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

During the coronavirus disease 2019 (COVID-19) pandemic, scheduled vaccinations were postponed, mass vaccination programmes were suspended and opportunities for healthcare workers to administer vaccines ad hoc decreased. The aims of this systematic literature review were to determine the impact of the COVID-19 pandemic on vaccine confidence, intent and uptake in preexisting routine childhood or adult vaccination programmes, and to identify factors associated with changes in acceptance, intent and uptake of preexisting vaccines. Medline and Embase were searched for studies in Australia, Brazil, Canada, China, Japan, the USA, and European countries, published between 1 January 2021 and 4 August 2022. A complementary gray literature search was conducted between 11 and 13 October 2022, and supplemented with additional gray research in October 2023. In total, 54 citations were included in the review. Study design and geography were heterogeneous. The number of adults who received or intended to receive an influenza or pneumococcal vaccine was higher during the pandemic than in previous seasons (n = 28 studies). In addition, increased acceptance of adult vaccinations was observed during 2020-21 compared with 2019-20 (n = 12 studies). The rates of childhood vaccinations decreased during the COVID-19 pandemic across several countries (n = 11 studies). Factors associated with changes in intention to receive a vaccination, or uptake of influenza vaccine, included previous vaccination, older age, higher perceived risk of contracting COVID-19, anxiety regarding the pandemic and fear of contracting COVID-19. Acceptance and uptake of influenza and pneumococcal vaccines generally increased after onset of the COVID-19 pandemic.

Influenza virus infection poses a continual menace to public health. Here, we developed soluble trimeric HA ectodomain vaccines by establishing interprotomer disulfide bonds in the stem region, which effectively preserve the native antigenicity of stem epitopes. The stable trimeric H1 ectodomain proteins exhibited higher thermal stabilities in comparison with unmodified HAs and showed strong binding activities towards a panel of anti-stem cross-reactive antibodies that recognize either interprotomer or intraprotomer epitopes. Negative stain transmission electron microscopy (TEM) analysis revealed the stable trimer architecture of the interprotomer disulfide-stapled WA11#5, NC99#2, and FLD#1 proteins as well as the irregular aggregation of unmodified HA molecules. Immunizations of mice with those trimeric HA ectodomain vaccines formulated with incomplete Freund\'s adjuvant elicited significantly more potent cross-neutralizing antibody responses and offered broader immuno-protection against lethal infections with heterologous influenza strains compared to unmodified HA proteins. Additionally, the findings of our study indicate that elevated levels of HA stem-specific antibody responses correlate with strengthened cross-protections. Our design strategy has proven effective in trimerizing HA ectodomains derived from both influenza A and B viruses, thereby providing a valuable reference for designing future influenza HA immunogens.

UNASSIGNED: 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.
UNASSIGNED: 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.
UNASSIGNED: 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).
UNASSIGNED: 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.

BACKGROUND: Influenza vaccination may protect through the humoral immune response, cellular immune response, or possibly both. Immunity after vaccination can be mediated through antibodies that may be detected by the rise of serum hemagglutination inhibition (HAI) titers. Our objective was to investigate the proportion of protection against influenza mediated through antibodies by measuring the rise of HAI titer (indirect effect) compared to that induced through other immune mechanisms (direct effect) for influenza A and B.
METHODS: We analysed data from a cluster randomized trial conducted during the 2008-2009 season in which Canadian Hutterite children were vaccinated against influenza. We used inverse probability weighting to calculate the indirect and direct effect of vaccination against influenza A/H3N2 and influenza B/Brisbane using HAI titres and overall vaccine efficacy.
RESULTS: We included data on 617 children from 46 Hutterite colonies, aged between 3 and 15 years who were vaccinated with either inactivated trivalent influenza vaccine or hepatitis A vaccine. Vaccine efficacy was 63 % for influenza A (H3N2) and 28 % for influenza B. The hazard ratio for protection against influenza A/H3N2 due to an indirect effect of vaccination was 0.96 (95 % confidence interval (CI) of 0.00 to 2.89) while for the direct effect it was 0.38 (95 % CI of 0.00 to 5.47). The hazard ratio for influenza B indirect effect was 0.75 (95 % CI of 0.07 to 1) and for the direct effect 0.96 (95 % CI of 0.00 to 12.02). In contrast, repeating the analysis using microneutralization in a subgroup of 488 children revealed that the protective effect for vaccination for A/H3N2 was entirely mediated by antibodies but only for 13 % for influenza B.
CONCLUSIONS: Although vaccination provided higher protective effectiveness against influenza A than B, most of the influenza A vaccine efficacy likely occurred through antibodies other than what could be detected by HAI titres. In contrast, for influenza B, while the HAI titres appeared to mediate most of the vaccine effectiveness, this was not confirmed by microneutralization analysis.

