Computational detection of antigen-specific B cell receptors following immunization.

B cell receptors (BCRs) play a crucial role in recognizing and fighting foreign antigens. High-throughput sequencing enables in-depth sampling of the BCRs repertoire after immunization. However, only a minor fraction of BCRs actively participate in any given infection. To what extent can we accurately identify antigen-specific sequences directly from BCRs repertoires? We present a computational method grounded on sequence similarity, aimed at identifying statistically significant responsive BCRs. This method leverages well-known characteristics of affinity maturation and expected diversity. We validate its effectiveness using longitudinally sampled human immune repertoire data following influenza vaccination and SARS-CoV-2 infections. We show that different lineages converge to the same responding Complementarity Determining Region 3, demonstrating convergent selection within an individual. The outcomes of this method hold promise for application in vaccine development, personalized medicine, and antibody-derived therapeutics.

Hemagglutinin stalk-specific Fc-mediated functions are associated with protection against influenza-illness after seasonal influenza vaccination in pregnant women.

BACKGROUND: Several influenza vaccine candidates aim to elicit antibodies against the conserved hemagglutinin stalk domain. Understanding the protective mechanism of these antibodies, which mediate broad neutralization and Fc-mediated functions, following seasonal vaccination is critical. METHODS: Plasma samples were obtained from a subset of pregnant women living with or without HIV-1 enrolled in a randomised trial (138 trivalent inactivated vaccine [TIV] and 145 placebo recipients). Twenty-three influenza-illness cases were confirmed within 6 months postpartum. We measured H1 stalk-specific antibody-dependent cellular phagocytosis (ADCP), complement deposition (ADCD) and cellular cytotoxicity (ADCC) at enrolment and 1-month post-vaccination. The association between these Fc-mediated functions and protection against influenza-illness following vaccination was examined using multiple logistic regression analysis and risk reduction thresholds were defined by the score associated with the lowest odds of influenza-illness. RESULTS: Amongst TIV and placebo recipients, lower H1 stalk-specific ADCP and ADCD activity was detected for participants with confirmed influenza compared with individuals without confirmed influenza-illness 1-month post-vaccination. Pre-existing ADCP scores ≥250 reduced the odds of A/H1N1 infection (odds ratio 0.11; p=0.01) with an 83% likelihood of risk reduction. Following TIV, ADCD scores of ≥25 and ≥15 significantly reduced the odds against A/H1N1 (0.10; p=0.01) and non-group 1 (0.06; p=0.0004) influenza virus infections, respectively. These ADCD scores were associated with >84% likelihood of risk reduction. H1 stalk-specific ADCC potential was not associated with protection against influenza-illness. CONCLUSION: H1 stalk-specific ADCD correlates with protection against influenza-illness following influenza vaccination during pregnancy. These findings provide insight into the protective mechanisms of HA stalk antibodies.

Phase 3 Study Assessing Lot-to-lot Consistency of RSVPreF3 Vaccine and its Immune Response, Safety, and Reactogenicity When Co-administered with FLU-D-QIV.

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, non-pregnant 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 (0.91, 1.12), 0.93 (0.84, 1.03), and 0.92 (0.83, 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.

This was a phase 3 study that compared antibodies against respiratory syncytial virus (or RSV for short) between women who were given 3 different production batches of RSV prefusion protein F3 (known as RSVPreF3) vaccine. The study also compared the antibodies between women who received either an RSV vaccine together with a flu vaccine (known as FLU-D-QIV), or a flu vaccine alone. The flu vaccine contained 4 different strains of flu virus. The study involved 1415 healthy, non-pregnant women aged 18­49 years. The antibodies checked after 31 days showed strong immune responses for all 3 RSV vaccine production batches, and similar immune responses between each of the 3 RSV vaccine production batches. The immune response of 3 of the 4 flu strains was not less when the flu vaccine was given together with the RSV vaccine than the immune response when flu vaccine was given alone and both vaccines were well tolerated.

Safety and Immunogenicity of Respiratory Syncytial Virus Prefusion F Protein Vaccine when Co-administered with Adjuvanted Seasonal Quadrivalent Influenza Vaccine in Older Adults: A Phase 3 Randomized Trial.

