Virus.

Preventing and controlling influenza virus infection remains a global public health challenge, as it causes seasonal epidemics to unexpected pandemics. These infections are responsible for high morbidity, mortality, and substantial economic impact. Vaccines are the prophylaxis mainstay in the fight against influenza. However, vaccination fails to confer complete protection due to inadequate vaccination coverages, vaccine shortages, and mismatches with circulating strains. Antivirals represent an important prophylactic and therapeutic measure to reduce influenza-associated morbidity and mortality, particularly in high-risk populations. Here, we review current FDA-approved influenza antivirals with their mechanisms of action, and different viral- and host-directed influenza antiviral approaches, including immunomodulatory interventions in clinical development. Furthermore, we also illustrate the potential utility of machine learning in developing next-generation antivirals against influenza.

Costs and cost-effectiveness of influenza illness and vaccination in low- and middle-income countries: A systematic review from 2012 to 2022.

BACKGROUND: Historically, lack of data on cost-effectiveness of influenza vaccination has been identified as a barrier to vaccine use in low- and middle-income countries. We conducted a systematic review of economic evaluations describing (1) costs of influenza illness; (2) costs of influenza vaccination programs; and (3) vaccination cost-effectiveness from low- and middle-income countries to assess if gaps persist that could hinder global implementation of influenza vaccination programs. METHODS AND FINDINGS: We performed a systematic search in Medline, Embase, Cochrane Library, CINAHL, and Scopus in January 2022 and October 2023 using a combination of the following key words: "influenza" AND "cost" OR "economic." The search included studies with publication years 2012 through 2022. Studies were eligible if they (1) presented original, peer-reviewed findings on cost of illness, cost of vaccination program, or cost-effectiveness of vaccination for seasonal influenza; and (2) included data for at least 1 low- or middle-income country. We abstracted general study characteristics and data specific to each of the 3 study types. Of 54 included studies, 26 presented data on cost-effectiveness, 24 on cost-of-illness, and 5 on program costs. Represented countries were classified as upper-middle income (UMIC; n = 12), lower-middle income (LMIC; n = 7), and low-income (LIC; n = 3). The most evaluated target groups were children (n = 26 studies), older adults (n = 17), and persons with chronic medical conditions (n = 12); fewer studies evaluated pregnant persons (n = 9), healthcare workers (n = 5), and persons in congregate living settings (n = 1). Costs-of-illness were generally higher in UMICs than in LMICs/LICs; however, the highest national economic burden, as a percent of gross domestic product and national health expenditure, was reported from an LIC. Among studies that evaluated the cost-effectiveness of influenza vaccine introduction, most (88%) interpreted at least 1 scenario per target group as either cost-effective or cost-saving, based on thresholds designated in the study. Key limitations of this work included (1) heterogeneity across included studies; (2) restrictiveness of the inclusion criteria used; and (3) potential for missed influenza burden from use of sentinel surveillance systems. CONCLUSIONS: The 54 studies identified in this review suggest an increased momentum to generate economic evidence about influenza illness and vaccination from low- and middle-income countries during 2012 to 2022. However, given that we observed substantial heterogeneity, continued evaluation of the economic burden of influenza illness and costs/cost-effectiveness of influenza vaccination, particularly in LICs and among underrepresented target groups (e.g., healthcare workers and pregnant persons), is needed. Use of standardized methodology could facilitate pooling across settings and knowledge sharing to strengthen global influenza vaccination programs.

Influenza vaccination and use of lipid lowering therapies in adults with atherosclerotic cardiovascular disease: An analysis of the Behavioral Risk Factor Surveillance System (BRFSS).

BACKGROUND: Influenza vaccination and lipid lowering therapy (LLT) are evidence-based interventions with substantial benefit for individuals with established atherosclerotic cardiovascular disease (ASCVD). However, levels of influenza immunization and LLT use are low, possibly due to pervasive fear-based misinformation uniquely targeting vaccines and LLT. Whether being unvaccinated for influenza predicts lower utilization of LLT is unknown. OBJECTIVES: We tested the hypothesis that American adults with ASCVD who are unvaccinated for influenza have lower use of LLT even after accounting for traditional factors associated with underuse of preventive therapies. METHODS: We pooled 2017, 2019, and 2021 survey data from the Behavioral Risk Factor Surveillance System (BRFSS), and selected respondents aged 40 to 75 years with self-reported ASCVD. We used logistic regression models adjusted for potential confounders to examine the association between influenza vaccination and self-reported LLT use. We performed a sensitivity analysis with multiple imputation to account for missing data. All analyses accounted for complex survey weighting. RESULTS: Of 66,923 participants with ASCVD, 55% reported influenza vaccination in the last year and 76% reported using LLT. Being unvaccinated for influenza was associated with lower odds of LLT use (OR 0.54; 95% CI 0.50, 0.58; P< .001). In a multivariable regression model adjusting for demographics and comorbidities, this association remained statistically significant (aOR 0.58, 95% CI 0.52, 0.64, P < .001). After additional adjustment for preventive care engagement, health care access, and use patterns of other cardiovascular medications this association persisted (aOR 0.66; 95% CI 0.60, 0.74; P < .001). There were no significant differences across subgroups, including those with and without hyperlipidemia. CONCLUSIONS: Unvaccinated status for influenza was independently associated with 34% lower odds of LLT use among American adults with ASCVD after adjustment for traditional factors linked to underuse of preventive therapies. This finding identifies a population with excess modifiable ASCVD risk, and supports investigation into nontraditional mechanisms driving underuse of preventive therapies, including fear-based misinformation.

