Changes in the urinary proteome before and after quadrivalent influenza vaccine and COVID-19 vaccination.

The proteome of urine samples from quadrivalent influenza vaccine cohort were analyzed with self-contrasted method. Significantly changed urine protein at 24 hours after vaccination was enriched in immune-related pathways, although each person's specific pathways varied. We speculate that this may be because different people have different immunological backgrounds associated with influenza. Then, urine samples were collected from several uninfected SARS-CoV-2 young people before and after the first, second, and third doses of the COVID-19 vaccine. The differential proteins compared between after the second dose (24h) and before the second dose were enriched in pathways involving in multicellular organismal process, regulated exocytosis and immune-related pathways, indicating no first exposure to antigen. Surprisingly, the pathways enriched by the differential urinary protein before and after the first dose were similar to those before and after the second dose. It is inferred that although the volunteers were not infected with SARS-CoV-2, they might have been exposed to other coimmunogenic coronaviruses. Two to four hours after the third vaccination, the differentially expressed protein were also enriched in multicellular organismal process, regulated exocytosis and immune-related pathways, indicating that the immune response has been triggered in a short time after vaccination. Multicellular organismal process and regulated exocytosis after vaccination may be a new indicator to evaluate the immune effect of vaccines. Urinary proteome is a terrific window to monitor the changes in human immune function.

Healthcare professionals' beliefs regarding influenza vaccination: What has COVID-19 changed?

Background: Influenza poses a potential public health threat among healthcare professionals since an infected healthcare professional can spread the virus to patients at higher risk as well as his/her own family members and colleagues. Annual influenza vaccination is the most effective way to protect HCPs. Aim: This study was conducted to determine whether demand for and beliefs about influenza vaccination have changed among healthcare professionals in the COVID-19 era and the factors that might have influenced them in the early phase of the pandemic when COVID-19 vaccines were eagerly awaited. Patients and Methods: This observational descriptive study was conducted between November 16, and December 15, 2020. A total of 317 healthcare professionals completed an online survey. Bivariate analysis and binary logistic regression analysis were performed. Results: Nineteen (6.0%) healthcare professionals were regularly vaccinated against influenza every year, and 199 (62.8%) had never been vaccinated. During the 2019-2020 season, 30 (9.5%) participants had been vaccinated and the proportion desiring to be vaccinated against influenza during the 2020-2021 season was 49.8% (n = 158). The results revealed that those with chronic diseases, those who believed they had adequate information about influenza vaccination and those who believed healthcare professionals should be vaccinated against influenza regularly every year, respectively, had 3.5 times, 4.7 times, and 11 times higher vaccination rates. Conclusion: Although the proportion of healthcare professionals with the intention to be vaccinated for influenza increased with the COVID-19 pandemic, it is still not high enough. Influenza vaccination rates should be promoted by in-service training programs.

Comparing the Use of a Mobile App and a Web-Based Notification Platform for Surveillance of Adverse Events Following Influenza Immunization: Randomized Controlled Trial.

BACKGROUND: Vaccine safety surveillance is a core component of vaccine pharmacovigilance. In Canada, active, participant-centered vaccine surveillance is available for influenza vaccines and has been used for COVID-19 vaccines. OBJECTIVE: The objective of this study is to evaluate the effectiveness and feasibility of using a mobile app for reporting participant-centered seasonal influenza adverse events following immunization (AEFIs) compared to a web-based notification system. METHODS: Participants were randomized to influenza vaccine safety reporting via a mobile app or a web-based notification platform. All participants were invited to complete a user experience survey. RESULTS: Among the 2408 randomized participants, 1319 (54%) completed their safety survey 1 week after vaccination, with a higher completion rate among the web-based notification platform users (767/1196, 64%) than among mobile app users (552/1212, 45%; P<.001). Ease-of-use ratings were high for the web-based notification platform users (99% strongly agree or agree) and 88.8% of them strongly agreed or agreed that the system made reporting AEFIs easier. Web-based notification platform users supported the statement that a web-based notification-only approach would make it easier for public health professionals to detect vaccine safety signals (91.4%, agreed or strongly agreed). CONCLUSIONS: Participants in this study were significantly more likely to respond to a web-based safety survey rather than within a mobile app. These results suggest that mobile apps present an additional barrier for use compared to the web-based notification-only approach. TRIAL REGISTRATION: ClinicalTrials.gov NCT05794113; https://clinicaltrials.gov/show/NCT05794113.

