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Seasonal influenza epidemics result in high levels of healthcare utilization. Vaccination is an effective strategy to reduce the influenza-related burden of disease. However, reporting vaccine effectiveness does not convey the population impacts of influenza vaccination. We aimed to calculate the burden of influenza-related hospitalizations and emergency department (ED) attendance averted by influenza vaccination in Victoria, Australia, from 2017 to 2019, and associated economic savings. We applied a compartmental model to hospitalizations and ED attendances with influenza-specific, and pneumonia and influenza (P&I) with the International Classification of Diseases, 10th Revision, Australian Modification (ICD-10-AM) diagnostic codes of J09-J11 and J09-J18, respectively. We estimated an annual average of 7657 (120 per 100000 population) hospitalizations and 20560 (322 per 100000 population) ED attendances over the study period, associated with A$85 million hospital expenditure. We estimated that influenza vaccination averted an annual average of 1182 [range: 556 - 2277] hospitalizations and 3286 [range: 1554 - 6257] ED attendances and reduced the demand for healthcare services at the influenza season peak. This equated to approximately A13 [range: A6 - A25] million of savings over the study period. Calculating the burden averted is feasible in Australia and auseful approach to demonstrate the health and economic benefits of influenza vaccination.

BACKGROUND: This report summarizes the discussions and conclusions from the Correlates of Protection for Next Generation Influenza Vaccines: Lessons Learned from the COVID-19 Pandemic meeting, which took place in Seattle, USA, from March 1, 2023, to March 3, 2023. CONCLUSIONS: Discussions around influenza virus correlates of protection and their use continued from where the discussion had been left off in 2019. While there was not much progress in the influenza field itself, many lessons learned during the coronavirus disease 2019 (COVID-19) pandemic, especially the importance of mucosal immunity, were discussed and can directly be applied to influenza correlates of protection.

BACKGROUND: The effect of vaccination on the epigenome remains poorly characterized. In previous research, we identified an association between seroprotection against influenza and DNA methylation at sites associated with the RIG-1 signaling pathway, which recognizes viral double-stranded RNA and leads to a type I interferon response. However, these studies did not fully account for confounding factors including age, gender, and BMI, along with changes in cell-type composition. RESULTS: Here, we studied the influenza vaccine response in a longitudinal cohort vaccinated over two consecutive years (2019-2020 and 2020-2021), using peripheral blood mononuclear cells and a targeted DNA methylation approach. To address the effects of multiple factors on the epigenome, we designed a multivariate multiple regression model that included seroprotection levels as quantified by the hemagglutination-inhibition (HAI) assay test. CONCLUSIONS: Our findings indicate that 179 methylation sites can be combined as potential signatures to predict seroprotection. These sites were not only enriched for genes involved in the regulation of the RIG-I signaling pathway, as found previously, but also enriched for other genes associated with innate immunity to viruses and the transcription factor binding sites of BRD4, which is known to impact T cell memory. We propose a model to suggest that the RIG-I pathway and BRD4 could potentially be modulated to improve immunization strategies.

Current antigen delivery platforms, such as alum and nanoparticles, are not readily tunable, thus may not generate optimal adaptive immune responses. We created an antigen delivery platform by loading lyophilized Microporous Annealed Particle (MAP) with aqueous solution containing target antigens. Upon administration of antigen loaded MAP (VaxMAP), the biomaterial reconstitution forms an instant antigen-loaded porous scaffold area with a sustained release profile to maximize humoral immunity. VaxMAP induced CD4+ T follicular helper (Tfh) cells and germinal center (GC) B cell responses in the lymph nodes similar to Alum. VaxMAP loaded with SARS-CoV-2 spike protein improved the magnitude, neutralization, and duration of anti-receptor binding domain antibodies compared to Alum vaccinated mice. A single injection of Influenza specific HA1-loaded-VaxMAP enhanced neutralizing antibodies and elicited greater protection against influenza virus challenge than HA1-loaded-Alum. Thus, VaxMAP is a platform that can be used to promote adaptive immune cell responses to generate more robust neutralizing antibodies, and better protection upon pathogen challenge.

The aim of this project was to increase willingness to receive the influenza vaccine to the optimal rate of ≥ 70%. Low acuity adult patients who visited an Emergency Department (ED) were assessed regarding their willingness to receive the influenza vaccine before and after an educational intervention that included a provider recommendation and an educational handout. A total of seventy-six patients (n = 76) were assessed. Patients willingness to receive the influenza vaccine rose from 29% pre-intervention to 72% post-intervention without disrupting the clinical flow in a busy ED. Similar vaccine educational strategies can be applied to influenza and other vaccines in EDs  to increase vaccination willingness in patients, including those who use the ED as a primary point of contact for healthcare, decreasing the burden of influenza illness in the community.

SARS-CoV-2 and influenza have caused substantial health threats. SARS-CoV-2 had caused >0.7 billion reported cases and 6.9 million deaths globally by May 2023, when the World Health Organization (WHO) declared [...]

ImportanceIncreasing influenza vaccination rates is a public health priority. One method recommended by the US Centers for Disease Control and Prevention and others is for health systems to send reminders nudging patients to be vaccinated.ObjectiveTo evaluate and compare the effect of electronic health record (EHR)-based patient portal reminders vs text message reminders on influenza vaccination rates across a health system.Design, setting, and participantsThis 3-arm randomized clinical trial was conducted from September 7, 2022, to April 30, 2023, among primary care patients within the University of California, Los Angeles (UCLA) health system.InterventionsArm 1 received standard of care. The health system sent monthly reminder messages to patients due for an influenza vaccine by portal (arm 2) or text (arm 3). Arm 2 had a 2 × 2 nested design, with fixed vs responsive monthly reminders and preappointment vs no preappointment reminders. Arm 3 had 1 × 2 design, with preappointment vs no preappointment reminders. Preappointment reminders for eligible patients were sent 24 and 48 hours before scheduled primary care visits. Fixed reminders (in October, November, and December) involved identical messages via portal or text. Responsive portal reminders involved a September message asking patients about their plans for vaccination, with a follow-up reminder if the response was affirmative but the patient was not yet vaccinated.Main outcomes and measuresThe primary outcome was influenza vaccination by April 30, 2023, obtained from the UCLA EHR, including vaccination from pharmacies and other sources.ResultsA total of 262 085 patients (mean [SD] age, 45.1 [20.7] years; 237 404 [90.6%] adults; 24 681 [9.4%] children; 149 349 [57.0%] women) in 79 primary care practices were included (87 257 in arm 1, 87 478 in arm 2, and 87 350 in arm 3). At the entire primary care population level, none of the interventions improved influenza vaccination rates. All groups had rates of approximately 47%. There was no statistical or clinically significant improvement following portal vs text, preappointment reminders vs no preappointment reminders (portal and text reminders combined), or responsive vs fixed monthly portal reminders.Conclusions and relevanceAt the population level, neither portal nor text reminders for influenza vaccination were effective. Given that vaccine hesitancy may be a major reason for the lack of impact of portal or text reminders, more intensive interventions by health systems are needed to raise influenza vaccination coverage levels.Trial registrationClinicalTrials.gov Identifier: NCT05525494.

Global control of infectious diseases depends on the continuous development and deployment of diverse vaccination strategies. Currently available live-attenuated and killed virus vaccines typically take a week or longer to activate specific protection by the adaptive immunity. The mosquito-transmitted Nodamura virus (NoV) is attenuated in mice by mutations that prevent expression of the B2 viral suppressor of RNA interference (VSR) and consequently, drastically enhance in vivo production of the virus-targeting small-interfering RNAs. We reported recently that 2 d after immunization with live-attenuated VSR-disabled NoV (NoVΔB2), neonatal mice become fully protected against lethal NoV challenge and develop no detectable infection. Using Rag1-/- mice that produce no mature B and T lymphocytes as a model, here we examined the hypothesis that adaptive immunity is dispensable for the RNAi-based protective immunity activated by NoVΔB2 immunization. We show that immunization of both neonatal and adult Rag1-/- mice with live but not killed NoVΔB2 induces full protection against NoV challenge at 2 or 14 d postimmunization. Moreover, NoVΔB2-induced protective antiviral immunity is virus-specific and remains effective in adult Rag1-/- mice 42 and 90 d after a single-shot immunization. We conclude that immunization with the live-attenuated VSR-disabled RNA virus vaccine activates rapid and long-lasting protective immunity against lethal challenges by a distinct mechanism independent of the adaptive immunity mediated by B and T cells. Future studies are warranted to determine whether additional animal and human viruses attenuated by VSR inactivation induce similar protective immunity in healthy and adaptive immunity-compromised individuals.

