Caregiver's intention and uptake of influenza vaccination for children in Australia before and after introduction of free vaccination.

OBJECTIVES: To investigate the change between 2017 and 2023 in caregiver-reported intention to vaccinate children aged 6 months-5 years against influenza and compare this to vaccine uptake in Australia, following the COVID-19 pandemic and the free influenza vaccine policy for young children by different states and territories since 2018 and nationally in 2020. STUDY DESIGN: Retrospective data analysis. METHODS: A retrospective data analysis was conducted using the Royal Children's Hospital National Child Health Poll data. The data were collected through online cross-sectional surveys of Australian caregivers' intention to vaccinate their children against influenza in 2017 and 2023. The proportion of parents who intended to vaccinate their children against influenza was weighted to reflect Australia's population distribution. We compared this to National Centre for Immunisation Research Surveillance (NCIRS) data on the percentage (%) of children registered as actually having had the influenza vaccine in 2017 and 2023. RESULTS: In children aged five years and under, an increase in intention to vaccinate of 34.7 percentage points from 27.4% (weighted, n = 307/1050) in 2017 to 62.1% (weighted, n = 457/743) in 2023 was observed. We compared intention with the NCIRS influenza vaccine uptake data, which recorded an increased uptake for children under five years of 23.3 percentage points from 6.2% in 2017 to 28.2% in 2023. CONCLUSIONS: Between 2017 and 2023, there was a substantial increase in caregiver intention to vaccinate children against influenza, during which the national free influenza vaccine policy for young children was enacted and the COVID-19 pandemic began. There is a substantial gap between the intention to vaccinate and actual uptake of influenza vaccination, warranting further investigation into the barriers behind vaccination, beyond that of cost.

Real-world effectiveness of influenza vaccine over a decade during the 2011-2021 seasons-Implications of vaccine mismatch.

BACKGROUND: Influenza imposes a significant healthcare burden in Korea, leading the government to initiate a national immunization program. Previous studies on vaccine effectiveness (VE) were limited to single-season estimation in Korea. METHODS: This multicenter prospective cohort study enrolled patients with influenza-like illnesses at 10 medical centers in Korea from 2011 to 2021. The demographic and clinical data were collected from questionnaire surveys and electronic medical records. Using a test-negative design, we aimed to investigate the effectiveness of a seasonal influenza vaccine for antigenic matching of the vaccine and circulating viral strains over 10 seasons. RESULTS: Overall, 5322 adults aged ≥65 years were enrolled. Only three (33.3 %) of nine seasons showed >70 % antigenic match between vaccine and circulating strains. Influenza VE was significantly variable by season, ranging from -46.9 % (95 %confidence interval [CI]: -127.6-5.2) in the 2011/12 season to 47.7 % (95 %CI: 22.6-64.7) in the 2016/17 season. A significant difference was observed in the VE depending on whether the vaccine strains matched with epidemic strains: 28.8 % (95 %CI: 8.8-44.8) in matched seasons versus -12.0 % (95 %CI: -30.0-3.7) in mismatched seasons. Across the study period, influenza-related hospitalizations were reduced by 13.6 % (95 %CI: 0.7-24.8) with vaccination. In a subgroup analysis, the VE against influenza-related hospitalization was 48.4 % (95 %CI 29.6-62.2) in A/H3N2 dominant seasons and 53.8 % (95 %CI: -73.4-87.7) in A/H1N1 dominant seasons, respectively. CONCLUSION: Influenza vaccine mismatch was frequent over the study period, leading to negligibly low VE in mismatched seasons. Influenza vaccination reduces the risk of influenza-related hospitalizations.

Immunogenicity and safety of different combinations involving a third booster dose of SARS-CoV-2 inactivated vaccine, inactivated quadrivalent influenza vaccine, and 23-valent pneumococcal polysaccharide vaccine in adults aged ≥60 years: a phase 4, randomized, open-label study.