Evidence base for yearly respiratory virus vaccines: Current status and proposed improved strategies.

Annual vaccination is widely recommended for influenza and SARS-CoV-2. In this essay, we analyse and question the prevailing policymaking approach to these respiratory virus vaccines, especially in the United States. Every year, licensed influenza vaccines are reformulated to include specific strains expected to dominate in the season ahead. Updated vaccines are rapidly manufactured and approved without further regulatory requirement of clinical data. Novel vaccines (i.e. new products) typically undergo clinical trials, though generally powered for clinically unimportant outcomes (e.g. lab-confirmed infections, regardless of symptomatology or antibody levels). Eventually, the current and future efficacy of influenza and COVID-19 vaccines against hospitalization or death carries considerable uncertainty. The emergence of highly transmissible SARS-CoV-2 variants and waning vaccine-induced immunity led to plummeting vaccine effectiveness, at least against symptomatic infection, and booster doses have since been widely recommended. No further randomized trials were performed for clinically important outcomes for licensed updated boosters. In both cases, annual vaccine effectiveness estimates are generated by observational research, but observational studies are particularly susceptible to confounding and bias. Well-conducted experimental studies, particularly randomized trials, are necessary to address persistent uncertainties about influenza and COVID-19 vaccines. We propose a new research framework which would render results relevant to the current or future respiratory viral seasons. We demonstrate that experimental studies are feasible by adopting a more pragmatic approach and provide strategies on how to do so. When it comes to implementing policies that seriously impact people's lives, require substantial public resources and/or rely on widespread public acceptance, high evidence standards are desirable.

Real-World Coverage With Influenza, Pneumococcal, and Herpes Zoster Vaccines Among Patients With Rheumatic Diseases in a Nationwide Healthcare Plan.

OBJECTIVE: Vaccination against preventable infections is important for the management of rheumatic diseases (RDs). This study assessed the vaccination coverage and predictors among patients with RDs using real-world data from Israel. METHODS: This retrospective cross-sectional study, based on a Maccabi Healthcare Services database, included adult patients diagnosed with rheumatoid arthritis (RA), psoriatic arthritis (PsA), and systemic lupus erythematosus (SLE), as of April 30, 2019. Age-specific vaccination coverage for influenza (past year), pneumococcal (23-valent pneumococcal polysaccharide vaccine [PPSV23] and/or 13-valent pneumococcal conjugate vaccine [PCV13]), and live-attenuated herpes zoster (HZ) vaccines (past 5 years) was reported. Logistic regression was used to investigate predictors of vaccination. RESULTS: The study included 14,528 patients (RA: n = 6932; PsA: n = 4395; SLE: n = 1951; > 1 condition: n = 1250). Influenza vaccine coverage among patients with RA, PsA, and SLE was 45.1%, 36.2%, and 33.7%, respectively. For PPSV23, corresponding rates were 19.6%, 16.2%, and 12.6%, respectively. In the elderly population (≥ 65 years), 63.2% had influenza vaccine in the past year and 83.4% had a PPSV23 vaccine in the past 5 years or at age ≥ 65. For PCV13 and HZ, coverage in the overall study population was low at 4.8% and 3.6%, respectively. Central residence and treatment with corticosteroids and biologic or targeted synthetic disease-modifying antirheumatic drugs within the past 5 years were significant predictors of vaccination coverage across all vaccines (P < 0.05). Other predictors varied by vaccine, including female sex (influenza, PPSV23, PCV13), age (influenza, PPSV23), chronic comorbidities (influenza, PPSV23, PCV13), shorter disease duration (PCV13), and high socioeconomic status (PCV13, HZ). CONCLUSION: This study demonstrated suboptimal coverage of influenza, pneumococcal, and HZ vaccination in patients with RA, PsA, and SLE, in particular among younger adults in Israel.

County-Level Factors Associated With Influenza and COVID-19 Vaccination in Indiana, 2020‒2022.