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

Background: Influenza A viruses (IAVs) cause seasonal influenza epidemics and pose significant threats to public health. However, seasonal influenza vaccines often elicit strain-specific immune responses and confer little protection against mismatched strains. There is an urgent need to develop universal influenza vaccines against emerging and potentially re-emerging influenza virus infections. Multiepitope vaccines combining multiple conserved epitopes can induce more robust and broader immune responses and provide a potential solution. Results: Here, we demonstrated that an HA chimeric multiepitope nanoparticle vaccine, delivered intranasally conferred broad protection against challenges with various influenza viruses in mice. The nanoparticle vaccine co-expresses the ectodomain of haemagglutinin (H), three repeated highly conserved ectodomains of matrix protein 2 (M), and the M-cell-targeting ligand Co4B (C) in a baculovirus-insect cell system. These elements (C, H and M) were presented on the surface of self-assembling ferritin (f) in tandem to generate a nanoparticle denoted as CHM-f. Intranasal vaccination with CHM-f nanoparticles elicited robust humoral and cellular immune responses, conferring complete protection against a variety of IAVs, including the A/PR8/34 H1N1 strain, the swine flu H3N2 strain, the avian flu H5N8 strain, and H9N2. When CHM-f nanoparticles adjuvanted with CpG IAMA-002, the weight loss protective effect, cellular immune responses and mucosal IgA responses were significantly augmented. Compared with controls, mice immunized with CHM-f nanoparticles with or without CpG IAMA-002 showed significant reductions in weight loss, lung viral titres and pathological changes. Conclusions: These results suggest that CHM-f nanoparticle with or without CpG IAMA-002 is a promising candidate as a universal influenza vaccine. [ABSTRACT FROM AUTHOR]

Background: While influenza vaccines are the most effective measure for preventing influenza, uptake rates in China remain relatively low. Rapid Verbal Persuasion (RVP), with highly rapid fashion, has a strong evidence base in promoting behavior change. Despite this, it is underused or rarely evaluated in the context of vaccination. Additionally, the success of RVP implementation in vaccination clinics hinges on the motivation of vaccination staff, which remains critical even with stable contextual factors. Multifaceted incentive-based implementation strategies, which aim to enhance motivation to promote the implementation of evidence-based practices, could be advantageous. This study protocol outlines an implementation-effectiveness hybrid type 2 design to evaluate the effectiveness of both the incentive-based implementation strategies on implementation outcomes and RVP on increasing influenza vaccination rates. Method: This study will be conducted as a two-tiered cluster of randomized controlled trials over three months. Initially, 32 vaccination clinics will be randomly allocated to one of two study arms: (a) implementation of RVP or (b) no implementation. At the end of the study period, differences in influenza vaccination status between the intervention and control groups will be compared (primary outcome). Subsequently, a cluster randomized factorial trial will be conducted, involving 16 clinics implementing RVP. This trial will aim to compare the impact of various implementation strategies (different combinations of incentives) on fidelity in RVP implementation (primary outcome). Data collection for the primary outcomes will include unannounced exit interviews. Modified Poisson regression models and generalized linear mixed-effects models will be utilized to analyze the association between primary outcomes and interventions. Conclusion: The study aims to enhance the influenza vaccination rate in China by developing financial and non-financial incentives that allow vaccination staff to deliver RVP with greater motivation. Furthermore, the evidence generated from this multi-center trial will assist policymakers in improving current incentive systems within immunization services. Trial registration: Chinese Clinical Trial Registry. Trial identifier: ChiCTR2400091302 (Registration Date: October 25, 2024); ChiCTR2400091324 (Registration Date: October 25, 2024). [ABSTRACT FROM AUTHOR]

Background: Influenza is a seasonal infection with a huge impact on morbidity and mortality in older adults, for whom vaccination is recommended. New influenza vaccines for this population have been introduced in Spain in the past 5 years, and a number of cost-effectiveness analyses (CEA) have been published to aid healthcare decision-making. The objective of this study was to assess possible sources of uncertainty in the CEAs of influenza vaccines for the older adults in Spain. Methods: A systematic review was performed to identify Spanish CEAs published since 2016. Potential sources of structural, methodologic and parametric uncertainty in CEA results were systematically analysed using the TRansparent Uncertainty ASsessmenT (TRUST) Tool, quality assessment checklists, and the WHO guidance on economic evaluations of influenza vaccine strategies. The primary sources of efficacy/effectiveness were analysed in depth to ascertain whether they could support the conclusions of the respective CEAs. Results: Seven CEAs were included. Overall, they were designed and performed in accordance with the applicable guidelines; however, some critical sources of uncertainty were detected, mainly: (1) the choice and use of efficacy/effectiveness data (real-world single season studies, meta-analyses including studies with high risk of bias and/or high heterogeneity with biased interpretation); (2) use of fewer than 5 seasons to estimate influenza burden; (3) generalized use of influenza-like illness data to estimate effectiveness and burden, among others. Conclusions: Seemingly well-designed studies may conceal important sources of uncertainty that affect the results. This must be taken into account when interpreting results to support decision-making. [ABSTRACT FROM AUTHOR]

A BioSafe-sponsored survey investigated how vaccine companies (n = 12) perceive the value of the repeat-dose toxicity studies for safety assessment of vaccine candidates. As all major vaccine developers were part of the survey, it was considered representative for the industry practices up to 2022. Vaccine developers indicated that they see scientific value in performing repeat-dose toxicity studies with vaccines, especially when novel components (e.g., adjuvant) or technology is being used. However, a few (3/12) also indicated that repeat-dose toxicity studies could be replaced by a pharmacology study with additional toxicity parameters. For the majority of companies (9/12), findings from the repeat-dose toxicity studies never prevented or postponed a first-in-human (FIH) trial. In the remaining 3 companies, a total of 4 occurrences of postponement or prevention of clinical development occurred and in only 2 of these cases was the finding considered related to the vaccine. A platform approach has been successfully implemented for influenza vaccines already in 2016, and an outline of the regulatory requirements for a platform approach has been recently documented in the latest infectious disease mRNA-LNP vaccine guideline, as well as in the guidance on the development and licensure of COVID-19 vaccines presented by the FDA. Vaccine developers are seeking to extend this platform approach to the development of new vaccines, building on established technologies and using well-defined manufacturing processes. This approach could support reduction of animal use (a principle of 3Rs) while still providing reassurance of the nonclinical safety of these products. [ABSTRACT FROM AUTHOR]

Objectives. To estimate the effect of influenza vaccination disparities. Methods. We compared symptomatic influenza cases between Black and White races in 2 scenarios: (1) race- and age-specific vaccination coverage and (2) equal vaccination coverage. We also compared differences in household composition between races. We used the Framework for Reconstructing Epidemiological Dynamics, an agent-based model that assigns US Census‒based age, race, households, and geographic location to agents (individual people), in US counties of varying racial and age composition. Results. Influenza cases were highest in counties with higher proportions of children. Cases were up to 30% higher in Black agents with both race-based and race-equal vaccination coverage. Compared with corresponding categories of White households, cases in Black households without children were lower and with children were higher. Conclusions. Racial disparities in influenza cases persisted after equalizing vaccination coverage. The proportion of children in the population contributed to the number of influenza cases regardless of race. Differences in household composition may provide insight into racial differences and offer an opportunity to improve vaccination coverage to reduce influenza burden for both races. (Am J Public Health. 2025;115(2):209–216. https://doi.org/10.2105/AJPH.2024.307878) [ABSTRACT FROM AUTHOR]