BACKGROUND: We evaluated co-administration of adjuvanted seasonal quadrivalent influenza vaccine (FLU-aQIV) and respiratory syncytial virus (RSV) prefusion F protein-based vaccine (RSVPreF3 OA) in ≥65-year-olds. METHODS: This phase 3, open-label trial randomized ≥65-year-olds to receive FLU-aQIV and RSVPreF3 OA concomitantly (Co-Ad) or sequentially, 1 month apart (Control). Primary objectives were to demonstrate the non-inferiority of FLU-aQIV and RSVPreF3 OA co-administration versus sequential administration in terms of hemagglutination inhibition (HI) titers for each FLU-aQIV strain and RSV-A and RSV-B neutralization titers, 1 month post-vaccination. Reactogenicity and safety were also assessed. RESULTS: Overall, 1045 participants were vaccinated (Co-Ad: 523; Control: 522). Non-inferiority of FLU-aQIV and RSVPreF3 OA co-administration versus sequential administration was demonstrated in terms of HI titers for the A/Victoria(H1N1), B/Victoria, and B/Yamagata influenza strains and RSV-A neutralization titers (upper limits [ULs] of 95% confidence intervals [CIs] for adjusted geometric mean titer [GMT] ratios [Control/Co-Ad] ≤1.50) but not for A/Darwin(H3N2) HI titers (95% CI UL = 1.53). The immune response to A/Darwin(H3N2) was further assessed post-hoc using a microneutralization assay; the post-vaccination adjusted GMT ratio (Control/Co-Ad) was 1.23 (95% CI: 1.06-1.42, ie, UL ≤1.50), suggesting an adequate immune response to A/Darwin(H3N2) following co-administration. RSV-B neutralization titers were comparable between groups (95% CI UL for adjusted GMT ratio ≤1.50). Solicited adverse events were mostly mild or moderate and transient; unsolicited and serious adverse event rates were balanced between groups. CONCLUSIONS: Adjuvanted FLU-aQIV and RSVPreF3 OA had acceptable reactogenicity/safety profiles when co-administered in ≥65-year-olds, without clinically relevant interference with the immune responses to either vaccine. CLINICAL TRIALS REGISTRATION: NCT05568797.

Cost-effectiveness analysis of cell-based versus egg-based quadrivalent influenza vaccines in the pediatric population in Taiwan.

Cell-based influenza vaccines avoid egg-adaptive mutations, potentially improving vaccine effectiveness. We assessed the one-season cost-effectiveness of cell-based quadrivalent influenza vaccine (QIVc) against that of egg-derived quadrivalent influenza vaccines (QIVe) in children (6 months to 17 years of age) from payer and societal perspectives in Taiwan using an age-stratified static model. Base case and high egg adaptation scenarios were assessed. Deterministic and probabilistic sensitivity analyses were performed. The incremental cost-effectiveness ratio (ICER) threshold in Taiwan was assumed to be USD 99 177/quality-adjusted life year (QALY). Compared to QIVe, QIVc would prevent 15 665 influenza cases, 2244 complicated cases, and 259 hospitalizations per year. The base case ICER was USD 68 298/QALY and USD 40 085/QALY from the payer and societal perspective, respectively. In the high egg adaptation scenario, the ICER was USD 45 782/QALY from the payer's perspective and USD 17 489/QALY from the societal perspective. Deterministic sensitivity analyses indicated that infection incidence rate, vaccination coverage, and prevalence of the A/H3N2 strain were the main drivers of ICER. In conclusion, switching the immunization strategy from QIVe to QIVc is predicted to reduce the influenza-associated disease burden and be cost-effective for the pediatric population in Taiwan. The potential benefits of QIVc would be even higher during influenza seasons with high levels of egg adaptation.