Objectives. To assess COVID-19 and influenza vaccination rates across Indiana's 92 counties and identify county-level factors associated with vaccination. Methods. We analyzed county-level data on adult COVID-19 vaccination from the Indiana vaccine registry and 2021 adult influenza vaccination from the Centers for Disease Control and Prevention. We used multiple linear regression (MLR) to determine county-level predictors of vaccinations. Results. COVID-19 vaccination ranged from 31.2% to 87.6% (mean = 58.0%); influenza vaccination ranged from 33.7% to 53.1% (mean = 42.9%). In MLR, COVID-19 vaccination was significantly associated with primary care providers per capita (b = 0.04; 95% confidence interval [CI] = 0.02, 0.05), median household income (b = 0.23; 95% CI = 0.12, 0.34), percentage Medicare enrollees with a mammogram (b = 0.29; 95% CI = 0.08, 0.51), percentage uninsured (b = -1.22; 95% CI = -1.57, -0.87), percentage African American (b = 0.31; 95% CI = 0.19, 0.42), percentage female (b = -0.97; 95% CI = -1.79, ‒0.15), and percentage who smoke (b = -0.75; 95% CI = -1.26, -0.23). Influenza vaccination was significantly associated with percentage uninsured (b = 0.71; 95% CI = 0.22, 1.21), percentage African American (b = -0.07; 95% CI = -0.13, -0.01), percentage Hispanic (b = -0.28; 95% CI = -0.40, -0.17), percentage who smoke (b = -0.85; 95% CI = -1.06, -0.64), and percentage who completed high school (b = 0.54; 95% CI = 0.21, 0.87). The MLR models explained 86.7% (COVID-19) and 70.2% (influenza) of the variance. Conclusions. Factors associated with COVID-19 and influenza vaccinations varied. Variables reflecting access to care (e.g., insurance) and higher risk of severe disease (e.g., smoking) are notable. Programs to improve access and target high-risk populations may improve vaccination rates. (Am J Public Health. 2024;114(4):415-423. https://doi.org/10.2105/AJPH.2023.307553).

Effects of high-dose versus standard-dose quadrivalent influenza vaccine among patients with diabetes: A post-hoc analysis of the DANFLU-1 trial.

AIM: High-dose quadrivalent influenza vaccine (QIV-HD) has been shown to be more effective than standard-dose (QIV-SD) in reducing influenza infection, but whether diabetes status affects relative vaccine effectiveness (rVE) is unknown. We aimed to assess rVE on change in glycated haemoglobin [HbA1c (∆HbA1c)], incident diabetes, total all-cause hospitalizations (first + recurrent), and a composite of all-cause mortality and hospitalization for pneumonia or influenza. METHODS: DANFLU-1 was a pragmatic, open-label trial randomizing adults (65-79 years) 1:1 to QIV-HD or QIV-SD during the 2021/22 influenza season. Cox proportional hazards regression was used to estimate rVE against incident diabetes and the composite endpoint, negative binomial regression to estimate rVE against all-cause hospitalizations, and ANCOVA when assessing rVE against ∆HbA1c. RESULTS: Of the 12 477 participants, 1162 (9.3%) had diabetes at baseline. QIV-HD, compared with QIV-SD, was associated with a reduction in the rate of all-cause hospitalizations irrespective of diabetes [overall: 647 vs. 742 events, incidence rate ratio (IRR): 0.87, 95% CI (0.76-0.99); diabetes: 93 vs. 118 events, IRR: 0.80, 95% CI (0.55-1.15); without diabetes: 554 vs. 624 events, IRR: 0.88, 95% CI (0.76-1.01), pinteraction = 0.62]. Among those with diabetes, QIV-HD was associated with a lower risk of the composite outcome [2 vs. 11 events, HR: 0.18, 95% CI (0.04-0.83)] but had no effect on ∆HbA1c; QIV-HD adjusted mean difference: ∆ + 0.2 mmol/mol, 95% CI (-0.9 to 1.2). QIV-HD did not affect the risk of incident diabetes [HR 1.18, 95% CI (0.94-1.47)]. CONCLUSIONS: In this post-hoc analysis, QIV-HD versus QIV-SD was associated with an increased rVE against the composite of all-cause death and hospitalization for pneumonia/influenza, and the all-cause hospitalization rate irrespective of diabetes status.

Acceptability, cost-effectiveness, and capacity of a facility-based seasonal influenza vaccination among high-risk groups: a study protocol in selected tertiary care hospitals of Bangladesh.