To battle seasonal outbreaks of influenza B virus infection, which continue to pose a major threat to world health, new and improved vaccines are urgently needed. In this article, we discuss the current state of next-generation influenza B vaccine development, including both advancements and challenges. This review covers the shortcomings of existing influenza vaccines and stresses the need for more-effective and broadly protective vaccines and more-easily scalable manufacturing processes. New possibilities for vaccine development have emerged due to recent technical developments such as virus-like particle (VLP) platforms, recombinant DNA technologies, and reverse genetics. By using these methods, vaccines can be developed that elicit stronger and longer-lasting immune responses against various strains of influenza B virus. Vaccines may be more effective and immunogenic when adjuvants and new delivery mechanisms are used. Progress has been made in the development of influenza B vaccine mRNA vaccines, nanoparticle-based vaccines, and vector-based vaccines. However, there are still several obstacles to overcome before next-generation influenza B vaccines can be widely used, including the challenge of antigenic drift, the extinction of the B/Yamagata lineage, and difficulties in strain selection. There are also other challenges related to public acceptance, vaccine distribution, manufacturing complexity, and regulations. To overcome these challenges, scientists, politicians, and pharmaceutical firms must work together to expedite the development and licensing of vaccines and the establishment of immunization programs. The need for constant monitoring and quick adaptation of vaccines to match the currently circulating strains is further highlighted by the appearance of novel influenza B virus variants. To be ready for future pandemics and influenza B outbreaks, we need better vaccines and better monitoring systems. [ABSTRACT FROM AUTHOR]

Objective: The authors sought to examine influenza and COVID-19 vaccine uptake among individuals diagnosed as having psychiatric disorders compared with those without such diagnoses and to examine variations in vaccine uptake by sociodemographic and clinical characteristics. Methods: The study was conducted in the Kaiser Permanente Georgia, Washington, and Southern California health care systems. Individuals with psychiatric conditions had at least one diagnosis of any psychiatric disorder during a 12-month study period; individuals in the control group had no psychiatric disorder diagnoses during this period, and the two groups were matched on age and sex. Bivariate analyses were conducted with Pearson chi-square tests; multivariate analyses were used to calculate the odds of receiving an influenza vaccine (N=1,307,202 individuals) or COVID-19 vaccine (N=1,380,894 individuals) and were controlled for selected covariates. Results: After controlling for relevant confounders, the authors found that having a diagnosis of any psychiatric illness was associated with significantly increased odds of receiving an influenza vaccine (OR=1.18; 95% CI=1.17–1.19, p<0.001), compared with no diagnosis of a psychiatric disorder. Having any psychiatric illness was associated with decreased odds of receiving a COVID-19 vaccine (OR=0.97; 95% CI=0.96–0.98, p<0.001), after the analysis was controlled for the same covariates. Conclusions: The findings provide evidence that people with mental health conditions were more likely to receive an influenza vaccine but were less likely to receive a COVID-19 vaccine, compared with individuals without such conditions. However, the vaccination rates observed for individuals with and without diagnosed psychiatric conditions were below national benchmarks, suggesting room for improving vaccine uptake in both patient populations. [ABSTRACT FROM AUTHOR]

Background: The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) that causes coronavirus disease 2019 (COVID-19) is a public health problem and may result in co-infection with other pathogens such as influenza virus. This review investigates the co-infection of SARS-CoV-2 and influenza A/B among patients with COVID-19. Methods: This meta- analysis included 38 primary studies investigating co-infection of SARS-CoV-2 with influenza in confirmed cases of COVID-19. The global online databases were used to identify relevant studies published between December 2019 and July 2024. Data analysis was performed using STATA Ver. 17 software, and standard errors of prevalence were calculated using the binomial distribution formula. Heterogeneity of study results was evaluated using the I-square and Q index, and publication bias was examined using the Begg's and Egger's tests, as well as funnel plot. A random effects model was used to determine prevalence rates, and a forest plot diagram was used to present results with 95% confidence intervals. In addition, sensitivity analyses were performed to check the impact of each primary study on the overall estimate. Result: The analysis found that the prevalence of influenza in co-infected patients at 95% confidence interval using a random effect model was 14% (95% CI: 8–20%). Significant heterogeneity was observed in the random-effects model for influenza A, 11% (95% CI: 5-18%) and B, 4% (95% CI: 2-7%) in co-infected patients. The highest prevalence of influenza A/B (21%), influenza A (17%) and influenza B (20%) was shown in Asia and Europe respectively. Subgroup analysis by study year showed that the co-prevalence of COVID-19 and influenza A/B was similar in the pre-2021 and post-2021 time periods, at 14% (95% CI: 5-23%) for pre-2021 and 6-22% for 2021 and post-2021. Also, the overall prevalence of influenza A and B in COVID-19 patients is 11% and 4%, and there was no significant difference between the time periods before and after 2021. Meta-regression with a random-effects model showed that the variables location, year group, and total patients showed only 2.71% of very high heterogeneity (I² = 99.92%), and none of these variables had a significant effect on the co-prevalence of COVID-19 and influenza A/B (p > 0.05). Also, meta-regression results showed that these variables had no significant effect on influenza A and B prevalence (p > 0.05) and showed only a small proportion of the very high heterogeneity (I² = 99.72%), (I² = 68.78%). In our study, Egger's test indicated that there was publication bias or small study effects in this meta-analysis (p = 0.0000). Conclusion: The combination of SARS-CoV-2 with influenza and other respiratory viruses requires the best treatment protocols to reduce the severity of the disease. In this approach, high vaccination coverage against seasonal influenza and SARS-CoV-2 could reduce the risk of co-infection in the recent pandemic. [ABSTRACT FROM AUTHOR]

In this paper, a delayed double-strain influenza model with vaccination and cross-immunity is proposed to explore the effect of coinfection of double-strain on disease spread. First, the nonnegativity and ultimate boundedness of solution are proved. Second, the basic reproduction numbers of strains 1, 2, and the whole model are defined respectively, by which criteria on the local and global asymptotic stability of (disease-free, dominant) equilibria are established. The uniform persistence of (strains 1, 2 coexistent) disease is obtained as well. Finally, the validity of the theoretical results is demonstrated by numerical simulations. We find that neglecting cross-immunity and vaccination would misestimate the size of influenza outbreaks. Cross-type multivalent vaccines will be the main direction for effective control measure for influenza. [ABSTRACT FROM AUTHOR]

One approach for developing a more universal influenza vaccine is to elicit strong immune responses against canonically immunosubdominant epitopes in the surface exposed viral glycoproteins. While standard vaccines typically induce responses directed primarily against mutable epitopes in the hemagglutinin (HA) head domain, there are generally limited or variable responses directed against epitopes in the relatively more conserved HA stalk domain and neuraminidase (NA) proteins. Here we describe a vaccine approach that utilizes a combination of wildtype (WT) influenza virus particles along with virus particles engineered to display a trimerized HA stalk in place of the full-length HA protein to elicit both responses simultaneously. After initially generating the "headless" HA-containing viral particles in the A/Hawaii/70/2019 (HI/19) genetic background and demonstrating the ability to elicit protective immune responses directed against the HA-stalk and NA, we co-formulated those virions with unmodified WT viral particles. The combination vaccine elicited "hybrid" and protective responses directed against the HA-head, HA-stalk, and NA proteins in both naïve and pre-immune mice and ferrets. Collectively, our results highlight a potentially generalizable method combining viral particles with differential antigenic compositions to elicit broader immune responses that may lead to more durable protection from influenza disease post-vaccination. Author summary: Influenza A virus infections remain a significant and persistent global challenge, as the viruses cause seasonal outbreaks and have pandemic-causing potential. Thus, improving the protection afforded by influenza vaccines is of high importance for human health. In this study we produced influenza viral particles that lack the classical immunodominant epitopes typically present in the head domain of the hemagglutinin (HA) protein. Vaccination with these modified virions allowed strong immune responses to develop against other protective viral epitopes, particularly within the relatively conserved HA stalk domain. We then showed that co-formulation of our engineered viral particles with unmodified virions allowed a "hybrid" vaccine response directed against all major viral epitopes of interest and provided protection from virally-induced disease. In ferrets with pre-existing influenza immunity, the experimental vaccine regimen also effectively elicited differential antibody profiles and allowed better control of infection in a heterologous viral challenge model. These data together suggest this approach has potential to serve as an improved, next-generation, influenza virus vaccine. [ABSTRACT FROM AUTHOR]