Background: Concomitant administration of COVID-19, influenza, and pneumococcal vaccines could reduce the burden on healthcare systems. However, the immunogenicity and safety of various combinations of a third booster dose of SARS-CoV-2 inactivated vaccine (CoronaVac), inactivated quadrivalent influenza vaccine (IIV4), and 23-valent pneumococcal polysaccharide vaccine (PPV23), particularly in different age groups, is still unknown. Methods: A phase 4, randomized, open-label, controlled trial was conducted in Beijing, China. 636 healthy adults were divided into two age groups (18-59 and ≥60 years) and randomized equally into three groups: CoronaVac and IIV4 followed by PPV23; CoronaVac and PPV23 followed by IIV4; or CoronaVac followed by IIV4 and PPV23, with a 28-day interval between vaccinations. Immunogenicity was evaluated by measuring antibody titers, and safety was monitored. ClinicalTrials.gov Identifier: NCT05298800. Results: Co-administration of a third dose of CoronaVac, IIV4, and PPV23 in any combination was safe. Among adults aged 18-59, co-administration with PPV23 maintained non-inferiority of antibody levels for CoronaVac and IIV4, despite a slight reduction in antibody responses. This reduction was not observed in participants ≥60 years. Furthermore, co-administration of IIV4 and PPV23 affected seroconversion rates for both vaccines. Conclusions: Co-administration of the third dose of SARS-CoV-2 inactivated vaccine with the influenza vaccine, followed by PPV23, may be optimal for adults aged 18-59. In adults ≥60, all vaccine combinations were immunogenic, suggesting a flexible vaccination approach. Since antibody measurements were taken 28 days post-vaccination, ongoing surveillance is essential to assess the longevity of the immune responses.

Adult indication 13-valent pneumococcal conjugate vaccine clinical development overview: formulation, safety, immunogenicity (dosing and sequence), coadministration, and efficacy.

INTRODUCTION: There was no 13-valent pneumococcal conjugate vaccine (PCV13) adult antibody concentration threshold regulatory criterion for licensure - unlike the pediatric indication; consequently, for the adult indication, PCV13 serotype-specific opsonophagocytic activity (OPA) geometric mean titer (GMT) values were immunobridged to the 23-valent plain polysaccharide vaccine (PPV23) to infer efficacy against invasive pneumococcal disease (IPD). Subsequently, a double-blind, randomized, controlled PCV13 efficacy trial (CAPiTA) was performed in community-living, older adults to confirm efficacy against vaccine-serotype IPD (VT-IPD) and establish efficacy against vaccine-serotype pneumococcal community-acquired pneumonia (VT-CAP). AREAS COVERED: This article summarizes 31 publications from the PCV13 adult indication clinical development trials and other PCV13 clinical studies, organized by formulation, reactogenicity and safety, immunogenicity, coadministration, and clinical efficacy. EXPERT OPINION: PCV13 had a favorable safety profile with an OPA response generally greater than PPV23 irrespective of age and of previous pneumococcal vaccination. PCV13 primed for enhanced immune responses with subsequent PCV13 or PPV23 dosing. Conversely, PPV23 was shown to blunt the response to subsequent PCV13. CAPiTA demonstrated PCV13 efficacy for at least five years against both VT-IPD and VT-CAP. The PCV13 clinical development program provided fundamental insights into this vaccine's adult-specific immune responses and confirmed the advantages of conjugate over plain polysaccharide technology.

Cost-effectiveness and public health impact of using high dose quadrivalent influenza vaccine in the French older adults population.