Vaccination against influenza viruses reduces infection, not hospitalization or death, from respiratory COVID-19: A systematic review and meta-analysis.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causes COVID-19 and has brought a huge burden in terms of human lives. Strict social distance and influenza vaccination have been recommended to avoid co-infections between influenza viruses and SARS-CoV-2. Scattered reports suggested a protective effect of influenza vaccine on COVID-19 development and severity. We analyzed 51 studies on the capacity of influenza vaccination to affect infection with SARS-CoV-2, hospitalization, admission to Intensive Care Units (ICU), and mortality. All subjects taken into consideration did not receive any anti-SARS-CoV-2 vaccine, although their status with respect to previous infections with SARS-CoV-2 is not known. Comparison between vaccinated and not-vaccinated subjects for each of the four endpoints was expressed as odds ratio (OR), with 95% confidence intervals (CIs); all analyses were performed by DerSimonian and Laird model, and Hartung-Knapp model when studies were less than 10. In a total of 61 029 936 subjects from 33 studies, influenza vaccination reduced frequency of SARS-CoV-2 infection [OR plus 95% CI = 0.70 (0.65-0.77)]. The effect was significant in all studies together, in health care workers and in the general population; distance from influenza vaccination and the type of vaccine were also of importance. In 98 174 subjects from 11 studies, frequency of ICU admission was reduced with influenza vaccination [OR (95% CI) = 0.71 (0.54-0.94)]; the effect was significant in all studies together, in pregnant women and in hospitalized subjects. In contrast, in 4 737 328 subjects from 14 studies hospitalization was not modified [OR (95% CI) = 1.05 (0.82-1.35)], and in 4 139 660 subjects from 19 studies, mortality was not modified [OR (95% CI) = 0.76 (0.26-2.20)]. Our study emphasizes the importance of influenza vaccination in the protection against SARS-CoV-2 infection.

Effectiveness of patient reminders on influenza vaccination coverage among adults with chronic conditions: A feasibility study in Australian general practices.

BACKGROUND: Influenza vaccination is recommended for Australians 18+ years old with medical risk factors, but coverage is suboptimal. We aimed to examine whether automatic, opportunistic patient reminders (SMS and/or printed) before appointments with a general practitioner increased influenza vaccination uptake. METHODS: This clustered non-randomised feasibility study in Australian general practice included patients aged 18-64 years with at least one medical risk factor attending participating practices between May and September 2021. Software installed at intervention practices identified unvaccinated eligible patients when they booked an appointment, sent vaccination reminders (SMS on booking and 1 h before appointments), and printed automatic reminders on arrival. Control practices provided usual care. Clustered analyses adjusted for sociodemographic differences among practices were performed using logistic regression. RESULTS: A total of 12,786 at-risk adults attended 16 intervention practices (received reminders = 4066; 'internal control' receiving usual care = 8720), and 5082 individuals attended eight control practices. Baseline influenza vaccination uptake (2020) was similar in intervention and control practices (∼34%). After the intervention, uptake was similar in all groups (control practices = 29.3%; internal control = 30.0%; intervention = 31.6% (p-value = 0.203). However, SMS 1 h before appointments increased vaccination coverage (39.3%, adjusted OR = 1.65; 95%CI 1.20;2.27; number necessary to treat = 13), especially when combined with other reminder forms. That effect was more evident among adults with chronic respiratory, rheumatologic, or inflammatory bowel disease. CONCLUSION: These findings indicate that automated SMS reminders delivered at proximate times to appointments are a low-cost strategy to increase influenza vaccination among adults at higher risk of severe disease attending Australian general practices.

Immune cell receptor-specific nanoparticles as a potent adjuvant for nasal split influenza vaccine delivery.

Mucosal delivery systems have gained much attention as effective way for antigen delivery that induces both systemic and mucosal immunity. However, mucosal vaccination faces the challenges of mucus barrier and effective antigen uptake and presentation. In particular, split, subunit and recombinant protein vaccines that do not have an intact pathogen structure lack the efficiency to stimulate mucosal immunity. In this study, poly (lactic acid-co-glycolic acid-polyethylene glycol) (PLGA-PEG) block copolymers were modified by mannose to form a PLGA-PEG-Man conjugate (mannose modified PLGA-PEG), which were characterized. The novel nanoparticles (NPs) prepared with this material had a particle size of about 150 nm and a zeta potential of -15 mV, and possessed ideal mucus permeability, immune cell targeting, stability and low toxicity. Finally, PLGA-PEG-Man nanoparticles (PLGA-PEG-Man NPs) were successfully applied for intranasal delivery of split influenza vaccine in rat for the first time, which triggered strong systemic and mucosal immune responses. These studies suggest that PLGA-PEG-Man NPs could function as competitive potential nano-adjuvants to address the challenge of inefficient mucosal delivery of non-allopathogenic antigens.