Immune interference in effectiveness of influenza and COVID-19 vaccination.

Vaccines are known to function as the most effective interventional therapeutics for controlling infectious diseases, including polio, smallpox, rabies, tuberculosis, influenza and SARS-CoV-2. Smallpox has been eliminated completely and polio is almost extinct because of vaccines. Rabies vaccines and Bacille Calmette-Guérin (BCG) vaccines could effectively protect humans against respective infections. However, both influenza vaccines and COVID-19 vaccines are unable to eliminate these two infectious diseases of their highly variable antigenic sites in viral proteins. Vaccine effectiveness (VE) could be negatively influenced (i.e., interfered with) by immune imprinting of previous infections or vaccinations, and repeated vaccinations could interfere with VE against infections due to mismatch between vaccine strains and endemic viral strains. Moreover, VE could also be interfered with when more than one kind of vaccine is administrated concomitantly (i.e., co-administrated), suggesting that the VE could be modulated by the vaccine-induced immunity. In this review, we revisit the evidence that support the interfered VE result from immune imprinting or repeated vaccinations in influenza and COVID-19 vaccine, and the interference in co-administration of these two types of vaccines is also discussed. Regarding the development of next-generation COVID-19 vaccines, the researchers should focus on the induction of cross-reactive T-cell responses and naive B-cell responses to overcome negative effects from the immune system itself. The strategy of co-administrating influenza and COVID-19 vaccine needs to be considered more carefully and more clinical data is needed to verify this strategy to be safe and immunogenic.

Evaluation of missed influenza vaccination opportunities in the emergency department.

BACKGROUND: Seasonal influenza is associated with significant healthcare resource utilization. An estimated 490,000 hospitalizations and 34,000 deaths were attributed to influenza during the 2018-2019 season. Despite robust influenza vaccination programs in both the inpatient and outpatient setting, the emergency department (ED) represents a missed opportunity to vaccinate patients at high risk for influenza who do not have access to routine preventive care. Feasibility and implementation of ED-based influenza vaccination programs have been previously described but have stopped short of describing the predicted health resource impact. The goal of our study was to describe the potential impact of an influenza vaccination program in an urban adult emergency department population using historic patient data. METHODS: This was a retrospective study of all encounters within a tertiary care hospital-based ED and three freestanding EDs during influenza season (defined as October 1 - April 30) over a two-years, 2018-2020. Data was obtained from the electronic medical record (EPIC®). All ED encounters during the study period were screened for inclusion using ICD 10 codes. Patients with a confirmed positive influenza test and no documented influenza vaccine for the current season were reviewed for any ED encounter at least 14 days prior to the influenza-positive encounter and during the concurrent influenza season. These ED visits were deemed a missed opportunity to provide vaccination and potentially prevent the influenza-positive encounter. Healthcare resource utilization, including subsequent ED encounters and inpatient admissions, were evaluated for patients with a missed vaccination opportunity. RESULTS: A total of 116,140 ED encounters occurred during the study and were screened for inclusion. Of these, 2115 were influenza-positive encounters, which represented 1963 unique patients. There were 418 patients (21.3%) that had a missed opportunity to be vaccinated during an ED encounter at least 14 days prior to the influenza-positive encounter. Of those with a missed vaccination opportunity, 60 patients (14.4%) had subsequent influenza-related encounters, including 69 ED visits and 7 inpatient admissions. CONCLUSION: Patients presenting to the ED with influenza frequently had opportunities to be vaccinated during prior ED encounters. An ED-based influenza vaccination program could potentially reduce influenza-related burden on healthcare resources by preventing future influenza-related ED encounters and hospitalizations.