BACKGROUND: In Bangladesh, seasonal influenza imposes considerable disease and economic burden, especially for those at high-risk of severe disease. The most successful approach for influenza prevention is the administration of a vaccine. Many poor and middle-income nations, including Bangladesh, do not have a national strategy or program in place for seasonal influenza vaccines, despite the World Health Organization's (WHO) advice to prioritize high-risk populations. Additionally, there is a scarcity of substantial data on the cost-effectiveness of seasonal influenza vaccination in these countries. The aim of our study is to determine acceptability, health beliefs, barriers, and intention of receiving influenza vaccine among high-risk populations, assess the cost-effectiveness of implementing a facility-based seasonal influenza vaccination programme, and investigate the required capacity for a potential seasonal influenza vaccination programme. METHODS: We will undertake this study following STROBE guidelines. We will conduct the study in inpatient and outpatient departments of three selected tertiary-level hospitals leveraging the ongoing hospital-based influenza surveillance (HBIS) platform. The study population will include the WHO-defined four high-risk groups excluding healthcare workers: children six months to eight years, pregnant women, elderly ≥ 60 years, and adults with chronic diseases. We will collect quantitative data on participants' acceptability, health beliefs, barriers, and vaccination intentions using the health belief model (HBM) from patients meeting the criteria for high-risk populations attending two public tertiary-level hospitals. In one of the two public tertiary-level hospitals, we will arrange an influenza vaccination campaign before the influenza season, where the vaccine will be offered free of cost to high-risk patients, and in the second hospital, vaccination will not be offered. Both the vaccinated and unvaccinated participants will then be followed-up once a month for one year to record any influenza-like illness, hospitalization, and death. Additional data for objective two will be collected from patients with symptoms of influenza-like illness (ILI) and severe acute respiratory infection (SARI) at one public and one private hospital to determine both direct and indirect costs associated with influenza illness. We will estimate the required number of influenza vaccines, safe injections, and total storage volume utilizing secondary data. We will use a deterministic Markov decision-analytic model to estimate the cost-effectiveness of facility-based influenza vaccination in Bangladesh. DISCUSSION: The results of this study will enable the National Immunization Technical Advisory Group and the Ministry of Health & Family Welfare of Bangladesh to decide what steps to take to develop and implement an influenza vaccination strategy targeting high-risk populations. TRIAL REGISTRATION: The Clinicaltrials.gov registration number is NCT05996549. The registration for the protocol version 2.0 took place in August 2023, with the initial participant being enrolled in March 2022.

Adequate immune responses to vaccines after chemotherapy for leukaemia diagnosed in childhood.

AIM: The survival rate after treatment for childhood leukaemia has greatly improved, but could result in protracted immune deficiency. This study examined the immune status of children after chemotherapy and evaluated their responses to immunisation. METHODS: Subjects who had completed their treatment for acute lymphoblastic leukaemia at The Children's Hospital Reykjavík, Iceland, during 2011-2020 had blood drawn and were then immunised for influenza in October 2021. Blood was drawn again 4 weeks later and their humoral and cellular responses were measured with a haemagglutination inhibition assay and lymphocyte stimulation test. Antibodies to other immunisations were also evaluated. RESULTS: We studied 18 patients (10 male) who had completed their treatment at 3.7-20.3 years of age (mean 9.1), 11-84 months (mean 36.9) before enrolment. Conventional immunological evaluation did not reveal notable abnormalities. The responses to several childhood vaccinations, including the pneumococcal conjugate vaccination, were adequate in most patients. Humoral responses to the influenza vaccine confirmed adequate reactions in all but one patient. Considerable variations were observed in the lymphocyte stimulations tests. CONCLUSION: Most patients reacted adequately to immunisation, especially against annual influenza and Streptococcus pneumoniae, reiterating the usefulness of vaccinations. The most appropriate timing for vaccination after treatment still needs to be determined.

Influenza in Pregnancy: Maternal, Obstetric, and Fetal Implications, Diagnosis, and Management.

Influenza(flu) in pregnancy is associated with higher rates of hospitalization, ICU admission, and death and with increased odds of congenital anomalies and stillbirth, but not preterm birth. Clinical manifestations of flu in pregnancy are the same as nonpregnant patients. Pregnant individuals with flu-like symptoms or flu exposure should be treated with antivirals. Diagnostic testing is not needed. Oseltamivir is the mainstay of treatment(and prophylaxis), and when given within 48 hours of symptom onset, it decreases morbidity and mortality. Influenza is associated with worse maternal, obstetric, and neonatal outcomes. These risks are mitigated by early oseltamivir treatment and maternal vaccination; hence the recommendation for universal vaccination in pregnancy.

Changes in Attitudes and Barriers to Seasonal Influenza Vaccination from 2007 to 2023.

This study investigated how factors and barriers to flu vaccination among college students has changed over the past 16 years. Data were collected from 440 students using a survey and compared to previous data from the same university. Respondents were also asked about their experiences with Covid-19 and its effect on their intent to vaccinate. We found that vaccination rates had increased from 12.4 to 30.5%. Among the unvaccinated, expense, fear of getting influenza from vaccination, fear of side effects, and lack of information have decreased by 28%, 20%, 17%, and 15% respectively. Time, convenience, and perceived risk are still significant barriers to vaccination. Students are getting more encouragement to vaccinate from their health care providers and parents, but it is becoming less effective. The Covid-19 pandemic has changed vaccine attitudes and vaccine fatigue has been a large contributor. Additionally, political affiliation has become a predictor of flu vaccine uptake with conservatives being less likely to vaccinate. There has also been a shift in motivation from concern for personal safety to concern for public safety.

Primary prevention of acute cardiovascular events by influenza vaccination: an observational study.