BACKGROUND: Seasonal influenza outbreaks in France cause a surge in patients, exacerbating the overburdened healthcare system each winter. Older adults are particularly vulnerable to serious events related to influenza. Quadrivalent influenza high dose (QIV HD) vaccines have been developed to offer better clinical protection in older adults, who often exhibit suboptimal immune response to quadrivalent influenza standard dose vaccines (QIV SD). This study aims to evaluate the public health impact and cost-effectiveness of administering HD versus SD vaccines to individuals aged 65+ in France. METHODOLOGY: Using a static model and decision-tree approach, the study analyzed health outcomes such as influenza cases, GP (general practitioner) visits, hospitalizations, and mortality; relative vaccine efficacy (rVE) estimates were derived from a pivotal randomized-controlled trial and a meta-analysis comparing HD to SD vaccines. Two approaches were implemented to model hospitalizations (conditional on influenza or not), and analyses on bed occupancy were performed. RESULTS: Results showed that using QIV HD instead of QIV SD during an average influenza season in France led to the prevention of 57,209 additional cases of influenza, 13,704 GP visits, and 764 influenza-related deaths. Moreover, switching to QIV HD resulted in an additional 1,728-15,970 hospitalizations avoided and 15,124-138,367 reduced days of hospitalization depending on the hospitalization approach used. The cost-utility analysis showed a cost per quality-adjusted life year (QALY) gained ranging from 24,020 €/QALY to 5,036 €/QALY. CONCLUSIONS: Switching to QIV HD in older adults was shown to be cost-effective, with even greater public health benefits at a higher coverage rate, regardless of the season severity.

Influenza Epidemiology and Vaccine Effectiveness Following Funded Influenza Vaccine in Queensland, Australia, 2022.

BACKGROUND: In 2022, publicly funded influenza vaccine was made available to all residents of Queensland, Australia. This study compared influenza epidemiology in 2022 with previous years (2017-2021) and estimated influenza vaccine effectiveness (VE) during 2022. METHODS: The study involved a descriptive analysis of influenza notifications and a case-control study to estimate VE. Cases were notifications of laboratory-confirmed influenza, and controls were individuals who were test negative for COVID-19. Cases and controls were matched on age, postcode and specimen collection date. VE against hospitalisation was investigated by matching hospitalised cases to controls. Conditional logistic regression models were adjusted for sex. RESULTS: In 2022, Queensland experienced an early influenza season onset (April-May) and high case numbers (n = 45,311), compared to the previous 5 years (annual average: 29,364) and 2020-2021 (2020:6047; 2021:301) during the COVID-19 pandemic. Adjusted VE (VEadj) against laboratory-confirmed influenza was 39% (95% confidence interval [CI]: 37-41), highest for children aged 30 months to < 5 years (61%, 95% CI: 49-70) and lowest for adults aged ≥ 65 years (24%, 95% CI: 17-30). VEadj against influenza-associated hospitalisation was 54% (95% CI: 48-59). Among children < 9 years of age, VEadj against laboratory-confirmed influenza (55%, 95% CI: 49-61) and hospitalisation (67%, 95% CI: 39-82) was higher in those who received a complete dose schedule. CONCLUSION: In Queensland, the 2022 influenza season started earlier than the previous 5 years. VE against influenza notifications varied across age groups. VE estimates against influenza-associated hospitalisation were higher than those against laboratory-confirmed influenza.

Epidermal Growth Factor Receptor Emerges as a Viable Target for Reducing Tumorigenicity of MDCK Cells.

The MDCK cell line is perceived as better than the embryos of hen eggs for the production of influenza vaccines, but the tumorigenicity of these cells is concerning. Epidermal growth factor receptor (EGFR) is likely to be a crucial target that contributes to the tumorigenicity of MDCK cells. In this study, EGFR-knockdown and EGFR-overexpression cell lines were established. EGFR's influence on cell growth, migration, clonogenic ability, and flu virus susceptibility was evaluated in vitro, and its role in cell tumorigenicity was examined in nude mice. GST pull-down coupled with mass spectrometry (MS) and bioinformatics analysis identified EGFR-interacting proteins. The expression levels of these proteins, as well as those of PI3K-AKT- and MAPK-ERK-signaling-pathway-related molecules, were confirmed at both gene and protein levels. The result indicates that EGFR overexpression can enhance cell proliferation, migration, and clonal formation; EGFR knockdown could effectively curtail tumorigenesis and amplify the titers of influenza viruses in MDCK cells. An analysis of the underlying mechanism identified a total of 21 interacting proteins implicated in tumor formation, and among these, AKT1, CDK4, GNB2, and MAPK8 were confirmed at both gene and protein levels. EGFR can activate key factors of the PI3K-AKT signaling pathway, AKT and PI3K, and promote their phosphorylation levels. Consequently, we concluded that EGFR interacts with GNB2, facilitating transmembrane signal transduction, activating the PI3K-AKT signaling cascade, controlling cell cycle alterations, stimulating cell proliferation, and promoting tumorigenesis.