Strategies to increase the coverage of influenza and pneumonia vaccination in older adults: a systematic review and network meta-analysis.

BACKGROUND: It is urgent to implement interventions to increase vaccination rates of influenza/pneumonia vaccines in older adults, yet the effectiveness of different intervention strategies has not been thoroughly evaluated. OBJECTIVE: We aimed to assess the effectiveness of intervention strategies for increasing the coverage of influenza/pneumonia vaccination in older adults. METHODS: PubMed, Web of Science, Cochrane Library, Embase, China Biology Medicine disc, China National Knowledge Infrastructure and Wanfang were searched from 1 January 2000 to 1 October 2022. RCTs that assessed any intervention strategies for increasing influenza/pneumonia vaccination coverage or willingness in older adults were included. A series of random-effects network meta-analysis was conducted by using frequentist frameworks. RESULTS: Twenty-two RCTs involving 385,182 older participants were eligible for further analysis. Eight types of intervention strategies were evaluated. Compared with routine notification, health education (odds ratio [OR], 1.85 [95%CI, 1.19 to 2.88]), centralised reminder (OR, 1.63 [95%CI, 1.07 to 2.47]), health education + onsite vaccination (OR, 2.89 [95%CI, 1.30 to 6.39]), and health education + centralised reminder + onsite vaccination (OR, 20.76 [95%CI, 7.33 to 58.74]) could effectively improve the vaccination rate. The evidence grade was low or very low due to the substantial heterogeneity among studies. CONCLUSIONS: Our findings suggest that health education + centralised reminder + onsite vaccination may potentially be an effective strategy regardless of cost, but the evidence level was low. More rigorous trials are needed to identify the association between strategies and vaccination rates among older adults and to integrate such evidence into clinical care to improve vaccination rates.

Influenza vaccine uptake in juvenile idiopathic arthritis: a multi-centre cross-sectional study.

While most countries provide safe and effective influenza vaccines for at-risk groups, influenza vaccine coverage among children with rheumatic diseases remains uncertain. This study investigated influenza vaccination rates in children with juvenile idiopathic arthritis (JIA) during the 2019-2020 season and assessed the knowledge and attitudes of caregivers of children with JIA regarding influenza vaccination. The secondary aims were to identify barriers to vaccination and explore strategies to improve vaccination rates. A multi-centre, cross-sectional anonymous survey was conducted in 7 countries during the 2019-2020 influenza season to assess the uptake history of influenza vaccination. Among 287 participants, only 87 (30%) children with JIA received the influenza vaccine during the 2019-2020 season. Children who were more likely to be vaccinated were those with systemic juvenile idiopathic arthritis (sJIA), a history of previous vaccination and those aware of the vaccination recommendations. Conversely, children who previously experienced adverse vaccine-related events reported the lowest uptake. The primary reason for non-vaccination was lack of awareness about the necessity of influenza vaccination.  Conclusion: Despite variations among countries, the uptake of influenza vaccines remains low in children with JIA. Improving awareness among families about the importance of influenza vaccination may increase vaccination rates in children with rheumatic diseases. What is Known: • Rheumatic children are at increased risk for influenza infection due to immunosuppressive therapy and immune dysregulation. • Influenza vaccine is formally recommended to children with rheumatic diseases. What is New: • This multicentre study showed that influenza vaccine uptake rates remain suboptimal among children with Juvenile Idiopathic Arthritis despite formal recommendations. • Factors like previous experience with vaccination and information provided by medical professionals via different ways play essential roles in increasing vaccination rates and can contribute to improved health outcomes for these vulnerable children.

Interim Estimates of 2023-2024 Seasonal Influenza Vaccine Effectiveness Among Adults in Korea.