AIMS: Previous studies show a reduced incidence of first myocardial infarction and stroke 1-3 months after influenza vaccination, but it is unclear how underlying cardiovascular risk impacts the association. METHODS AND RESULTS: The study used linked Clinical Practice Research Datalink, Hospital Episode Statistics Admitted Patient Care and Office for National Statistics mortality data from England between 1 September 2008 and 31 August 2019. From the data, individuals aged 40-84 years with a first acute cardiovascular event and influenza vaccination occurring within 12 months of each September were selected. Using a self-controlled case series analysis, season-adjusted cardiovascular risk stratified incidence ratios (IRs) for cardiovascular events after vaccination compared with baseline time before and >120 days after vaccination were generated. 193 900 individuals with a first acute cardiovascular event and influenza vaccine were included. 105 539 had hypertension and 172 050 had a QRISK2 score ≥10%. In main analysis, acute cardiovascular event risk was reduced in the 15-28 days after vaccination [IR 0.72 (95% CI 0.70-0.74)] and, while the effect size tapered, remained reduced to 91-120 days after vaccination [0.83 (0.81-0.88)]. Reduced cardiovascular events were seen after vaccination among individuals of all age groups and with raised and low cardiovascular risk. CONCLUSIONS: Influenza vaccine may offer cardiovascular benefit among individuals at varying cardiovascular risk. Further studies are needed to characterize the populations who could derive the most cardiovascular benefits from vaccination.

Stroke Risk After COVID-19 Bivalent Vaccination Among US Older Adults.

Importance: In January 2023, the US Centers for Disease Control and Prevention and the US Food and Drug Administration noted a safety concern for ischemic stroke among adults aged 65 years or older who received the Pfizer-BioNTech BNT162b2; WT/OMI BA.4/BA.5 COVID-19 bivalent vaccine. Objective: To evaluate stroke risk after administration of (1) either brand of the COVID-19 bivalent vaccine, (2) either brand of the COVID-19 bivalent plus a high-dose or adjuvanted influenza vaccine on the same day (concomitant administration), and (3) a high-dose or adjuvanted influenza vaccine. Design, Setting, and Participants: Self-controlled case series including 11 001 Medicare beneficiaries aged 65 years or older who experienced stroke after receiving either brand of the COVID-19 bivalent vaccine (among 5 397 278 vaccinated individuals). The study period was August 31, 2022, through February 4, 2023. Exposures: Receipt of (1) either brand of the COVID-19 bivalent vaccine (primary) or (2) a high-dose or adjuvanted influenza vaccine (secondary). Main Outcomes and Measures: Stroke risk (nonhemorrhagic stroke, transient ischemic attack, combined outcome of nonhemorrhagic stroke or transient ischemic attack, or hemorrhagic stroke) during the 1- to 21-day or 22- to 42-day risk window after vaccination vs the 43- to 90-day control window. Results: There were 5 397 278 Medicare beneficiaries who received either brand of the COVID-19 bivalent vaccine (median age, 74 years [IQR, 70-80 years]; 56% were women). Among the 11 001 beneficiaries who experienced stroke after receiving either brand of the COVID-19 bivalent vaccine, there were no statistically significant associations between either brand of the COVID-19 bivalent vaccine and the outcomes of nonhemorrhagic stroke, transient ischemic attack, nonhemorrhagic stroke or transient ischemic attack, or hemorrhagic stroke during the 1- to 21-day or 22- to 42-day risk window vs the 43- to 90-day control window (incidence rate ratio [IRR] range, 0.72-1.12). Among the 4596 beneficiaries who experienced stroke after concomitant administration of either brand of the COVID-19 bivalent vaccine plus a high-dose or adjuvanted influenza vaccine, there was a statistically significant association between vaccination and nonhemorrhagic stroke during the 22- to 42-day risk window for the Pfizer-BioNTech BNT162b2; WT/OMI BA.4/BA.5 COVID-19 bivalent vaccine (IRR, 1.20 [95% CI, 1.01-1.42]; risk difference/100 000 doses, 3.13 [95% CI, 0.05-6.22]) and a statistically significant association between vaccination and transient ischemic attack during the 1- to 21-day risk window for the Moderna mRNA-1273.222 COVID-19 bivalent vaccine (IRR, 1.35 [95% CI, 1.06-1.74]; risk difference/100 000 doses, 3.33 [95% CI, 0.46-6.20]). Among the 21 345 beneficiaries who experienced stroke after administration of a high-dose or adjuvanted influenza vaccine, there was a statistically significant association between vaccination and nonhemorrhagic stroke during the 22- to 42-day risk window (IRR, 1.09 [95% CI, 1.02-1.17]; risk difference/100 000 doses, 1.65 [95% CI, 0.43-2.87]). Conclusions and Relevance: Among Medicare beneficiaries aged 65 years or older who experienced stroke after receiving either brand of the COVID-19 bivalent vaccine, there was no evidence of a significantly elevated risk for stroke during the days immediately after vaccination.