Single-centre, randomised clinical trial of the immunomodulatory mechanisms of daily supplementation of palm tocotrienol-rich fraction in healthy human volunteers following influenza vaccination.

Background: Vitamin E from palm oil, known as the tocotrienol-rich fraction (TRF), has been shown to have immune-enhancing activity. To date, only one dose of TRF (400 mg daily) has been tested in a clinical trial. The proposed study will evaluate the immune-enhancing activity effects of lower doses (200, 100 and 50 mg) in a clinical trial using an influenza vaccine as the immunological challenge. Methods: A single-centre, randomised, parallel, double-blinded, placebo-controlled clinical trial with balance allocation involving five arms will be conducted. The healthy volunteers recruited will be randomly assigned to one of the arms, and they will be asked to take the respective supplements (400 mg, 200 mg, 100 mg, 50 mg of TRF or placebo) daily with their dinner. The volunteers will receive the influenza vaccine after four weeks. They will be asked to return to the study site four weeks later. A blood sample will be taken for the study at baseline, four and eight weeks. Primary outcome measures will be antibody levels to influenza, blood leucocyte profile and cytokine production. Secondary outcomes will be correlating plasma vitamin E levels with immune responses, plasma proteins and gene expression patterns. The findings from this study will be published in relevant peer-reviewed journals and presented at relevant national and international scientific meetings. Conclusions: The recent world events have created the awareness of having a healthy and functional immune system. Nutrition plays an important role in helping the immune system to function optimally. This study will show the effects of lower doses of TRF in boosting the immune response of healthy individuals and also elucidate the mechanisms through which TRF exerts its immune-enhancing effects. Clinical trial registration: Australian New Zealand Clinical Trials Registry (ANZCTR) [ ACTRN12622000844741] dated 15 June 2022. Protocol version: 2.

Protection against influenza hospitalizations from enhanced influenza vaccines among older adults: A systematic review and network meta-analysis.

BACKGROUND: Influenza vaccines are available to help protect persons aged ≥65 years, who experience thousands of influenza hospitalizations annually. Because some influenza vaccines may work better than others, we sought to assess benefit of high-dose (HD), adjuvanted (ADJ), and recombinant (RIV) influenza vaccines ("enhanced influenza vaccines") compared with standard-dose unadjuvanted influenza vaccines (SD) and with one another for prevention of influenza-associated hospitalizations among persons aged ≥65 years. METHODS: We searched MEDLINE, Embase, CINAHL, Scopus, and Cochrane Library to identify randomized or observational studies published between January 1990 and October 2023 and reporting relative vaccine effectiveness (rVE) of HD, ADJ, or RIV for prevention of influenza-associated hospitalizations among adults aged ≥65 years. We extracted study data, assessed risk of bias, and conducted random-effects network meta-analysis and meta-regression. RESULTS: We identified 32 studies with 90 rVE estimates from five randomized and 27 observational studies (71,459,918 vaccinated participants). rVE estimates varied across studies and influenza seasons. Pooled rVE from randomized studies was 20% (95% CI -54 to 59) and 25% (95% CI -19 to 53) for ADJ and HD compared with SD, respectively; rVE was 6% (95% CI -109 to 58) for HD compared with ADJ; these differences were not statistically significant. In observational studies, ADJ, HD, and RIV conferred modestly increased protection compared with SD (rVE ranging from 10% to 19%), with no significant differences between HD, ADJ, and RIV. With enhanced vaccines combined, rVE versus SD was 18% (95% CI 3 to 32) from randomized and 11% (95% CI 8 to 14) from observational evidence. Meta-regression of observational studies suggested that those requiring laboratory confirmation of influenza reported greater benefit of enhanced vaccines. CONCLUSIONS: HD, ADJ, and RIV provided stronger protection than SD against influenza hospitalizations among older adults. No differences in benefit were observed in comparisons of enhanced influenza vaccines with one another.