Immune Response to Seasonal Influenza Vaccination in Multiple Sclerosis Patients Receiving Cladribine.

Cladribine has been approved for the treatment of multiple sclerosis (MS) and its administration results in a long-lasting depletion of lymphocytes. As lymphopenia is known to hamper immune responses to vaccination, we evaluated the immunogenicity of the influenza vaccine in patients undergoing cladribine treatment at different stages vs. controls. The antibody response in 90 cladribine-treated MS patients was prospectively compared with 10 control subjects receiving platform immunotherapy (NCT05019248). Serum samples were collected before and six months after vaccination. Response to vaccination was determined by the hemagglutination-inhibition test. Postvaccination seroprotection rates against influenza A were comparable in cladribine-treated patients and controls (H1N1: 94.4% vs. 100%; H3N2: 92.2% vs. 90.0%). Influenza B response was lower in the cladribine cohort (61.1% vs. 80%). The increase in geometric mean titers was lower in the cladribine group vs. controls (H1N1: +98.5 vs. +188.1; H3N2: +225.3 vs. +300.0; influenza B: +40.0 vs. +78.4); however, titers increased in both groups for all strains. Seroprotection was achieved irrespective of vaccination timing and lymphocyte subset counts at the time of vaccination in the cladribine cohort. To conclude, cladribine-treated MS patients can mount an adequate immune response to influenza independently of treatment duration and time interval to the last cladribine administration.

Effect of COVID-19 vaccination on influenza-associated respiratory infection (IARI): benefit or backfire.

OBJECTIVE: Undoubtfully, COVID-19 vaccine (C19V) has significantly changed the pandemic's trajectory positively. At the same time, reports of transient local and systemic post-vaccination reactions leave a concern about its unknown impact on common ailments. Its effect on IARI is unclear because the present IARI epidemic began immediately after C19V in the previous season. PATIENTS AND METHODS: A retrospective observational cohort study among 250 Influenza-associated respiratory infection (IARI) patients by a structured interview questionnaire was conducted with the comparison between 3 groups with 1 dose, 2 doses and 2 doses plus booster dose of C19V. The p<0.05 was considered significant in this study. RESULTS: Among samples 21.2% received one dose of the C19V, only 3.6% got Flu vaccination, 30% had ≥2 comorbidities such as diabetes (22.8%), hypertension (28.4%) and ionically, 77.2% were on chronic medications. Significant differences (p<0.05) were found between groups with duration of illness, cough, headache, fatigue, shortness of breath and hospital visits. The logistic regression analysis shows that the extended IARI symptoms and hospital visits were significantly high among Group 3 (OR=9.17, 95% CI=3.01-29.0) and the same trend remained significant after adjusting the incidence of comorbidities among samples, the chronic conditions (OR=5.13, 95% CI=1.37-14.91) and flu vaccination status (O=4.96, 95% CI=1.41-16.2). Also, 66.4% of the patients were indecisive about getting vaccinated further. CONCLUSIONS: It has been challenging to reach any definitive conclusions regarding the effects of C19V on IARI, conducting extensive, substantial population-based studies that integrate clinical and virological data from more than one season is absolutely required, despite the fact that the majority of the reported effects were mild and temporary.

Analysis of COVID-19 mRNA Vaccine-induced Mouth Ulcers Using the Japanese Adverse Drug Event Report Database.