Evaluating socioeconomic inequalities in influenza vaccine uptake during the COVID-19 pandemic: A cohort study in Greater Manchester, England.

BACKGROUND: There are known socioeconomic inequalities in annual seasonal influenza (flu) vaccine uptake. The Coronavirus Disease 2019 (COVID-19) pandemic was associated with multiple factors that may have affected flu vaccine uptake, including widespread disruption to healthcare services, changes to flu vaccination eligibility and delivery, and increased public awareness and debate about vaccination due to high-profile COVID-19 vaccination campaigns. However, to the best of our knowledge, no existing studies have investigated the consequences for inequalities in flu vaccine uptake, so we aimed to investigate whether socioeconomic inequalities in flu vaccine uptake have widened since the onset of the COVID-19 pandemic. METHODS AND FINDINGS: We used deidentified data from electronic health records for a large city region (Greater Manchester, population 2.8 million), focusing on 3 age groups eligible for National Health Service (NHS) flu vaccination: preschool children (age 2 to 3 years), primary school children (age 4 to 9 years), and older adults (age 65 years plus). The sample population varied between 418,790 (2015/16) and 758,483 (2021/22) across each vaccination season. We estimated age-adjusted neighbourhood-level income deprivation-related inequalities in flu vaccine uptake using Cox proportional hazards models and the slope index of inequality (SII), comparing 7 flu vaccination seasons (2015/16 to 2021/22). Among older adults, the SII (i.e., the gap in uptake between the least and most income-deprived areas) doubled over the 7 seasons from 8.48 (95% CI [7.91,9.04]) percentage points to 16.91 (95% CI [16.46,17.36]) percentage points, with approximately 80% of this increase occurring during the pandemic. Before the pandemic, income-related uptake gaps were wider among children, ranging from 15.59 (95% CI [14.52,16.67]) percentage points to 20.07 (95% CI [18.94,21.20]) percentage points across age groups and vaccination seasons. Among preschool children, the uptake gap increased in 2020/21 to 25.25 (95% CI [24.04,26.45]) percentage points, before decreasing to 20.86 (95% CI [19.65,22.05]) percentage points in 2021/22. Among primary school children, inequalities increased in both pandemic years to reach 30.27 (95% CI [29.58,30.95]) percentage points in 2021/22. Although vaccine uptake increased during the pandemic, disproportionately larger increases in uptake in less deprived areas created wider inequalities in all age groups. The main limitation of our approach is the use of a local dataset, which may limit generalisability to other geographical settings. CONCLUSIONS: The COVID-19 pandemic led to increased inequalities in flu vaccine uptake, likely due to changes in demand for vaccination, new delivery models, and disruptions to healthcare and schooling. It will be important to investigate the causes of these increased inequalities and to examine whether these increased inequalities also occurred in the uptake of other routine vaccinations. These new wider inequalities in flu vaccine uptake may exacerbate inequalities in flu-related morbidity and mortality.

Genetic and biological properties of H7N9 avian influenza viruses detected after application of the H7N9 poultry vaccine in China.

The H7N9 avian influenza virus (AIV) that emerged in China have caused five waves of human infection. Further human cases have been successfully prevented since September 2017 through the use of an H7N9 vaccine in poultry. However, the H7N9 AIV has not been eradicated from poultry in China, and its evolution remains largely unexplored. In this study, we isolated 19 H7N9 AIVs during surveillance and diagnosis from February 2018 to December 2019, and genetic analysis showed that these viruses have formed two different genotypes. Animal studies indicated that the H7N9 viruses are highly lethal to chicken, cause mild infection in ducks, but have distinct pathotypes in mice. The viruses bound to avian-type receptors with high affinity, but gradually lost their ability to bind to human-type receptors. Importantly, we found that H7N9 AIVs isolated in 2019 were antigenically different from the H7N9 vaccine strain that was used for H7N9 influenza control in poultry, and that replication of these viruses cannot, therefore, be completely prevented in vaccinated chickens. We further revealed that two amino acid mutations at positions 135 and 160 in the HA protein added two glycosylation sites and facilitated the escape of the H7N9 viruses from the vaccine-induced immunity. Our study provides important insights into H7N9 virus evolution and control.

Vaccine Attitudes and COVID-19 Vaccine Intention Among Parents of Children With Kidney Disease or Primary Hypertension.