In the 2023-2024 season, the influenza epidemic in South Korea peaked earlier than in recent years. In this study, we aimed to estimate the interim vaccine effectiveness (VE) of the influenza vaccination to prevent influenza during the early season. From November 1, 2023, to December 31, 2023, we enrolled 2,632 subjects with influenza-like illness from eight hospitals participating in hospital-based influenza morbidity and mortality surveillance. A retrospective test-negative case-control study was conducted to estimate the VE. The results showed an adjusted VE of 22.5% (95% confidence interval [CI], 6.6 to 35.8) for the total population. The adjusted VE was 22.3% (95% CI, 6.1 to 35.7) for influenza A and 9.4% (95% CI, -51.3 to 45.7) for influenza A/H1N1. Full results of the analysis will be reported.

Lessons learned from annotation of VAERS reports on adverse events following influenza vaccination and related to Guillain-Barré syndrome.

BACKGROUND: Vaccine Adverse Events ReportingSystem (VAERS) is a promising resource of tracking adverse events following immunization. Medical Dictionary for Regulatory Activities (MedDRA) terminology used for coding adverse events in VAERS reports has several limitations. We focus on developing an automated system for semantic extraction of adverse events following vaccination and their temporal relationships for a better understanding of VAERS data and its integration into other applications. The aim of the present studyis to summarize the lessons learned during the initial phase of this project in annotating adverse events following influenza vaccination and related to Guillain-Barré syndrome (GBS). We emphasize on identifying the limitations of VAERS and MedDRA. RESULTS: We collected 282 VAERS reports documented between 1990 and 2016 and shortlisted those with at least 1,100 characters in the report. We used a subset of 50 reports for the preliminary investigation and annotated all adverse events following influenza vaccination by mapping to representative MedDRA terms. Associated time expressions were annotated when available. We used 16 System Organ Class (SOC) level MedDRA terms to map GBS related adverse events and expanded some SOC terms to Lowest Level Terms (LLT) for granular representation. We annotated three broad categories of events such as problems, clinical investigations, and treatments/procedures. The inter-annotator agreement of events achieved was 86%. Incomplete reports, typographical errors, lack of clarity and coherence, repeated texts, unavailability of associated temporal information, difficulty to interpret due to incorrect grammar, use of generalized terms to describe adverse events / symptoms, uncommon abbreviations, difficulty annotating multiple events with a conjunction / common phrase, irrelevant historical events and coexisting events were some of the challenges encountered. Some of the limitations we noted are in agreement with previous reports. CONCLUSIONS: We reported the challenges encountered and lessons learned during annotation of adverse events in VAERS reports following influenza vaccination and related to GBS. Though the challenges may be due to the inevitable limitations of public reporting systems and widely reported limitations of MedDRA, we emphasize the need to understand these limitations and extraction of other supportive information for a better understanding of adverse events following vaccination.

The economic and fiscal impact of incremental use of cell-based quadrivalent influenza vaccine for the prevention of seasonal influenza among healthcare workers in Italy.

BACKGROUND: Seasonal influenza has a significant impact on public health, generating substantial direct healthcare costs, production losses and fiscal effects. Understanding these consequences is crucial to effective decision-making and the development of preventive strategies. This study aimed to evaluate the economic and the fiscal impact of implementing an incremental strategy for seasonal influenza prevention using the cell-based quadrivalent influenza vaccine (QIVc) among healthcare workers (HCWs) in Italy. METHODS: To estimate the economic impact of implementing this strategy, we performed a cost analysis that considered direct healthcare costs, productivity losses and fiscal impact. The analysis considered a 3-year time horizon. A deterministic sensitivity analysis was also conducted. RESULTS: Assuming a vaccination coverage rate of 30% among HCWs, the analysis considered a total of 203 018 vaccinated subjects. On analysing the overall differential impact (including direct costs, indirect costs and fiscal impact), implementing QIVc vaccination as a preventative measure against influenza among HCWs in Italy would yield societal resource savings of €23 638.78 in the first year, €47 277.56 in the second year, and €70 916.35 in the third year, resulting in total resource savings of €141 832.69. CONCLUSIONS: The study demonstrated that implementing the incremental use of QIVc as part of a preventive strategy for seasonal influenza among HCWs in Italy could yield positive economic outcomes, especially in terms of indirect costs and fiscal impact. The resources saved could be utilized to fund further public health interventions. Policy-makers should consider these findings when making decisions regarding influenza prevention strategies targeting HCWs.