There are case reports of mouth ulcers caused by the coronavirus disease 2019 (COVID-19) messenger ribonucleic acid (mRNA) vaccine; however, the actual number and characteristics of cases are unknown. Therefore, we examined this issue using the Japanese Adverse Drug Event Report (JADER), a large Japanese database. We calculated the reported odds ratio (ROR) of drugs that may be specifically associated with mouth ulcers and assumed that a signal was present if the lower limit of the calculated ROR's 95% confidence interval (CI) was > 1. In addition, the time to symptom onset after administration of the COVID-19 mRNA and influenza HA vaccines was investigated. We found that the JADER database contained 4,661 mouth ulcer cases between April 2004 and March 2022. The COVID-19 mRNA vaccine was the eighth most common causative drug for mouth ulcers, with 204 reported cases. The ROR was 1.6 (95% CI, 1.4-1.9) and a signal was detected. There were 172 mouthulcer cases associated with the Pfizer-BioNTech's COVID-19 mRNA vaccine, 76.2% of which were female. The outcome was no unrecovered cases with the influenza HA vaccine, whereas the COVID-19 mRNA vaccine showed unrecovered cases (Pfizer-BioNTech: 12.2%, Moderna: 11.1%). The median time-to-onset of the mouth ulcers was two days for the COVID-19 mRNA vaccine and one day for the influenza HA vaccine, indicating that mouth ulcers caused by the COVID-19 mRNA vaccine were delayed adverse events. In this study, the COVID-19 mRNA vaccine was shown to cause mouth ulcers in a Japanese population.

Cellular immunity in COVID-19 and other infections in Common variable immunodeficiency.

COVID-19 has shed light on the role of cellular immunity in the absence of humoral response in different patient groups. Common variable immunodeficiency (CVID) is characterized by impaired humoral immunity but also an underlying T-cell dysregulation. The impact of T-cell dysregulation on cellular immunity in CVID is not clear, and this review summarizes available literature on cellular immunity in CVID with a particular focus on COVID-19. Overall mortality of COVID-19 in CVID is difficult to assess, but seems not significantly elevated, and risk factors for severe disease mirrors that of the general population, including lymphopenia. Most CVID patients have a significant T-cell response to COVID-19 disease with possible cross-reactivity to endemic coronaviruses. Several studies find a significant but impaired cellular response to basal COVID-19 mRNA vaccination that is independent of an antibody response. CVID patients with infection only have better cellular responses to vaccine in one study, but there is no clear association to T-cell dysregulation. Cellular response wane over time but responds to a third booster dose of vaccine. Opportunistic infection as a sign of impaired cellular immunity in CVID is rare but is related to the definition of the disease. CVID patients have a cellular response to influenza vaccine that in most studies is comparable to healthy controls, and annual vaccination against seasonal influenza should be recommended. More research is required to clarify the effect of vaccines in CVID with the most immediate issue being when to booster the COVID-19 vaccine.

Nationwide Utilization of Danish Government Electronic letter system for increasing inFLUenza vaccine uptake (NUDGE-FLU): Study protocol for a nationwide randomized implementation trial.

BACKGROUND: Annual influenza vaccination is widely recommended in older adults and other high-risk groups including patients with cardiovascular disease. The real-world effectiveness of influenza vaccination is limited by suboptimal uptake and effective strategies for increasing vaccination rates are therefore needed. The purpose of this trial is to investigate whether behavioral nudges digitally delivered via the Danish nationwide mandatory governmental electronic letter system can increase influenza vaccination uptake among older adults. METHODS: The NUDGE-FLU trial is a randomized implementation trial randomizing all Danish citizens aged 65 years and above without an exemption from the Danish mandatory governmental electronic letter system to receive no digitally delivered behavioral nudge (usual care arm) or to receive one of 9 electronic letters (intervention arms) each leveraging different behavioral science strategies. The trial has randomized 964,870 participants with randomization clustered at the household level (n = 691,820 households). Intervention letters were delivered on September 16, 2022, and follow-up is currently ongoing. All trial data are captured using the nationwide Danish administrative health registries. The primary end point is the receipt of an influenza vaccine on or before January 1, 2023. The secondary end point is time to vaccination. Exploratory end points include clinical events such as hospitalization for influenza or pneumonia, cardiovascular events, all-cause hospitalization, and all-cause mortality. DISCUSSION: The nationwide randomized NUDGE-FLU trial is one of the largest implementation trials ever conducted and will provide important insights into effective communication strategies to maximize vaccination uptake among high-risk groups. TRIAL REGISTRATION: Clinicaltrials.gov: NCT05542004, registered September 15, 2022, https://clinicaltrials.gov/ct2/show/NCT05542004.