Introduction: Despite the efficacy and safety of SARS-CoV-2 vaccines, inflammatory and/or thrombotic episodes have been reported. Since the impact of COVID-19 vaccines on the endothelium remains uncertain, our objective was to assess endothelial activation status before and 90 days after the third dose of the BNT162b2 mRNA COVID-19 vaccine. Methods: A prospective longitudinal study was conducted at University General Hospital of Albacete, involving 38 healthy health-care workers. Serum levels of endothelial markers (endocan and sVCAM-1) and spike S1-specific IgG antibodies were determined before and at 7, 15, 24 and 90days following vaccination. To analyze each participant´s individual response, we calculated relative increases/decreases (delta values) in endothelial markers and antibodies concentrations compared to their pre-vaccination levels. Results: We identified two significantly distinct profiles of endothelial markers response, characterized by either increased or decreased serum levels of endocan and sVCAM. Incremental and decremental response groups did not differ in terms of age, sex, cardiovascular risk factors, previous SARS-CoV-2 infection and influenza vaccine co-administration. However, these responses were significantly associated with the relative spike-specific antibody production. Specifically, the greatest relative increase in antibodies was found in the decremental responders. Additionally, the higher delta antibody production was observed in non-previously infected individuals Conclusion: Administration of the BNT162b2 booster vaccine triggered a non-homogenous response of endothelial function markers among the study participants. Our findings improve the understanding of individual responses to the mRNA COVID-19 booster vaccine, which could be useful in assessing the need for booster doses, particularly in population at risk of vascular complications. [ABSTRACT FROM AUTHOR]

Introduction: Animal influenza viruses pose a danger to the general public. Eurasian avian-like H1N1 (EA H1N1) viruses have recently infected humans in several different countries and are often found in pigs in China, indicating that they have the potential to cause a pandemic. Therefore, there is an urgent need to develop a potent vaccine against EA H1N1. Methods: In this study, we report the effective intramuscular (i.m.) and/or intranasal (i.n.) vaccination of mice with a subunit influenza vaccine utilizing safe adjuvant gram-positive enhancer matrix (GEM) particles derived from the food-grade bacterium Lactococcus lactis. The hemagglutinin (HA)-protein anchor (PA) subunit vaccine can be simply mixed with GEM particles to produce vaccines. Results: After two booster injections, the i.m.+i.n. administered GEM subunit vaccine achieved hemagglutination inhibition titers in the serum that were equivalent to those observed using the conventional i.m. method. The mucosal and Th1-biased immune responses generated by the i.m. administered subunit vaccine alone were inferior to those induced by the i.n. and i.m.+i.n. administered subunit vaccines. Vaccinated mice were challenged with live viruses (G4 EA H1N1 and A/PR/8/34) to determine whether the adjuvant combination protected against the virus after vaccination with the influenza subunit vaccine. Compared to mice inoculated with HA alone, mice immunized with i.m.+i.n. or i.n. HA-PA-GEM displayed undetectable viral titers in the lungs, at 5 d after challenge. Discussion: Overall, this study not only offers other potential platforms for the generation of swine influenza vaccines, but also a theoretical foundation for vaccine vector platforms that can be utilized for future research on other infections. [ABSTRACT FROM AUTHOR]

Influenza vaccine effectiveness and immunogenicity can be compromised with repeated vaccination. We assessed immunological markers in a cohort of healthcare workers (HCW) from six public hospitals around Australia during 2020–2021. Sera were collected pre-vaccination and ~14 and ~180 days post-vaccination and assessed in haemagglutination inhibition assay against egg-grown vaccine and equivalent cell-grown viruses. Responses to vaccination were compared by the number of prior vaccinations. Baseline sera were available for 595 HCW in 2020 and 1031 in 2021. 5% had not been vaccinated during five years prior to enrolment and 55% had been vaccinated every year. Post-vaccination titres for all vaccine antigens were lowest among HCW vaccinated in all 5-prior years and highest among HCW with 0 or 1 prior vaccinations, even after adjustment. This was observed for both influenza A subtypes and was dependent on pre-vaccination titre. Expanded cohorts are needed to better understand how this translates to vaccine effectiveness. [ABSTRACT FROM AUTHOR]

The article focuses on the Advisory Committee on Immunization Practices' (ACIP) recommended immunization schedule for adults in the United States for 2025. Topics include updates to vaccine recommendations for COVID-19, influenza, and pneumococcal vaccines, changes to the immunization schedule format and guidance, and the inclusion of new vaccines such as the 21-valent pneumococcal conjugate vaccine and mRNA respiratory syncytial virus vaccine.

Background Pediatric hematopoietic cell transplant (HCT) recipients are at high risk for morbidity from influenza virus infection. We demonstrated in a primary phase 2 randomized controlled trial that 2 post-HCT doses of high-dose trivalent influenza vaccine (HD-TIV) given 4 weeks apart were more immunogenic than 2 doses of standard-dose quadrivalent influenza vaccine (SD-QIV). Herein, we present the immunogenicity and safety of influenza vaccination in a consecutive season post-HCT using the same dosing regimen. Methods A subcohort of study participants reenrolled and had hemagglutinin inhibition titers measured at baseline and 4 weeks after each vaccine dose in year 2. We estimated geometric mean fold rise in hemagglutinin inhibition titer from baseline for each group and used linear mixed effects models to estimate adjusted geometric mean ratios (comparing HD-TIV vs SD-QIV) for each antigen at each time point. We described systemic and injection site reactions. Results A total of 65 subcohort patients participated (33 SD-QIV, 32 HD-TIV). Postvaccine geometric mean fold rise and adjusted geometric mean ratio estimates were higher for both groups following a single influenza vaccine dose in year 2 as compared with 2 doses of the same formulation in year 1. Both groups had similar frequencies of injection site and systemic reactions. Conclusions A single dose of HD-TIV or SD-QIV was more immunogenic in year 2 than 2 doses of the same formulation in year 1. Reactogenicity was comparable between groups. One dose of influenza vaccine may be sufficient after a 2-dose schedule in the prior year post-HCT. Clinical Trials Registration NCT02860039 (ClinicalTrials.gov). [ABSTRACT FROM AUTHOR]

Background A single-dose investigational respiratory syncytial virus (RSV) vaccine, RSV prefusion protein F3 (RSVPreF3), was co-administered with a single-dose quadrivalent influenza vaccine (FLU-D-QIV) in a phase 3, randomized, controlled, multicenter study in healthy, nonpregnant women aged 18–49 years. Methods The study was observer-blind to evaluate the lot-to-lot consistency of RSVPreF3, and single-blind to evaluate the immune response, safety, and reactogenicity of RSVPreF3 co-administered with FLU-D-QIV. Results A total of 1415 participants were included in the per-protocol set. There was a robust immune response at day 31 across each of the 3 RSVPreF3 vaccine lots; adjusted geometric mean concentration ratios (95% confidence interval [CI]) were 1.01 (.91–1.12), 0.93 (.84–1.03), and 0.92 (.83–1.02) for RSV1/RSV2, RSV1/RSV3, and RSV2/RSV3, respectively. For FLU-D-QIV co-administered with RSVPreF3, versus FLU-D-QIV alone at day 31, noninferiority was satisfied for 3 of 4 strains assessed, with the lower limit of the 95% CI for geometric mean ratio >0.67. Conclusions Immunogenic consistency was demonstrated for 3 separate lots of RSVPreF3. Immunogenic noninferiority was demonstrated when comparing FLU-D-QIV administered alone, versus co-administered with RSVPreF3, for 3 strains of FLU-D-QIV. Co-administration was well tolerated, and both vaccines had clinically acceptable safety and reactogenicity profiles. Clinical Trials Registration NCT05045144; EudraCT 2021-000357-26. [ABSTRACT FROM AUTHOR]