Measuring waning protection from seasonal influenza vaccination during nine influenza seasons, Ontario, Canada, 2010/11 to 2018/19.

BackgroundWaning immunity from seasonal influenza vaccination can cause suboptimal protection during peak influenza activity. However, vaccine effectiveness studies assessing waning immunity using vaccinated and unvaccinated individuals are subject to biases.AimWe examined the association between time since vaccination and laboratory-confirmed influenza to assess the change in influenza vaccine protection over time.MethodsUsing linked laboratory and health administrative databases in Ontario, Canada, we identified community-dwelling individuals aged ≥ 6 months who received an influenza vaccine before being tested for influenza by RT-PCR during the 2010/11 to 2018/19 influenza seasons. We estimated the adjusted odds ratio (aOR) for laboratory-confirmed influenza by time since vaccination (categorised into intervals) and for every 28 days.ResultsThere were 53,065 individuals who were vaccinated before testing for influenza, with 10,264 (19%) influenza-positive cases. The odds of influenza increased from 1.05 (95% CI: 0.91-1.22) at 42-69 days after vaccination and peaked at 1.27 (95% CI: 1.04-1.55) at 126-153 days when compared with the reference interval (14-41 days). This corresponded to 1.09-times increased odds of influenza every 28 days (aOR = 1.09; 95% CI: 1.04-1.15). Individuals aged 18-64 years showed the greatest decline in protection against influenza A(H1N1) (aORper 28 days = 1.26; 95% CI: 0.97-1.64), whereas for individuals aged ≥ 65 years, it was against influenza A(H3N2) (aORper 28 days = 1.20; 95% CI: 1.08-1.33). We did not observe evidence of waning vaccine protection for individuals aged < 18 years.ConclusionsInfluenza vaccine protection wanes during an influenza season. Understanding the optimal timing of vaccination could ensure robust protection during seasonal influenza activity.

Comparing higher-dose and single standard-dose influenza vaccines in preventing cardiovascular events: a meta-analysis with 68,713 patients.

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

Pediatric practice experiences with second dose influenza vaccination: An AAP Pediatric Research in Office Settings (PROS) Study.

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

Influenza and Covid-19 Vaccination in 2023: a descriptive analysis in two Italian Research and Teaching Hospitals. Is the On-Site strategy effective?

Introduction: Vaccinations represent an extremely effective tool for the prevention of certain infectious diseases - such as influenza and COVID-19 -, particularly for those categories at risk due to both their frail condition or professional exposure, such as healthcare workers. The aim of this study is to describe the course of the anti-influenza and anti-COVID-19 vaccination campaign at two Research Hospitals in Milan, Italy. Study design: Multicentre, cross-sectional study. Methods: For the 2023-24 vaccination campaign, the two facilities opted for two different approaches. At the Hospital A, two dif-ferent strategies for vaccinating healthcare workers were implemented: a fixed-site vaccination clinic and two mobile vaccination groups run by Public Health residents of the University of Milan. At the Hospital B, on the other hand, a single fixed-site outpatient clinic run by Public Health residents of the University of Milan was used. On the occasion of the campaign, a survey was also carried out using anonymous online questionnaires to investigate healthcare workers attitudes towards vaccination. Results: A total of 1,937 healthcare workers were vaccinated: 756 were immunized against influenza only, 99 against COVID-19 only, and 1,082 against both. The results show a substantial difference in vaccination adherence among medical and nursing staff compared to other professional categories. In particular, the category with the highest vaccination adhesion turned out to be that of medical doctors with 55.7% adhesion while, on the contrary, the category with the lowest adhesion turned out to be that of auxiliary personnel characterized by 7.4% adhesion. At the same time, the comparison between the two hospital facilities showed a double adherence rate by the staff of Hospital A as regards both the flu vaccine (40.6% and 20.1%) and the anti-COVID-19 vaccine (26.4% and 12.3%). Finally, the survey showed that the attitude towards influenza vaccination is lower among auxiliary staff in terms of both knowledge and vaccination attitude. Conclusions: The results of the study show a vaccination adherence in line with that of previous years, although lower than the values recommended by the principal national and international Organizations. The analysis of the differences between the two facilities and the surveys carried out will allow for the implementation of targeted interventions to increase adherence in future campaigns.