Household Transmission of Influenza A Viruses in 2021-2022.

Importance: Influenza virus infections declined globally during the COVID-19 pandemic. Loss of natural immunity from lower rates of influenza infection and documented antigenic changes in circulating viruses may have resulted in increased susceptibility to influenza virus infection during the 2021-2022 influenza season. Objective: To compare the risk of influenza virus infection among household contacts of patients with influenza during the 2021-2022 influenza season with risk of influenza virus infection among household contacts during influenza seasons before the COVID-19 pandemic in the US. Design, Setting, and Participants: This prospective study of influenza transmission enrolled households in 2 states before the COVID-19 pandemic (2017-2020) and in 4 US states during the 2021-2022 influenza season. Primary cases were individuals with the earliest laboratory-confirmed influenza A(H3N2) virus infection in a household. Household contacts were people living with the primary cases who self-collected nasal swabs daily for influenza molecular testing and completed symptom diaries daily for 5 to 10 days after enrollment. Exposures: Household contacts living with a primary case. Main Outcomes and Measures: Relative risk of laboratory-confirmed influenza A(H3N2) virus infection in household contacts during the 2021-2022 season compared with prepandemic seasons. Risk estimates were adjusted for age, vaccination status, frequency of interaction with the primary case, and household density. Subgroup analyses by age, vaccination status, and frequency of interaction with the primary case were also conducted. Results: During the prepandemic seasons, 152 primary cases (median age, 13 years; 3.9% Black; 52.0% female) and 353 household contacts (median age, 33 years; 2.8% Black; 54.1% female) were included and during the 2021-2022 influenza season, 84 primary cases (median age, 10 years; 13.1% Black; 52.4% female) and 186 household contacts (median age, 28.5 years; 14.0% Black; 63.4% female) were included in the analysis. During the prepandemic influenza seasons, 20.1% (71/353) of household contacts were infected with influenza A(H3N2) viruses compared with 50.0% (93/186) of household contacts in 2021-2022. The adjusted relative risk of A(H3N2) virus infection in 2021-2022 was 2.31 (95% CI, 1.86-2.86) compared with prepandemic seasons. Conclusions and Relevance: Among cohorts in 5 US states, there was a significantly increased risk of household transmission of influenza A(H3N2) in 2021-2022 compared with prepandemic seasons. Additional research is needed to understand reasons for this association.

Designing multi-epitope mRNA construct as a universal influenza vaccine candidate for future epidemic/pandemic preparedness.

Despite the availability of prevention and treatment strategies and advancing immunization approaches, the influenza virus remains a global threat that continues to plague humanity with unpredictable pandemics. Due to the unusual genetic variability and segmented genome, the reassortment between different strains of influenza is facilitated and the viruses continuously evolve and adapt to the host cell's immunity. This underlies the seasonal vaccine mismatches that decrease the vaccine efficacy and increase the risk of outbreaks. Thus, the development of a universal vaccine covering all the influenza A and B strains would reduce the pervasiveness of the influenza virus. In the current study, a potentially universal influenza multi-epitope vaccine was designed based on the experimentally tested conserved T cell and B cell epitopes of hemagglutinin (HA), neuraminidase (NA), nucleoprotein (NP), and matrix-2 proton channel (M2) of the virus. The immune simulation and molecular docking of the vaccine construct with TLR2, TLR3, and TLR4 elicited the favorable immunogenicity of the vaccine and the formation of stable complexes, respectively. Ultimately, based on the immunoinformatics analysis, the universal mRNA multi-epitope vaccine designed in this study might have a protection potential against the various subtypes of influenza A and B.

[Expert opinion on strategies to improve vaccination coverage against seasonal influenza]. / Documento de opinión de expertos para la mejora de la cobertura vacunal frente a la gripe estacional.

Seasonal flu continues to be a major public health concern, and the influenza vaccine remains the most effective preventive measure. In Spain, vaccination coverage data from previous seasons show vaccination rates well below official targets; however, these figures improved significantly after the COVID-19 pandemic. Given the importance of achieving and maintaining high vaccination rates in order to avoid the clinical and economic impact of influenza, our multidisciplinary group of experts on vaccines analyzed the impact of low vaccination rates in Spain and drafted a series of measures to boost influenza vaccination coverage, particularly among priority groups.