Background Vaccination is the most effective way to prevent influenza infection and adverse outcomes; despite global recommendations to vaccinate pregnant persons, access to influenza vaccines remains low. We explored knowledge, attitudes, and practices of pregnant persons to inform actions to improve vaccine uptake. Methods We pooled data from cross-sectional surveys assessing pregnant persons' attitudes toward influenza vaccines in 8 low- and middle-income countries. Countries used standard methods to measure attitudes and intents toward influenza vaccination. We stratified by presence/absence of a national influenza vaccination program, income group, geographic region, and individual-level factors. Results Our analysis included 8556 pregnant persons from 8 countries. Most pregnant persons (6323, 74%) were willing to receive influenza vaccine if it was offered for free. Willingness differed by presence of an existing influenza vaccination program; acceptance was higher in countries without programs (2383, 89%) than in those with programs (3940, 67%, P <.001). Conclusions Most pregnant persons in middle-income countries, regardless of influenza vaccination program status, were willing to be vaccinated against influenza if the vaccine was provided free of charge. National investments in influenza vaccination programs present an opportunity to avert illness both in pregnant persons themselves and in their newborn babies. [ABSTRACT FROM AUTHOR]

Background Seasonal influenza remains a global public health concern. A messenger RNA (mRNA)–based quadrivalent seasonal influenza vaccine, mRNA-1010, was investigated in a first-in-human, phase 1/2 clinical trial conducted in 3 parts. Methods In parts 1 to 3 of this stratified observer-blind study, adults aged ≥18 years were randomly assigned to receive a single dose (6.25–200 µg) of mRNA-1010 or placebo (part 1) or an active comparator (Afluria; parts 2 and 3). Primary study objectives were assessment of safety, reactogenicity, and humoral immunogenicity of mRNA-1010, placebo (part 1), or active comparator (parts 2 and 3). Exploratory end points included assessment of cellular immunogenicity (part 1) and antigenic breadth against vaccine heterologous strains (A/H3N2; parts 1 and 2). Results In all study parts, solicited adverse reactions were reported more frequently for mRNA-1010 than placebo or Afluria, and most were grade 1 or 2 in severity. No vaccine-related serious adverse events or deaths were reported. In parts 1 and 2, a single dose of mRNA-1010 (25–200 µg) elicited robust day 29 hemagglutination inhibition titers that persisted through 6 months. In part 3, lower doses of mRNA-1010 (6.25–25 µg) elicited day 29 hemagglutination inhibition titers that were higher or comparable to those of Afluria for influenza A strains. When compared with Afluria, mRNA-1010 (50 µg) elicited broader A/H3N2 antibody responses (part 2). mRNA-1010 induced greater T-cell responses than placebo at day 8 that were sustained or stronger at day 29 (part 1). Conclusions Data support the continued development of mRNA-1010 as a seasonal influenza vaccine. Clinical Trials Registration NCT04956575 (https://clinicaltrials.gov/study/NCT04956575). [ABSTRACT FROM AUTHOR]

The efficacy of antibody responses is inherently linked to paratope diversity, as generated through V(D)J recombination and somatic hypermutation. Despite this, it is unclear how genetic diversification mechanisms evolved alongside codon optimality and affect antibody expression. Here, we analyze germline immunoglobulin (IG) genes, natural V(D)J repertoires, serum IgG, and monoclonal antibody (mAb) expression through the lens of codon optimality. Germline variable genes (IGV s) exhibit diverse optimality that is inversely related to mutability. Hypermutation deoptimizes heavy-chain (IGH) VDJ repertoires within human tonsils, bone marrow, lymph nodes (including SARS-CoV-2-specific clones), blood (HIV-1-specific clones), mice, and zebrafish. Analyses of mutation-affected codons show that targeting to complementarity-determining regions constrains deoptimization. Germline IGHV optimality correlates with serum variable fragment (VH) usage after influenza vaccination, while synonymous deoptimization attenuated mAb yield. These findings provide unanticipated insights into an antagonistic relationship between diversification mechanisms and codon optimality. Ultimately, the need for diversity takes precedence over that for the most optimal codon usage. [Display omitted] • Mutation potential antagonizes codon optimality within germline human IGV genes • Somatic hypermutation deoptimizes IGH VDJ sequences in humans, mice, and zebrafish • Mutational targeting to CDRs helps constrain deoptimization • Serum IgG-VH frequency reflects IGHV optimality, and deoptimization blunts mAb yield McGrath et al. investigate the evolutionary relationship between V(D)J mutability, somatic hypermutation, and codon optimality within immunoglobulin repertoires in order to gain a better understanding of how diversification mechanisms might impact antibody expression efficiency. [ABSTRACT FROM AUTHOR]

Evidence regarding the high-dose (HD) vaccine's relative vaccine effectiveness (rVE) and absolute benefit in reducing influenza-related hospitalizations compared to the standard-dose (SD) vaccine is warranted. We estimated the adjusted rVE and the number needed to vaccinate (NNV) of the HD vaccine compared to the SD vaccine among Clalit Health Services members aged ≥65 years. Among 418,603 and 393,125 members vaccinated in the 2022–2023 and 2023–2024 influenza seasons, the adjusted rVE was 27% (95% CI: −12% to 61%) for 2022–2023 and 7% (95% CI: −36% to 42%) for 2023–2024, with NNV to prevent one hospitalization event being 2262 (95% CI: 1004 to ∞) and 7662 (95% CI: 1293 to ∞), respectively. Even among the highest-risk subgroup, the NNV was 1289 (95% CI: 571 to ∞) for 2022–2023 and 4719 (95% CI: 797 to ∞) for 2023–2024. The HD vaccine exhibited a limited incremental benefit, even for individuals at the highest risk. [ABSTRACT FROM AUTHOR]

Influenza B viruses pose a significant threat to global public health, leading to severe respiratory infections in humans and, in some cases, death. During the last 50 years, influenza B viruses of two antigenically distinct lineages (termed 'Victoria' and 'Yamagata') have circulated in humans, necessitating two different influenza B vaccine strains. In this study, we devised a novel vaccine strategy involving reciprocal amino acid substitutions at sites where Victoria- and Yamagata-lineage viruses differ, leading to the generation of 'hybrid' vaccine viruses with the potential to protect against both lineages. Based on antigenic characterization, we selected two candidates and assessed their protective efficacy in a ferret model. Notably, both recombinant HA proteins conferred enhanced protection against heterologous challenges compared to their respective wild-type antigens. These findings show the potential of our novel strategy to develop cross-lineage protective influenza B virus vaccines. [ABSTRACT FROM AUTHOR]

Madin–Darby Canine Kidney (MDCK) cells are a key cell line for influenza vaccine production, due to their high viral yield and low mutation resistance. In our laboratory, we established a tertiary cell bank (called M60) using a standard MDCK cell line imported from American Type Culture Collection (ATCC) in the USA. Due to their controversial tumourigenicity, we domesticated non-tumourigenic MDCK cells (named CL23) for influenza vaccine production via monoclonal screening in the early stage of this study, and the screened CL23 cells were characterised based on their low proliferative capacity, which had certain limitations in terms of expanding their production during cell resuscitation. It was thus our objective to enhance the proliferation efficiency of MDCK cells for influenza vaccine production following cell resuscitation, with a view to improving the production of non-tumourigenic MDCK cells for vaccines and enhancing the production of influenza virus lysate vaccines from MDCK cells through genetic intervention. We concentrated on the protein thrombosponin-1 (THBS1), which was markedly differentiated in the proteomics data of the two MDCK cells. By integrating this finding with related studies, we were able to ascertain that THBS1 exerts a significant influence on the level of cell proliferation and apoptosis. Consequently, our objective was to investigate the impact of THBS1 expression on MDCK cell apoptosis by verifying the differences in THBS1 expression between the two MDCK cells and by interfering with THBS1 expression in the MDCK cells. We found that the knockdown of THBS1 significantly increased the proliferation and apoptosis of CL23 cells without causing significant changes in cell migration and invasion, and its overexpression significantly decreased the proliferation of M60 cells and increased cell migration, invasion, and apoptosis. In addition, the TGF-β/Smad pathway target genes transforming growth factor-β1 (TGF-β1), mothers against decapentaplegic homolog 2 (Smad2), and mothers against decapentaplegic homolog 3 (Smad3), were significantly down-regulated in CL23 cells after THBS1 knockdown and up-regulated in M60 cells after overexpression, with consistent expression identified at both the mRNA and protein levels. The treatment of cells with TGF-β activators and inhibitors further demonstrated that THBS1 regulated MDCK cell proliferation and apoptosis through the TGF-β/Smad signalling pathway. Finally, we found that THBS1 also regulated H1N1 influenza virus replication. These findings enable a comprehensive understanding of the regulatory mechanisms of THBS1 regarding MDCK cell proliferation and apoptosis functions and the effects of influenza virus replication. [ABSTRACT FROM AUTHOR]