RATIONALE & OBJECTIVE: Children with kidney disease and primary hypertension may be more vulnerable to COVID-19. We examined COVID-19 vaccine hesitancy among parents of children with chronic kidney disease or hypertension. STUDY DESIGN: Sequential explanatory mixed-methods design; survey followed by in-depth interviews. SETTING & PARTICIPANTS: Parents of children aged <18 years with kidney disease or primary hypertension within a large pediatric practice. EXPOSURE: Parental attitudes toward general childhood and influenza vaccines assessed by the Vaccine Hesitancy Scale. Kidney disease classification, demographic and socioeconomic factors, experiences with COVID-19, COVID-19 mitigation activities and self-efficacy, and sources of vaccine information. OUTCOME: Willingness to vaccinate child against COVID-19. ANALYTICAL APPROACH: Analysis of variance (ANOVA) test to compare parental attitudes toward general childhood and influenza vaccination with attitudes toward COVID-19 vaccination. Multinomial logistic regression to assess predictors of willingness to vaccinate against COVID-19. Thematic analysis of interview data to characterize influences on parental attitudes. RESULTS: Of the participants, 207 parents completed the survey (39% of approached): 75 (36%) were willing, 80 (39%) unsure, and 52 (25%) unwilling to vaccinate their child against COVID-19. Hesitancy toward general childhood and influenza vaccines was highest among the unwilling group (P < 0.001). More highly educated parents more likely to be willing to vaccinate their children, while Black race was associated with being more likely to be unwilling. Rushed COVID-19 vaccine development as well as fear of serious and unknown long-term side effects were themes that differed across the parental groups that were willing, unsure, or unwilling to vaccinate their children. Although doctors and health care teams are trusted sources of vaccine information, perceptions of benefit versus harm and experiences with doctors differed among these 3 groups. The need for additional information on COVID-19 vaccines was greatest among those unwilling or unsure about vaccinating. LIMITATIONS: Generalizability may be limited. CONCLUSIONS: Two-thirds of parents of children with kidney disease or hypertension were unsure or unwilling to vaccinate their child against COVID-19. Higher hesitancy toward routine childhood and influenza vaccination was associated with hesitancy toward COVID-19 vaccines. Enhanced communication of vaccine information relevant to kidney patients in an accessible manner should be examined as a means to reduce vaccine hesitancy. PLAIN-LANGUAGE SUMMARY: Children with kidney disease or hypertension may do worse with COVID-19. As there are now effective vaccines to protect children from COVID-19, we wanted to find out what parents think about COVID-19 vaccines and what influences their attitudes. We surveyed and then interviewed parents of children who had received a kidney transplant, were receiving maintenance dialysis, had chronic kidney disease, or had hypertension. We found that two-thirds of parents were hesitant to vaccinate their children. Their reasons varied, but the key issues included the need for information pertinent to their child and a consistent message from doctors and other health care providers. These findings may inform an effective vaccine campaign to protect children with kidney disease and hypertension.

Prevention and Control of Seasonal Influenza with Vaccines: Recommendations of the Advisory Committee on Immunization Practices - United States, 2022-23 Influenza Season.