Recommendations for Prevention and Control of Influenza in Children, 2022-2023.

This statement updates the recommendations of the American Academy of Pediatrics for the routine use of influenza vaccine and antiviral medications in the prevention and treatment of influenza in children during the 2022-2023 influenza season. A detailed review of the evidence supporting these recommendations is published in the accompanying technical report (http://www.pediatrics.org/cgi/doi/10.1542/peds.2022-059275). The American Academy of Pediatrics recommends annual influenza vaccination of all children without medical contraindications starting at 6 months of age. Influenza vaccination is an important strategy for protecting children and the broader community, as well as reducing the overall burden of respiratory illnesses when other viruses, including severe acute respiratory syndrome-coronavirus 2, are cocirculating. Any licensed influenza vaccine appropriate for age and health status can be administered, ideally as soon as possible in the season, without preference for one product or formulation over another. Antiviral treatment of influenza with any US Food and Drug Administration-approved, age-appropriate influenza antiviral medication is recommended for children with suspected or confirmed influenza who are hospitalized, have severe or progressive disease, or have underlying conditions that increase their risk of complications of influenza, regardless of duration of illness. Antiviral treatment should be initiated as soon as possible. Antiviral treatment may be considered in the outpatient setting for symptomatic children with suspected or confirmed influenza disease who are not at high risk for influenza complications, if treatment can be initiated within 48 hours of illness onset, and for children with suspected or confirmed influenza disease whose siblings or household contacts either are younger than 6 months or have a high-risk condition that predisposes them to complications of influenza. Antiviral chemoprophylaxis is recommended for the prevention of influenza virus infection as an adjunct to vaccination in certain individuals, especially exposed children who are at high risk for influenza complications but have not yet been immunized or who lack a sufficient immune response.

Recommendations for Prevention and Control of Influenza in Children, 2022-2023.

This technical report accompanies the recommendations of the American Academy of Pediatrics for the routine use of influenza vaccine and antiviral medications in the prevention and treatment of influenza in children during the 2022 to 2023 season. The American Academy of Pediatrics recommends annual influenza vaccination of all children without medical contraindications starting at 6 months of age. Influenza vaccination is an important strategy for protecting children and the broader community as well as reducing the overall burden of respiratory illnesses when other viruses, including severe acute respiratory syndrome-coronavirus 2, are cocirculating. This technical report summarizes recent influenza seasons, morbidity and mortality in children, vaccine effectiveness, and vaccination coverage, and provides detailed guidance on storage, administration, and implementation. The report also provides a brief background on inactivated and live attenuated influenza vaccine recommendations, vaccination during pregnancy and breastfeeding, diagnostic testing, and antiviral medications for treatment and chemoprophylaxis. Updated information is provided about the 2021 to 2022 influenza season, influenza immunization rates, the effectiveness of influenza vaccination on hospitalization and mortality, available vaccines, guidance for patients with history of severe allergic reactions to prior influenza vaccinations, and strategies to promote vaccine uptake.

Influence of influenza vaccine and comorbidity on the evolution of hospitalized COVID-19 patients. / Influencia de la vacunación antigripal y la comorbilidad en la evolución de los pacientes hospitalizados por COVID-19.