Inclusion of additional influenza A/H3N2 strains in seasonal influenza vaccines could expand coverage against multiple, antigenically distinct, cocirculating A/H3N2 clades and potentially replace the no longer circulating B/Yamagata strain. We aimed to evaluate the safety and immunogenicity of three next-generation seasonal influenza mRNA vaccines with different compositions that encode for haemagglutinins of multiple A/H3N2 strains, with or without the B/Yamagata strain, in adults. This randomised, open-label, phase 1/2 trial enrolled healthy adults aged 50–75 years across 22 sites in the USA. Participants were randomly assigned (1:1:1:1:1:1:1) via interactive response technology to receive a single dose of mRNA-1011.1 (pentavalent; containing one additional A/H3N2 strain [Newcastle]), mRNA-1011.2 (quadrivalent; B/Yamagata replaced with one additional A/H3N2 strain [Newcastle]), mRNA-1012 at one of two dose levels (pentavalent; B/Yamagata replaced with two additional A/H3N2 strains [Newcastle and Hong Kong]), or one of three quadrivalent mRNA-1010 controls each encoding one of the A/H3N2 study strains. The primary outcomes were safety, evaluated in all randomly assigned participants who received a study vaccination (safety population), and reactogenicity, evaluated in all participants from the safety population who contributed any solicited adverse reaction data (solicited safety population). The secondary outcome was humoral immunogenicity of investigational mRNA vaccines at day 29 versus mRNA-1010 control vaccines based on haemagglutination inhibition antibody (HAI) assay in the per-protocol population. Here, we summarise findings from the planned interim analysis after participants had completed day 29. The study is registered with ClinicalTrials.gov , NCT05827068 , and is ongoing. Between March 27 and May 9, 2023, 1183 participants were screened for eligibility, 699 (59·1%) were randomly assigned, and 696 (58·8%) received vaccination (safety population, n=696; solicited safety population, n=694; per-protocol population, n=646). 382 (55%) of the 696 participants in the safety population self-reported as female and 314 (45%) as male. Frequencies of solicited adverse reactions were similar across vaccine groups; 551 (79%) of 694 participants reported at least one solicited adverse reaction within 7 days after vaccination and 83 (12%) of 696 participants reported at least one unsolicited adverse event within 28 days after vaccination. No vaccine-related serious adverse events or deaths were reported. All three next-generation influenza vaccines elicited robust antibody responses against vaccine-matched influenza A and B strains at day 29 that were generally similar to mRNA-1010 controls, and higher responses against additional A/H3N2 strains that were not included within respective mRNA-1010 controls. Day 29 geometric mean fold rises in HAI titres from day 1 against vaccine-matched A/H3N2 strains were 3·0 (95% CI 2·6–3·6; Darwin) and 3·1 (2·6–3·8; Newcastle) for mRNA-1011.1; 3·3 (2·7–4·1; Darwin) and 4·2 (3·4–5·2; Newcastle) for mRNA-1011.2; 3·4 (2·9–4·0; Darwin), 4·5 (3·6–5·5; Newcastle), and 5·1 (4·2–6·2; Hong Kong) for mRNA-1012 50·0 μg; and 2·6 (2·2–3·1; Darwin), 3·7 (3·0–4·6; Newcastle), and 4·1 (3·3–5·1; Hong Kong) for mRNA-1012 62·5 μg. Inclusion of additional A/H3N2 strains did not reduce responses against influenza A/H1N1 or influenza B strains, and removal of B/Yamagata did not affect responses to B/Victoria. These data support the continued clinical development of mRNA-based next-generation seasonal influenza vaccines with broadened influenza A/H3N2 strain coverage. Moderna. [ABSTRACT FROM AUTHOR]

Objectives: In 2014, New York City initiated a childcare influenza vaccine requirement to increase influenza vaccination rates among children aged 6-59 months attending city-regulated childcare, including prekindergarten. We evaluated the requirement's effect on vaccination rates in childcare-aged children in New York City. Methods: We examined influenza vaccination rates in children aged 6-59 months and by age groups of 1, 2, 3, and 4 years for 8 influenza seasons (2012-2013 through 2019-2020), representing 2 seasons before the requirement, 2 seasons during the requirement, 2 seasons after its suspension, and 2 seasons after its reinstatement. We also assessed rates in a comparison group of children aged 5-8 years. We performed a difference-in-differences analysis to compare rate differences in age groups when the requirement was and was not in effect. We considered P <.05 as significant based on the Wald χ2 test. Results: Influenza vaccination rates among children aged 6-59 months increased 3.7 percentage points (from 47.7% to 51.4%) by the requirement's second year and declined 6.7 percentage points to 44.7% after suspension. After reinstatement, rates increased 10.7 percentage points to 55.4%. Rate changes were most pronounced among 4-year-olds, increasing 12.7 percentage points (from 45.3% to 58.0%) by the requirement's second year, declining 14.1 percentage points to 43.9% after suspension, and increasing 22.2 percentage points to 66.1% after reinstatement. In the comparison group, rates increased 4.9 percentage points (from 36.5% to 41.4%) after reinstatement. Rates increased significantly among 4-year-olds before versus at the initial requirement and decreased significantly after suspension. After reinstatement, rates increased significantly among all groups except 1-year-olds. Conclusion: The New York City influenza vaccine requirement improved influenza vaccination rates among preschool-aged children, adding to the evidence base showing that vaccine requirements raise vaccination rates. [ABSTRACT FROM AUTHOR]

• Examined links between IL and 6 reactivity to influenza vaccine and inhibitory control using the well-validated go/no-go task. • We manipulated incentive type (i.e., social, monetary) and incentive magnitude (i.e., high, low) to assess whether IL-6 reactivity was differentially related to inhibitory control by incentive condition. • Performance on both high social (i.e., view close-other picture) and low monetary incentive trials benefitted from greater levels of IL-6 reactivity. • Mild fluctuations in IL-6 may selectively influence the valuation of incentives, depending on their social significance and magnitude. While the impact of chronic, low-grade inflammation on cognitive functioning is documented in the context of neurodegenerative disease, less is known about the association between acute increases in inflammation and cognitive functioning in daily life. This study investigated how changes in interleukin-6 (IL-6) levels were associated with performance on an inhibitory control task, the go/no-go task. We further examined whether the opportunity to earn different incentive types (social or monetary) and magnitudes (high or low) was associated with differential performance on the task, depending on IL-6 levels. Using a within-participant design, individuals completed an incentivized go/no-go task before and after receiving the annual influenza vaccine. Multilevel logistic regressions were performed on the trial-level data (N obs = 30,528). For no-go trials, we did not find significant associations in IL-6 reactivity and changes in trial accuracy between sessions. For go trials, we found significant differences in the associations between IL-6 reactivity and changes in accuracy as a function of the incentive condition. Notably, greater IL-6 reactivity was consistently associated with fewer omission errors (i.e., greater accuracy on go trials) on high-magnitude social incentives (i.e., viewing a picture of a close-other) when compared to both low-magnitude social and high-magnitude monetary incentives. Together, these results suggest that mild fluctuations in inflammation might alter the valuation of an incentive, and possibly a shift toward devoting greater attentional resources when a large social incentive is on the line. Overall, this study sheds light on how everyday, low-grade fluctuations in inflammation may influence cognitive abilities essential for daily life and effective inhibitory control. [ABSTRACT FROM AUTHOR]