Polymyositis and Severe Rhabdomyolysis in the Context of Influenza and COVID-19 Vaccination: A Case Report.

Rhabdomyolysis is characterized by muscle breakdown and the release of muscle enzymes into the bloodstream, which can lead to acute kidney injury (AKI) and electrolyte imbalances. This case report details a 52-year-old male who developed severe rhabdomyolysis and polymyositis following influenza and SARS-COV-2 vaccinations. Presenting with severe muscle pain and elevated creatine kinase (CK) levels, the patient's condition was managed with aggressive hydration and supportive care, resulting in significant recovery. While vaccine-related adverse effects such as myositis and rhabdomyolysis are rare, this case underscores the need for vigilance in monitoring post-vaccination complications and highlights the importance of recognizing and promptly treating vaccine-associated inflammatory myopathies to prevent severe complications. The findings contribute to the growing body of literature on vaccine-induced myopathies and emphasize the necessity of a multidisciplinary approach in managing such complex cases.

Maternal influenza vaccination and associated risk of fetal loss: A claims-based prospective cohort study.

BACKGROUND: Although numerous studies support the safety of influenza vaccination during pregnancy, fewer studies have evaluated the risk of miscarriage or considered the effect of prior immunization. METHODS: Using national de-identified administrative claims data from the Optum Labs Data Warehouse, we conducted a claims-based cohort study of 117,626 pregnancies between January 2009 and December 2018. We identified pandemic A(H1N1)pdm09 and seasonal influenza vaccinations using CPT codes. Fetal loss was defined as miscarriage, medical termination, or stillbirth as identified by ICD-10-CM diagnostic codes. Cox proportional hazard models treating influenza vaccination as a time-varying exposure, weighted for loss-to-follow-up and stratified by baseline probability of vaccination, were used to model the risk of fetal loss by exposure to influenza vaccine. RESULTS: About 31.4 % of the cohort had a record of influenza vaccination; 10.0 % were vaccinated before pregnancy only, 17.8 % during pregnancy only, and 3.6 % before and during pregnancy. The risk of miscarriage was 39 % lower among those vaccinated during pregnancy compared to unvaccinated (adjusted hazard ratio, aHR 0.61; 95 % CI 0.50, 0.74) and was similar for medical termination or stillbirth (HR 0.69; 95 % CI 0.45, 1.03 and aHR 0.99; 95 % CI 0.76, 1.30, respectively). Similar results were observed for women who received the vaccine before and during pregnancy. We observed little to no association between vaccination before pregnancy and risk of miscarriage (HR 0.98; 95 % CI 0.76, 1.26), medical termination (HR 1.02; 95 % CI 0.46, 2.24), or stillbirth (HR 1.14, 95 % CI 0.77, 1.69). DISCUSSION: Influenza vaccination was not associated with an increased risk of fetal loss. These results support the safety of influenza vaccine administration even when administered before or early during pregnancy.

Syncope after live attenuated influenza vaccine: Reports to the Vaccine Adverse Event Reporting System (2003-2024).