THIS REPORT UPDATES THE 2021-22 RECOMMENDATIONS OF THE ADVISORY COMMITTEE ON IMMUNIZATION PRACTICES (ACIP) CONCERNING THE USE OF SEASONAL INFLUENZA VACCINES IN THE UNITED STATES: (MMWR Recomm Rep 2021;70[No. RR-5]:1-24). Routine annual influenza vaccination is recommended for all persons aged ≥6 months who do not have contraindications. For each recipient, a licensed and age-appropriate vaccine should be used. With the exception of vaccination for adults aged ≥65 years, ACIP makes no preferential recommendation for a specific vaccine when more than one licensed, recommended, and age-appropriate vaccine is available. All seasonal influenza vaccines expected to be available in the United States for the 2022-23 season are quadrivalent, containing hemagglutinin (HA) derived from one influenza A(H1N1)pdm09 virus, one influenza A(H3N2) virus, one influenza B/Victoria lineage virus, and one influenza B/Yamagata lineage virus. Inactivated influenza vaccines (IIV4s), recombinant influenza vaccine (RIV4), and live attenuated influenza vaccine (LAIV4) are expected to be available. Trivalent influenza vaccines are no longer available, but data that involve these vaccines are included for reference. INFLUENZA VACCINES MIGHT BE AVAILABLE AS EARLY AS JULY OR AUGUST, BUT FOR MOST PERSONS WHO NEED ONLY 1 DOSE OF INFLUENZA VACCINE FOR THE SEASON, VACCINATION SHOULD IDEALLY BE OFFERED DURING SEPTEMBER OR OCTOBER. HOWEVER, VACCINATION SHOULD CONTINUE AFTER OCTOBER AND THROUGHOUT THE SEASON AS LONG AS INFLUENZA VIRUSES ARE CIRCULATING AND UNEXPIRED VACCINE IS AVAILABLE. FOR MOST ADULTS (PARTICULARLY ADULTS AGED ≥65 YEARS) AND FOR PREGNANT PERSONS IN THE FIRST OR SECOND TRIMESTER, VACCINATION DURING JULY AND AUGUST SHOULD BE AVOIDED UNLESS THERE IS CONCERN THAT VACCINATION LATER IN THE SEASON MIGHT NOT BE POSSIBLE. CERTAIN CHILDREN AGED 6 MONTHS THROUGH 8 YEARS NEED 2 DOSES; THESE CHILDREN SHOULD RECEIVE THE FIRST DOSE AS SOON AS POSSIBLE AFTER VACCINE IS AVAILABLE, INCLUDING DURING JULY AND AUGUST. VACCINATION DURING JULY AND AUGUST CAN BE CONSIDERED FOR CHILDREN OF ANY AGE WHO NEED ONLY 1 DOSE FOR THE SEASON AND FOR PREGNANT PERSONS WHO ARE IN THE THIRD TRIMESTER IF VACCINE IS AVAILABLE DURING THOSE MONTHS: UPDATES DESCRIBED IN THIS REPORT REFLECT DISCUSSIONS DURING PUBLIC MEETINGS OF ACIP THAT WERE HELD ON OCTOBER 20, 2021; JANUARY 12, 2022; FEBRUARY 23, 2022; AND JUNE 22, 2022. PRIMARY UPDATES TO THIS REPORT INCLUDE THE FOLLOWING THREE TOPICS: 1) THE COMPOSITION OF 2022-23 U.S. SEASONAL INFLUENZA VACCINES; 2) UPDATES TO THE DESCRIPTION OF INFLUENZA VACCINES EXPECTED TO BE AVAILABLE FOR THE 2022-23 SEASON, INCLUDING ONE INFLUENZA VACCINE LABELING CHANGE THAT OCCURRED AFTER THE PUBLICATION OF THE 2021-22 ACIP INFLUENZA RECOMMENDATIONS; AND 3) UPDATES TO THE RECOMMENDATIONS CONCERNING VACCINATION OF ADULTS AGED ≥65 YEARS. FIRST, THE COMPOSITION OF 2022-23 U.S. INFLUENZA VACCINES INCLUDES UPDATES TO THE INFLUENZA A(H3N2) AND INFLUENZA B/VICTORIA LINEAGE COMPONENTS. U.S.-LICENSED INFLUENZA VACCINES WILL CONTAIN HA DERIVED FROM AN INFLUENZA A/VICTORIA/2570/2019 (H1N1)PDM09-LIKE VIRUS (FOR EGG-BASED VACCINES) OR AN INFLUENZA A/WISCONSIN/588/2019 (H1N1)PDM09-LIKE VIRUS (FOR CELL CULTURE-BASED OR RECOMBINANT VACCINES); AN INFLUENZA A/DARWIN/9/2021 (H3N2)-LIKE VIRUS (FOR EGG-BASED VACCINES) OR AN INFLUENZA A/DARWIN/6/2021 (H3N2)-LIKE VIRUS (FOR CELL CULTURE-BASED OR RECOMBINANT VACCINES); AN INFLUENZA B/AUSTRIA/1359417/2021 (VICTORIA LINEAGE)-LIKE VIRUS; AND AN INFLUENZA B/PHUKET/3073/2013 (YAMAGATA LINEAGE)-LIKE VIRUS. SECOND, THE APPROVED AGE INDICATION FOR THE CELL CULTURE-BASED INACTIVATED INFLUENZA VACCINE, FLUCELVAX QUADRIVALENT (CCIIV4), WAS CHANGED IN OCTOBER 2021 FROM ≥2 YEARS TO ≥6 MONTHS. THIRD, RECOMMENDATIONS FOR VACCINATION OF ADULTS AGED ≥65 YEARS HAVE BEEN MODIFIED. ACIP RECOMMENDS THAT ADULTS AGED ≥65 YEARS PREFERENTIALLY RECEIVE ANY ONE OF THE FOLLOWING HIGHER DOSE OR ADJUVANTED INFLUENZA VACCINES: QUADRIVALENT HIGH-DOSE INACTIVATED INFLUENZA VACCINE (HD-IIV4), QUADRIVALENT RECOMBINANT INFLUENZA VACCINE (RIV4), OR QUADRIVALENT ADJUVANTED INACTIVATED INFLUENZA VACCINE (AIIV4). IF NONE OF THESE THREE VACCINES IS AVAILABLE AT AN OPPORTUNITY FOR VACCINE ADMINISTRATION, THEN ANY OTHER AGE-APPROPRIATE INFLUENZA VACCINE SHOULD BE USED: THIS REPORT FOCUSES ON RECOMMENDATIONS FOR THE USE OF VACCINES FOR THE PREVENTION AND CONTROL OF SEASONAL INFLUENZA DURING THE 2022-23 INFLUENZA SEASON IN THE UNITED STATES. A BRIEF SUMMARY OF THE RECOMMENDATIONS AND A LINK TO THE MOST RECENT BACKGROUND DOCUMENT CONTAINING ADDITIONAL INFORMATION ARE AVAILABLE AT: https://www.cdc.gov/vaccines/hcp/acip-recs/vacc-specific/flu.html. These recommendations apply to U.S.-licensed influenza vaccines used according to Food and Drug Administration-licensed indications. Updates and other information are available from CDC's influenza website (https://www.cdc.gov/flu). Vaccination and health care providers should check this site periodically for additional information.