Adult patients with chronic respiratory diseases (CRDs) are considered high risk group who are more likely to experience worse clinical outcomes if they acquire viral or bacterial infections. Vaccination is the best preventive tool to reduce the risk of infection and disease occurrence and to reduce the level of severity of complications associated with the various vaccine-preventable infections. These guidelines were developed by the Saudi Thoracic Society task force to emphasize the critical importance of improving the vaccine coverage rates in adult patients with CRD. They are intended to serve as a reference for healthcare practitioners managing CRD patients. The guidelines aimed to review the current knowledge related to vaccination efficacy in adult patients with CRD, based on the recent evidence and recommendations. Integrating the administration of the recommended vaccines in routine healthcare, such as during outpatient visits or before hospital discharge, is crucial for improving the vaccination rates in high-risk patients. The key strategies to address this public health priority include simplifying vaccination guidelines to enhance their accessibility and implementation by healthcare providers, increasing awareness in both the patients and healthcare providers that vaccines are not only intended for children. Additional strategies include maintaining continuous surveillance and advance research to discover novel vaccines. This approach aims to expand the range of preventable diseases and improve overall health and well-being. Vaccine hesitancy remains a significant challenge that necessitates a clear understanding of the community concerns. Providing appropriate education and communication, as well as addressing these concerns, are the crucial steps toward improving vaccine acceptance and uptake. By implementing these guidelines and multifaceted strategies, healthcare systems can optimize vaccine coverage and protection for patients with CRD, reduce the burden of vaccine-preventable complications, and improve the clinical outcomes in this vulnerable population. [ABSTRACT FROM AUTHOR]

Background: Influenza vaccination is free of charge for Danish citizens with acquired immunodeficiency but recommendations do not specifically target patients with cancer. This study investigated whether influenza vaccination reduces the main outcome of overall mortality and the secondary outcomes of influenza requiring treatment, pneumonia, myocardial infarction, stroke, heart failure, and venous thromboembolism in patients with cancer. Methods: This was a register‐based nationwide cohort study. Adjusted hazard ratios (aHRs) and 95% confidence intervals (95% CIs) for overall mortality and secondary outcomes were estimated using Cox proportional hazards models. Analyses were conducted separately for four subgroups: patients aged <65 years with solid tumors, patients aged ≥65 years with solid tumors, patients aged <65 years with hematological cancer, and patients aged ≥65 years with hematological cancer. Results: A total of 53,249 adult patients with solid tumors who received chemotherapy and 22,182 adult patients with hematological cancer were followed for up to five influenza seasons in the study period of 2007–2018. In the main analysis covering December–March, influenza vaccination was associated with reduced overall mortality in all four subgroups. The reduction was most pronounced in patients with hematological cancer aged <65 years (aHR, 0.66; 95% CI, 0.51–0.87) and smallest in patients with solid tumors aged <65 years (aHR, 0.91; 95% CI, 0.84–0.99). In sensitivity analyses covering January–March, the aHR was 0.87 (95% CI, 0.65–1.16) in patients with hematological cancer aged <65 years and 1.01 (95% CI, 0.92–1.10) in patients with solid tumors aged <65 years. Results for the secondary outcomes were inconclusive. Conclusions: The results of this study cannot reject that influenza vaccination reduces overall mortality in immunocompromised patients with cancer. The results must be interpreted with caution because of potential unmeasured confounding, which can result in the overestimation of influenza vaccine effectiveness. Influenza vaccination may reduce overall mortality in immunocompromised patients with cancer. The results must be interpreted with caution because of potential unmeasured confounding, which is likely to result in overestimating the effect of influenza vaccination. [ABSTRACT FROM AUTHOR]

Healthcare workers (HCWs) are a trusted source of vaccine-related information for patients and communities, but they can show hesitancy or reluctance towards vaccinations. The objective of our study was to investigate HCWs' sentiment and hesitancy towards vaccination, focusing on COVID-19 and influenza vaccination. A global cross-sectional study spanning four continents. Utilizing a web-based survey, we gathered responses from 7793 HCWs across twelve countries. We used Latent Class Analysis models to build response profiles for respondents. We employed multilevel multivariable logistic regression models to assess the impact of individual determinants and country contextual effects on change in vaccine sentiment (ChVS) and COVID-19 vaccine hesitancy (CoVH). HCWs exhibited high agreement on the safety, effectiveness, and usefulness of vaccines. However, 21% reported strong or moderate CoVH. Country contextual effects significantly influenced ChVS and CoVH, with variations observed across nations, accounting for 6% of global variance in both ChVS and CoVH. Individual factors such as educational level, fear of contracting COVID-19, knowledge of COVID 19 vaccines, CoVH, influenza vaccination behaviour and general confidence in vaccines significantly influenced ChVS. CoVH was related to profession, influenza vaccination behaviour, fear of COVID-19 and main information sources. Individual factors played a major role in determining change in vaccine sentiment and COVID-19 vaccine hesitancy, but they can be modulated by other contextual elements at the country level. There is a need for tailored, nation-specific strategies to address vaccine hesitancy and enhance vaccine confidence among HCWs. [ABSTRACT FROM AUTHOR]

Federal regulators recently authorised two vaccines designed to prevent infection with respiratory syncytial virus (RSV) for adults aged 60 or older. While some efforts have been made to study vaccine uptake thus far, few have studied this group's intentions to vaccinate, as well as potential barriers to vaccination. This omission is noteworthy as adults aged 60 or older may be at an increased risk of experiencing severe complications from RSV infection. We fielded a nationally representative survey of 1200 US adults (n = 362 aged 60+). Respondents aged 60 or older were asked a series of questions about their willingness to receive an RSV vaccine, vaccine safety, and efficacy attitudes, and their knowledge about vaccination eligibility. We find that a majority of seniors (53%) intend to refuse an RSV vaccine. As of late fall 2023, just 14% of those eligible had already received an RSV vaccine. Multivariate regression models suggest that belief in the safety and efficacy of the RSV vaccine, as well as previous flu and COVID-19 vaccine uptake, are associated with increased RSV vaccination intentions. We document high levels of RSV vaccine hesitancy among adults aged 60 or older and show that negative vaccine attitudes and non-vaccination behaviors motivate RSV vaccine refusal. Our work thereby raises the possibility that efforts to communicate the safety and efficacy of RSV vaccination may have beneficial effects on RSV vaccine uptake. [ABSTRACT FROM AUTHOR]

Universal Basic Income (UBI) policies have the potential to promote a wide range of public health objectives by providing those who qualify with direct cash payments. One overlooked mechanism of particular importance to health researchers is the possibility that guaranteed income might increase consultation of primary and preventive care (e.g., annual doctors' visits; regular vaccination against infectious disease) by providing people with both the time and monetary resources to do so, thereby improving general health. This study assesses the effects of an exogenous shock to Alaska's UBI payments to all state residents: a 2022 decision to reclassify dividend "energy relief" provisions as nontaxable (thereby increasing payments by approximately $2,000 inflation-adjusted dollars). It estimates quasi-experimental treatment effects (in 2022 vs. 2021) via mixed linear probability models that compare pre/post policy change in primary care seeking behavior in Alaska vs. the US adult population; controlling for respondent-level fixed effects and state-level random effects. Data were collected in 2021–2022, and analyzed in 2024. The likelihood that Alaskans sought primary care postreform (relative to beforehand) increased by 6pp, which was significantly greater than the same difference (2pp) observed across all other (non-UBI) US States (∆=4pp, p <0.01). The study provides suggestive evidence that comparatively fewer Alaskans had difficulty affording primary care during this period, with less-consistent evidence of increased flu vaccine uptake. Enhanced UBI payments ought to be thought about as a form of health policy, as they have the potential to advance a wide range of health objectives related to preventive care. [ABSTRACT FROM AUTHOR]

Objective: We explored HPV vaccine concerns and healthcare provider communication among Hispanic/Latinx hesitant parents during the COVID-19 pandemic, and how those concerns and provider communications compared for influenza and COVID-19 vaccines. As a secondary aim, we explored communication needs and strategies for these recommended vaccines. Design: We applied a concurrent, multi-method study design (survey and interview) with 23 Hispanic/Latinx American parents of adolescents aged 11–18 years. An inductive deductive thematic approach was used to interpret interview data. Descriptives were used to analyze survey data. Results: Overall, most parents (77%) perceived that their child was receiving too many vaccines. Regarding hesitancy for the HPV vaccine, major parental concerns related to vaccine effectiveness (83%), vaccine necessity (83%), and vaccine safety (80%). For the COVID vaccine, major concerns were the newness of vaccine (83%), vaccine safety (77%), low perceived effectiveness (77%), and low perceived need (77%). For influenza vaccines, major parental concerns were vaccine safety (73%), low perceived need (73%), and preference for natural over vaccine-induced immunity (73%). Parents had overall positive views towards vaccination. Some parents prioritized school-required vaccines, and others ranked the recommended vaccines- HPV, COVID-19, and influenza vaccines- for their children. They saw the benefits of recommended vaccines; however, there were concerns. The majority received a provider's recommendation for HPV vaccination for their child, while over half had not received a recommendation for COVID-19 and influenza vaccines. Recommended communication strategies were diverse with parents highlighting the need for providers to capitalize on waiting and clinic rooms to provide education. Conclusion: Healthcare providers should take advantage of missed opportunities, improve healthcare interactions with a strong recommendation and persistent communication, and offer diverse communication strategies and messaging for vaccines. Future work should further explore multi-vaccine concerns and how addressing these concerns through healthcare-provider communication could improve HPV vaccination along with COVID-19 and influenza vaccination. [ABSTRACT FROM AUTHOR]