Vasovagal syncope, or fainting, can be triggered by various stimuli, including medical procedures. Syncope after vaccination has been reported, most commonly among adolescents, and can result in injuries. Using the Vaccine Adverse Event Reporting System (VAERS), we reviewed and summarized reports of syncope after live attenuated influenza vaccine, intranasal (LAIV) administered as the sole vaccine (i.e., no concomitant injections). From June 17, 2003 (date of LAIV licensure in the US) through May 31, 2024, VAERS received 50 reports of syncope after LAIV. Nearly half (23; 46 %) pertained to individuals 10-19 years of age. While the vast majority of reports (35; 70 %) did not describe any injuries, 15 people (30 %) were injured, most commonly by falling and hitting their head or face. Twenty-two people (44 %) required evaluation in the emergency department or doctor's office, including an individual who lost consciousness while he was driving home from the vaccination appointment. He did not report any injuries, but the car was severely damaged. Nearly three-quarters of people (37; 74 %) developed syncope within 15 min after vaccination, but fewer than half of reports (24; 48 %) stated that the patient had waited in the observation area for at 15 min. Based on approximately 111.9 million doses of LAIV distributed in the US during the same time period, the reporting rate is approximately 0.4 per million doses, suggesting that syncope following LAIV is rare. The information summarized here may enable clinicians, patients, and caregivers to make a more informed decision regarding preventing injuries that may occur following LAIV-related syncope.

The impact of attitude toward COVID-19 vaccine on intention to receive influenza vaccination: a multi-group comparison based on the influence of presumed influence model and spillover effects.

Introduction: Influenza vaccination is one of the most important strategies for preventing influenza. However, the influenza vaccination rate in China remains low. During the COVID-19 pandemic, people held different attitudes toward the COVID-19 vaccine. In the post-pandemic era, do the varying attitudes toward the COVID-19 vaccine affect the intention to receive influenza vaccination? Methods: Based on the influence of presumed influence (IPI) model and spillover effects, this study employed structural equation modeling for multi-group comparison to analyze questionnaires from 613 participants, using instruments such as the Perceived Media Influence on Others Scale (PMIO), the Susceptibility to Influenza Scale (SI), and the Attitude toward Influenza Vaccine Scale (AIV). Results: The key findings are as follows: (1) Information exposure to the influenza vaccine significantly influences perceived media influence on others. (2) Perceived media influence on others does not directly impact the intention to receive influenza vaccination but rather affects it through attitude toward the influenza vaccine. (3) Moreover, multi-group analyses revealed differences in the IPI model among audiences with different attitudes toward the COVID-19 vaccine. These differences demonstrated that prior attitudes toward the COVID-19 vaccine can influence attitudes toward similar influenza vaccines, thus demonstrating the existence of spillover effects. Conclusion: Attitude toward the COVID-19 vaccine can influence the intention to receive the influenza vaccination. Those with a negative attitude toward the COVID-19 vaccine are significantly influenced by susceptibility to influenza. Perceived media influence affects the intention to receive the influenza vaccination among those with a positive attitude toward the COVID-19 vaccine.

A cross-sectional study on the understanding and attitudes toward influenza and influenza vaccines among different occupational groups in China.

This study aimed to assess the level of knowledge regarding influenza viruses and vaccines among different professional groups to investigate the reasons for vaccine hesitancy. We collected 2190 questionnaires regarding influenza vaccines in China in 2022. The respondents were categorized into the general population (GP), foreign affairs workforce population (FAWP), and veterinary workforce population (VWP) according to their job positions. Linear regression was used to assess the association between multiple factors and influenza vaccination rates. The association between work and influenza vaccination rates was also assessed by grouping different workforce populations. The vaccination rate of the GP was higher than that of the VWP (odds ratio: 1.342, 95% confidence interval: 1.025-1.853), surpassing the rates reported in previous studies. This may be attributed to heightened concerns about infectious diseases influenced by the ongoing coronavirus disease 2019 pandemic. Despite the VWP's more in-depth knowledge of the VWP on zoonotic diseases and their recognition of their importance, there was no significant difference in influenza knowledge among the three populations. This discrepancy contrasts with the observed differences in vaccination rates. Further investigation revealed that, compared with FAWP, the price of vaccines emerged as a primary influencing factor for vaccination rates (odds ratio:0.398, 95%CI; 0.280-0.564). General concerns regarding the protective effects and side effects of vaccines were also noted.