BACKGROUND AND OBJECTIVE: The COVID-19 coronavirus disease outbreak is evolving around the world. The aim of this study is to evaluate the association between influenza vaccination and the risk of mortality in hospitalized COVID-19 patients, as well as other risk factors. MATERIALS AND METHODS: Retrospective observational study. This study was conducted among hospitalized patients with COVID-19 at Hospital La Mancha Centro between March 5 and 25, 2020. Information on influenza vaccination was extracted from electronic medical records. We used a multivariate logistic regression to explore the association between influenza vaccination and mortality from COVID and other risk factors. RESULTS: 410 patients were included. Influenza vaccine had no effect among COVID-19 hospitalized patients [OR: 1.55 (95%CI: 0.96 - 2.48; p=0.071)]. Increasing hospital mortality was associated with older age [OR: 1.05 (95% CI 1.02-1.07), per year increase; p<0.001)], Charlson ≥3 [OR: 1.84 (95%CI: 1.07-3.15, p=0.027)] and heart failure on admission [OR: 6 (IC95%: 1.6 - 21.7; p=0.007)] CONCLUSIONS: Influenza vaccine had no effect among COVID-19 hospitalized patients. The risk factors identified were older age, higher comorbidity and heart failure on admission.

Influenza vaccine hesitancy and influencing factors among university students in China: a multicenter cross-sectional survey.

AIM: Highly mutable and contagious influenza poses a serious health threat to university students and their close contacts. Although annual influenza vaccination is an effective way to prevent influenza, influenza vaccination rates among Chinese university students are still low due to vaccine hesitancy. This study investigated Chinese university students' hesitancy to receive influenza vaccine and its influencing factors during the COVID-19 pandemics based on WHO's vaccine hesitancy matrix. METHODS: A multicenter cross-sectional study of university students in four cities across China was conducted via a web-based questionnaire in June 2022. Binary logistic regression was adopted to determine the factors around contextual influences, individual and group influences, and vaccines/vaccination specific issues. The reliability and validity of the questionnaire were good, with a Kronbach alpha coefficient of 0.892 and a KMO coefficient of 0.957. RESULTS: Of the 2261 Chinese university students surveyed, 44.7% had influenza vaccine hesitancy. Binary logistic regression showed that students considering high severity (OR = 0.946) or probability (OR = 0.942) of getting influenza, trusting vaccine-related advice from medical personnel (OR = 0.495) had lower odds of hesitancy. The odds of influenza vaccine hesitancy were higher if the students believed that vaccination was not necessary (OR = 4.040), had not been recommended by people around (OR = 1.476) and had no previous vaccinations or appointments (OR = 2.685). CONCLUSIONS: Medical staff are suggested to provide health education, improve doctor-patient communication and recommend vaccinations to university students to increase their risk perception and willingness to get an influenza vaccination. Collective vaccination strategies can be implemented to reduce the vaccine hesitancy for students.

An influenza hemagglutinin stem nanoparticle vaccine induces cross-group 1 neutralizing antibodies in healthy adults.

Influenza vaccines could be improved by platforms inducing cross-reactive immunity. Immunodominance of the influenza hemagglutinin (HA) head in currently licensed vaccines impedes induction of cross-reactive neutralizing stem-directed antibodies. A vaccine without the variable HA head domain has the potential to focus the immune response on the conserved HA stem. This first-in-human dose-escalation open-label phase 1 clinical trial (NCT03814720) tested an HA stabilized stem ferritin nanoparticle vaccine (H1ssF) based on the H1 HA stem of A/New Caledonia/20/1999. Fifty-two healthy adults aged 18 to 70 years old enrolled to receive either 20 µg of H1ssF once (n = 5) or 60 µg of H1ssF twice (n = 47) with a prime-boost interval of 16 weeks. Thirty-five (74%) 60-µg dose participants received the boost, whereas 11 (23%) boost vaccinations were missed because of public health restrictions in the early stages of the COVID-19 pandemic. The primary objective of this trial was to evaluate the safety and tolerability of H1ssF, and the secondary objective was to evaluate antibody responses after vaccination. H1ssF was safe and well tolerated, with mild solicited local and systemic reactogenicity. The most common symptoms included pain or tenderness at the injection site (n = 10, 19%), headache (n = 10, 19%), and malaise (n = 6, 12%). We found that H1ssF elicited cross-reactive neutralizing antibodies against the conserved HA stem of group 1 influenza viruses, despite previous H1 subtype head-specific immunity. These responses were durable, with neutralizing antibodies observed more than 1 year after vaccination. Our results support this platform as a step forward in the development of a universal influenza vaccine.