Intratumoral Influenza Vaccine Administration Attenuates Breast Cancer Growth and Restructures the Tumor Microenvironment through Sialic Acid Binding of Vaccine Hemagglutinin.

Breast cancer continues to have a high disease burden worldwide and presents an urgent need for novel therapeutic strategies to improve outcomes. The influenza vaccine offers a unique approach to enhance the anti-tumor immune response in patients with breast cancer. Our study explores the intratumoral use of the influenza vaccine in a triple-negative 4T1 mouse model of breast cancer. We show that the influenza vaccine attenuated tumor growth using a three-dose intratumoral regimen. More importantly, prior vaccination did not alter this improved anti-tumor response. Furthermore, we characterized the effect that the influenza vaccine has on the tumor microenvironment and the underlying mechanisms of action. We established that the vaccine facilitated favorable shifts in restructuring the tumor microenvironment. Additionally, we show that the vaccine's ability to bind sialic acid residues, which have been implicated in having oncogenic functions, emerged as a key mechanism of action. Influenza hemagglutinin demonstrated binding ability to breast cancer cells through sialic acid expression. When administered intratumorally, the influenza vaccine offers a promising therapeutic strategy for breast cancer patients by reshaping the tumor microenvironment and modestly suppressing tumor growth. Its interaction with sialic acids has implications for effective therapeutic application and future research.

[Application and prospect of natural active ingredients of traditional Chinese medicine in immunological adjuvant for influenza vaccine].

Vaccination is an effective method for preventing influenza, and adjuvants can enhance the immune response intensity and persistence of influenza vaccines. However, there are currently shortcomings in clinical adjuvant approvals, ineffectiveness against weak antigens, and a tendency to cause headaches. Therefore, the development of safe and effective novel adjuvants for influenza vaccines is particularly important to enhance vaccine immunogenicity and safety. Given the wide range of sources, high safety, and biodegradability of traditional Chinese medicine(TCM), some studies have described it as a vaccine adjuvant. This article reviewed the current status and challenges of influenza vaccine adjuvants, summarized the types of TCM adjuvants, the safety and immunomodulatory effects of natural active ingredients from TCM combined with influenza vaccines, the role of TCM adjuvants in antigen storage, antigen presentation capability, immune cells and cytokines, and immune responses, and analyzed the advantages and disadvantages of TCM adjuvants compared with small molecule adjuvants, with the aim of promoting the clinical development and commercialization of TCM adjuvants for influenza vaccines.

Analysing the Potency of a Seasonal Influenza Vaccine Using Reference Antisera from Heterologous Strains.

The potency of inactivated seasonal influenza vaccine is harmonised by establishing the haemagglutinin (HA) content using the compendial single radial diffusion (SRD) method. SRD reagents (antigens and antisera) are prepared, calibrated and distributed by regulatory agencies as standards for potency testing, following the biannual World Health Organization (WHO) announcements of the virus strains suitable for inclusion in the vaccine. The generation of a homologous hyperimmune sheep antiserum constrains the time to vaccine release. This study tests the application of heterologous antisera to determine the potency of influenza vaccine compared to that of a standard homologous antiserum. The results indicate that the selected heterologous sheep antisera directed to seasonal H1N1, H3N2 or B Victoria virus strains can be used to determine the accurate potency of inactivated seasonal influenza vaccines. Individually selected antisera could be useful for two to fourteen seasons. A limitation to the heterologous antiserum approach is the diversity of each individual serum, indicating that the empirical determination of a specific serum is required. This application has the potential to enable the earlier availability of a seasonal vaccine and reduce animal usage.