Differential effects of social versus monetary incentives on inhibitory control under acute inflammation.

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 (Nobs = 30,528). For no-go trials, we did not find significant associations between IL and 6 reactivity between the sessions and changes in trial accuracy. For go trials, we found significant differences in the associations between IL and 6 reactivity and changes in accuracy from session 1 to session 2 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 picture) 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.

A Single-Component Multilayered Self-Assembling Protein Nanoparticle Vaccine Based on Extracellular Domains of Matrix Protein 2 against Both Influenza A and B.

The development of an effective and broadly protective influenza vaccine against circulating and emerging strains remains elusive. In this study, we evaluated a potentially universal influenza vaccine based on single-component self-assembling protein nanoparticles (1c-SApNPs) presenting the conserved matrix protein 2 ectodomain (M2e) from influenza A and B viruses (IAV and IBV, respectively). We previously designed a tandem antigen comprising three IAV M2e domains of human, avian/swine, and human/swine origins (termed M2ex3). The M2ex3-presenting 1c-SApNPs conferred complete protection in mice against sequential lethal challenges with H1N1 and H3N2. To broaden this protection to cover IBVs, we designed a series of antigens incorporating different arrangements of three IAV M2e domains and three copies of IBV M2e. Tandem repeats of IAV and IBV (termed influenza A-B) M2e arrayed on the I3-01v9a 60-mer 1c-SApNP, when formulated with an oil-in-water emulsion adjuvant, generated greater M2e-specific immunogenicity and protective efficacy than the soluble influenza A-B M2e trimer, indicated by higher survival rates and reduced weight loss post-challenge. Importantly, one of the influenza A-B M2e SApNP constructs elicited 100% protection against a lethal influenza A/Puerto Rico/8/1934 (H1N1) challenge in mice and 70% protection against a lethal influenza B/Florida/4/2006 (Yamagata lineage) challenge, the latter of which has not been reported in the literature to date. Our study thus provides a promising M2e-based single-component universal vaccine candidate against the two major types of influenza virus circulating in humans.

Phase I Clinical Study of the Subunit Betulin-Adjuvanted Tetravalent Candidate Influenza Vaccine TetraFluBet.

OBJECTIVES: This study aimed to determine the safety, tolerability and immunogenicity of TetraFluBet, an inactivated subunit influenza vaccine that contains a corpuscular immuno-adjuvant derived from natural betulin. METHODS: We conducted a prospective, randomized, open-labeled, single-center, phase I trial. The study was conducted in two stages: 5 volunteers in stage I and 25 volunteers in stage II. Eligible participants received one single dose (20 µg/0.5 mL) of TetraFluBet intramuscularly. Participants were followed for adverse events and reactogenicity. Seroconversion rate, seroprotection level, geometric mean titers (GMTs) of virus-neutralizing antibodies, IFN-γ induction and cell-mediated immunity were assessed. RESULTS: A total of 30 participants were enrolled. No vaccine-related serious adverse events were observed. The proportions of study participants with 4-fold seroconversions assessed by the HI assay (with 95% CIs) were 80.0% (62.7; 90.5), 70.0% (52.1; 83.3), 63.3% (45.5; 78.1) and 73.3% (55.6; 85.8) for influenza virus subtypes A (H1N1), A (H3N2), B1 and B2, respectively. Seroprotection levels (with 95% CIs) were 83.3% (66.4; 92.7), 83.3% (66.4; 92.7), 73.3% (55.6; 85.8) and 66.7% (48.8; 80.8), respectively. The fold increases in the GMTs of virus-neutralizing antibodies for subtype H1N1 was 6.50, for subtype H3N2 was 3.03, for subtype B1 was 3.56 and for subtype B2 was 6.07. The population of cytotoxic T-cells increased significantly in the post-vaccination period, indicating a strong CD3+CD8+ response. CONCLUSIONS: TetraFluBet tetravalent inactivated subunit vaccine with adjuvant demonstrated pronounced immunogenic properties, leading to the formation of both specific humoral and cellular immunity at a 20 µg dose.