BACKGROUND: 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.
METHODS: 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.
CONCLUSIONS: 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.

Vaccine immunogenicity and reactogenicity depend on recipient and vaccine characteristics. We hypothesized that healthy adults reporting higher reactogenicity from seasonal inactivated influenza vaccine (IIV) developed higher antibody titers compared with those reporting lower reactogenicity. We performed a secondary analysis of a randomized phase 1 trial of a trivalent IIV delivered by microneedle patch (MNP) or intramuscular (IM) injection. We created composite reactogenicity scores as exposure variables and used hemagglutination inhibition (HAI) titers as outcome variables. We used mixed-model analysis of variance to estimate geometric mean titers (GMTs) and titer fold change and modified Poisson generalized estimating equations to estimate risk ratios of seroprotection and seroconversion. Estimates of H3N2 GMTs were associated with the Systemic and Local scores among the IM group. Within the IM group, those with high reaction scores had lower baseline H3N2 GMTs and twice the titer fold change by day 28. Those with high Local scores had a greater probability of seroconversion. These results suggest that heightened reactogenicity to IM IIV is related to low baseline humoral immunity to an included antigen. Participants with greater reactogenicity developed greater titer fold change after 4 weeks, although the response magnitude was similar or lower compared with low-reactogenicity participants.

BACKGROUND: COVID-19 is an infectious disease caused by SARS-CoV-2. It is unclear whether influenza vaccination reduces the severity of disease symptoms. Previous studies have suggested a beneficial effect of influenza vaccination on the severity of COVID-19. The aim of this study was to evaluate the possible protective effect of the influenza vaccine on the occurrence of SARS-CoV-2 infection symptoms and prognosis in patients hospitalized with COVID-19.
METHODS: This was a retrospective cohort study of patients who tested positive for SARS-CoV-2, identified by quantitative real-time polymerase chain reaction. Chi-square tests, Kaplan-Meier analysis, and multivariate analysis were performed to assess the association between influenza vaccination and the presence of symptoms in hospitalized patients with COVID-19 and their outcome.
RESULTS: In this study, 1712 patients received positive laboratory tests for SARS-CoV-2; influenza vaccination was a protective factor against the presence of characteristic COVID-19 symptoms such as polypnea, anosmia, dysgeusia, and fever (p < 0.001). Influenza-vaccinated patients had fewer days of hospitalization (p = 0.029).
CONCLUSIONS: The findings of this study support that influenza vaccination is associated with a decrease in the number of symptoms in patients hospitalized due to COVID-19, with fewer days of hospitalization, but not with the outcome of disease.

Notwithstanding prevalence gaps in micronutrients supporting immune functions, the significance of their deficits/supplementation for the efficacy of vaccines is underinvestigated. Thus, the influence of supplementation combining vitamins C and D, zinc, selenium, manganese, and N-acetyl cysteine on immune correlates/surrogates of protection conferred by a quadrivalent influenza vaccine (QIV) in mice was investigated. The supplementation starting 5 days before the first of two QIV injections given 28 days apart increased the serum titres of total and neutralizing IgG against each of four influenza strains from QIV. Accordingly, the frequencies of germinal center B cells, follicular CD4+ T helper (Th) cells, and IL-21-producing Th cells increased in secondary lymphoid organs (SLOs). Additionally, the supplementation improved already increased IgG response to the second QIV injection by augmenting not only neutralizing antibody production, but also IgG2a response, which is important for virus clearance, through favoring Th1 differentiation as indicated by Th1 (IFN-γ)/Th2 (IL-4) signature cytokine level ratio upon QIV restimulation in SLO cell cultures. This most likely partly reflected antioxidant action of the supplement as indicated by splenic redox status analyses. Thus, the study provides a solid scientific background for further research aimed at repurposing the use of this safe and inexpensive micronutrient combination to improve response to the influenza vaccine.

The influenza vaccine is one of the most commonly administered vaccines worldwide, with a high safety profile. However, rare cases of serious adverse events have been reported in the literature. We report a 77-year-old male who presented with progressive weakness in the lower extremities shortly after receiving the Influenza vaccine. He was diagnosed with myositis involving the paraspinal and bilateral lower extremity muscles. He received treatment with high-dose steroids and taper with full recovery of his muscle weakness. Although the exact causal mechanism between the vaccine and the patient\'s myositis could not be established, surveillance for such rare adverse events can provide data for future vaccine safety improvement. Due to well-known benefits of the Influenza vaccine that far exceed the potential adverse effects, we strongly encourage the readers to continue their vaccine practices as per CDC guidelines.