Objective: To examine correlates of and barriers to COVID-19 vaccine initiation and intention among college students. Participants: 1,171 students attending a public university in the South. Methods: Multivariate logistic regression was used to assess the correlates of vaccine intention and initiation. Reasons for pursuing or foregoing vaccination were analyzed qualitatively using an inductive approach. Results: Among respondents, 44% had initiated vaccination, 38% intended to be vaccinated, and 18% were unsure about/unwilling to be vaccinated. Vaccine initiation and intention were both associated with 2019-2020 seasonal flu vaccination and political ideology, with conservative-leaning students having lower odds of vaccine initiation and of intention relative to liberal-leaning students. The most common reasons for vaccine initiation/intention and for vaccine hesitancy differed in frequency by political ideology. Conclusion: The most effective vaccine promotion strategies may be those tailored to different social groups, virus-related beliefs/perceptions, and the specific concerns of vaccine hesitant students. [ABSTRACT FROM AUTHOR]

The risk of severe outcomes of influenza increases during pregnancy. Whether vaccine-induced T cell memory-primed prepregnancy retains the ability to mediate protection during pregnancy, when systemic levels of several hormones with putative immunomodulatory functions are increased, is unknown. Here, using murine adoptive transfer systems and a translationally relevant model of cold-adapted live-attenuated influenza A virus vaccination, we show that preexisting virus-specific memory T cell responses are largely unaltered and highly protective against heterotypic viral challenges during pregnancy. Expression of the transcription factor T-bet, which is upregulated in antiviral T cells responding in pregnant mice, is critical in preventing hormone-associated gain of detrimental T helper type 2 (TH2) attributes reported in other settings. Beyond antiviral effects, preexisting vaccine-primed T cell immunity prevents metabolic dysfunction in gravid dams and adverse neonatal outcomes often associated with maternal influenza infection. These results demonstrate robust protection of the maternal-fetal unit from severe consequences of respiratory virus infection by preexisting T cell immunity. [ABSTRACT FROM AUTHOR]

Native Hawaiians and Pacific Islanders (NHPIs) in aggregate experience greater health burdens than non-Hispanic Whites, such as a higher incidence of cervical cancer and COVID-19. Given the importance of vaccinations in preventing and reducing the severity of diseases, such as the flu, cervical cancer, and COVID-19, the receipt of vaccines during childhood and adolescence is crucial. Therefore, this qualitative study aimed to explore the factors associated with NHPI parents' decisions regarding vaccinating their children with these elective vaccinations—that is, vaccinations not required for child care, preschool, or K-12 admissions in California but highly recommended. A total of 15 NHPI parents were recruited through a community-based organization. Semi-structured interviews explored parents' reasons for accepting or denying each vaccine for their child(ren). Results demonstrated variable acceptance of each vaccine, though consistent themes included protection and concerns over side effects. This study also found two general types of parents—those who treat vaccines the same and those with varying opinions about each vaccine. Results from this study demonstrate the family- and community-oriented nature of NHPI communities, suggesting that future interventions target not only parents but also their families and communities to cultivate vaccine acceptance through social networks. Furthermore, addressing all three vaccines during well-child visits may benefit parents who view each vaccine as separate entities with individual pros and cons. Such interventions could contribute toward reducing the burdens of particularly chronic health disparities. [ABSTRACT FROM AUTHOR]

Whereas the intranasally delivered influenza vaccines used in children affect transmission of influenza virus in the community as well as reducing illness, inactivated influenza vaccines administered by intramuscular injection do not prevent transmission and have a variable, sometimes low rate of vaccine effectiveness. Although mucosally administered vaccines have the potential to induce more protective immune response at the site of viral infection, quantitating such immune responses in large scale clinical trials and developing correlates of protection is challenging. Here we show that by using mathematical models immune responses measured in the blood after delivery of vaccine to the lungs by aerosol can predict immune responses in the respiratory tract in pigs. Additionally, these models can predict protection from influenza virus challenge despite lower levels of blood responses following aerosol immunization. However, the inclusion of immune responses measured in nasal swab eluates did not improve the predictive power of the model. Our models are an important first step, providing proof of principle that it is feasible to predict immune responses and protection in pigs. This approach now provides a path to develop correlates of protection for mucosally delivered vaccines in samples that are easily accessed in clinical trials. [ABSTRACT FROM AUTHOR]

Background/Objectives: An effective universal influenza vaccine is urgently needed to overcome the limitations of current seasonal influenza vaccines, which are ineffective against mismatched strains and unable to protect against pandemic influenza. Methods: In this study, bovine and human adenoviral vector-based vaccine platforms were utilized to express various combinations of antigens. These included the H5N1 hemagglutinin (HA) stem region or HA2, the extracellular domain of matrix protein 2 of influenza A virus, HA signal peptide (SP), trimerization domain, excretory peptide, and the autophagy-inducing peptide C5 (AIP-C5). The goal was to identify the optimal combination for enhanced immune responses and cross-protection. Mice were immunized using a prime-boost strategy with heterologous adenoviral (Ad) vectors. Results: The heterologous Ad vectors induced robust HA stem-specific humoral and cellular immune responses in the immunized mice. Among the tested combinations, Ad vectors expressing SP + HA stem + AIP-C5 conferred significant protection against group 1 (H1N1 and H5N1) and group 2 (H3N2) influenza A viruses. This protection was demonstrated by lower lung viral titers and reduced morbidity and mortality. Conclusions: The findings support further investigation of heterologous Ad vaccine platforms expressing SP + HA stem + AIP-C5. This combination shows promise as a potential universal influenza vaccine, providing broader protection against influenza A viruses. [ABSTRACT FROM AUTHOR]

Background: The Influenza A virus (IAV), a pathogen affecting the respiratory system, represents a major risk to public health worldwide. Immunization remains the foremost strategy to control the transmission of IAV. The virus has two primary antigens: hemagglutinin (HA) and neuraminidase (NA). Our previous studies have demonstrated that an IAV NA mRNA vaccine can induce Th1-type immune responses in mice. This research examined the immune responses elicited by an mRNA vaccine targeting both HA and NA antigens in murine models. Methods: In this study, we used two dual-antigen immunization strategies: single-site immunization with an IAV HA+NA mRNA vaccine and multi-site immunization with an IAV HA mRNA vaccine and IAV NA mRNA vaccine. Hemagglutination-inhibiting antibody titer and neutralizing antibody titer in the sera of immunized mice were evaluated, and a viral challenge experiment was conducted. Additionally, the immune responses elicited by the two immunization strategies were characterized using flow cytometry and ELISA. Comparative analyses were performed with mice immunized individually with the IAV HA mRNA vaccine, IAV NA mRNA vaccine, and inactivated vaccine. Results: The results showed that by using a multi-site immunization strategy, mice were able to generate higher levels of hemagglutination-inhibiting and neutralizing antibodies, and were protected in a viral challenge experiment. Moreover, the multi-site regimen also promoted the generation of cytotoxic T cells and maintained a balanced Th1/Th2 immune response. Conclusions: Using mRNA vaccine based on a HA and NA antigen with multi-site immunization strategy can induce higher levels of hemagglutination-inhibiting and neutralizing antibodies, and multi-type immune responses in mice, providing new theoretical and experimental support for advancing upcoming influenza vaccines. [ABSTRACT FROM AUTHOR]