Safety and Immunogenicity of a Carbohydrate Fatty Acid Monosulphate Ester Adjuvant Combined with a Low-Dose Quadrivalent Split-Virion Inactivated Influenza Vaccine: A Randomised, Observer-Blind, Active-Controlled, First-in-Human, Phase 1 Study.

Seasonal influenza vaccine effectiveness is low. Carbohydrate fatty acid monosulphate ester (CMS), a new oil-in-water adjuvant, has proven potency in animal models with suggested capacity for dose-sparing. The objective was to evaluate safety and immunogenicity of CMS when added to a low-dose influenza vaccine (QIV) in humans. In a randomised, double-blind, active-controlled, first-in-human study, sixty participants (18-50 years) received either 0.5 mg CMS or 2 mg CMS with 1/5th dose QIV, or a full dose QIV without CMS. Adverse events (AE) were monitored until 7 days post-vaccination. Haemagglutinin inhibition (HI) titres in serum and CD4+ T cells in PBMCs were determined at day 0, 7, 28, and 180. Mean age was 37.6 (±10.1) years and 42/60 (70.0%) were female. Pain at injection site (42/60, 86.7%) and headache (34/60, 56.7%) were reported most and more frequently in the 2 mg CMS group. HI titres and the frequency of influenza specific CD4+ T cells were equal across strains for the three cohorts on all visits, increased until day 28 and decreased at day 180 to values higher than baseline. CMS was safe in humans. Humoral and cell-mediated immunogenicity was similar across vaccines, even with 1/5th antigen dose. CMS can have beneficial implications in low-resource settings or in a pandemic context.

Analysis of factors influencing influenza outbreaks in schools in Taicang City, China.

Objective: This study aims to analyze the awareness of influenza prevention and control and the behavioral attitudes toward the work among parents and staff in schools in Taicang City and the impact of the vaccination rate among students on influenza outbreaks in schools. The findings can provide references for the development of effective control strategies for the spread of influenza. Methods: An anonymous questionnaire survey was conducted on 10,962 students from 20 schools in Taicang City, with class as the unit of analysis. The survey investigated their awareness of influenza prevention and control, their attitudes, and the vaccination coverage. Results: From January to June 2023, a total of 388 influenza outbreaks were reported in schools in Taicang City, involving 77 schools. There were 3,475 confirmed cases, with an average infection rate of 18.53%. In schools where influenza outbreaks had occurred, the incidence rate of those who received influenza vaccine was significantly lower than those who did not, and the vaccine protection rate was 28.22%. The knowledge awareness rates of "the main transmission routes of influenza" and "influenza vaccination can prevent influenza" among parents of students were 95.49 and 93.16%, respectively. The differences between schools involved in the epidemic and non-epidemic were statistically significant (p < 0.05). The correct attitudes of parents toward "actively reporting relevant symptoms to teachers when their children show symptoms" and "avoiding classes with diseases when their children are suspected to be sick" are 98.80 and 96.26%, respectively. The differences between schools with and without epidemic are statistically significant (p < 0.05). The correct attitudes of the class teacher toward "correct management and control of students with flu like symptoms in the class" and "taking correct prevention and control measures in the event of a flu epidemic in the class" were 89.36 and 92.55%, respectively. The differences between epidemic related and non-epidemic related classes were statistically significant (p < 0.05). Conclusion: Enhance the knowledge level of influenza prevention and control among parents of students, Strengthening the training for class teachers in emergency response to infectious diseases and increasing vaccination coverage among students can effectively reduce the incidence of influenza and thereby the occurrence of cluster outbreaks in schools.