High-throughput sequencing-based neutralization assay reveals how repeated vaccinations impact titers to recent human H1N1 influenza strains.

The high genetic diversity of influenza viruses means that traditional serological assays have too low throughput to measure serum antibody neutralization titers against all relevant strains. To overcome this challenge, we developed a sequencing-based neutralization assay that simultaneously measures titers against many viral strains using small serum volumes using a workflow similar to traditional neutralization assays. The key innovation is to incorporate unique nucleotide barcodes into the hemagglutinin (HA) genomic segment, and then pool viruses with numerous different barcoded HA variants and quantify the infectivity of all of them simultaneously using next-generation sequencing. With this approach, a single researcher performed the equivalent of 2,880 traditional neutralization assays (80 serum samples against 36 viral strains) in approximately 1 month. We applied the sequencing-based assay to quantify the impact of influenza vaccination on neutralization titers against recent human H1N1 strains for individuals who had or had not also received a vaccine in the previous year. We found that the viral strain specificities of the neutralizing antibodies elicited by vaccination vary among individuals and that vaccination induced a smaller increase in titers for individuals who had also received a vaccine the previous year-although the titers 6 months after vaccination were similar in individuals with and without the previous-year vaccination. We also identified a subset of individuals with low titers to a subclade of recent H1N1 even after vaccination. We provide an experimental protocol (dx.doi.org/10.17504/protocols.io.kqdg3xdmpg25/v1) and computational pipeline (https://github.com/jbloomlab/seqneut-pipeline) for the sequencing-based neutralization assays to facilitate the use of this method by others. IMPORTANCE: We describe a new approach that can rapidly measure how the antibodies in human serum inhibit infection by many different influenza strains. This new approach is useful for understanding how viral evolution affects antibody immunity. We apply the approach to study the effect of repeated influenza vaccination.

[Vaccinations for emerging and re-emerging viral diseases]. / Impfungen für neu- und wiederauftretende Viruserkrankungen.

BACKGROUND: Emerging or re-emerging viral diseases have a pandemic potential and threaten global health. Vaccination is of crucial importance in the prevention of emerging and re-emerging viral diseases. OBJECTIVE: Description of the current status of vaccine development against Filoviridae, highly pathogenic coronaviruses, smallpox viruses, influenza viruses and arboviruses. MATERIAL AND METHODS: Focused literature search. RESULTS: The World Health Organization (WHO) regularly publishes a list of infectious diseases that are expected to pose a major threat to humanity as they are could potentially trigger new pandemics; however, in addition to these human-to-human transmissible diseases, some arboviruses also have pandemic potential. In recent years numerous new vaccines, some of which are highly effective, have been licensed against new and re-emerging viral diseases and other promising vaccine candidates are currently in development. CONCLUSION: There are still gaps in the development of vaccines in the area of Filoviridae and highly pathogenic coronaviruses. Vaccinations against smallpox viruses have been available for a long time. Developing influenza vaccines against novel strains in a timely manner is a challenge and universal influenza vaccines could be a possible solution. Modern vaccines are available against the arboviruses dengue and Chikungunya fever.

Vaccine-induced NA immunity decreases viral shedding, but does not disrupt chains of airborne transmission for the 2009 pandemic H1N1 virus in ferrets.

Split-virion-inactivated influenza vaccines are formulated based on viral hemagglutinin content. These vaccines also contain the viral neuraminidase (NA) protein, but NA content is not standardized and varies between manufacturers. In clinical studies and animal models, antibodies directed toward NA reduced disease severity and viral load; however, the impact of vaccine-induced NA immunity on airborne transmission of influenza A viruses is not well characterized. Therefore, we evaluated if vaccination against NA could disrupt chains of airborne transmission for the 2009 pandemic H1N1 virus in ferrets. Immunologically naïve donor ferrets were infected with the 2009 pandemic H1N1 virus and then paired in transmission cages with mock- or NA-vaccinated respiratory contacts. The mock- and NA-vaccinated animals were then monitored daily for infection, and once infected, these animals were paired with a naive secondary respiratory contact. In these studies, all mock- and NA-vaccinated animals became infected; however, NA-vaccinated animals shed significantly less virus for fewer days relative to mock-vaccinated animals. For the secondary contacts, 6/6 and 5/6 animals became infected after exposure to mock- and NA-vaccinated animals, respectively. To determine if vaccine-induced immune pressure selected for escape variants, we sequenced viruses recovered from ferrets. No mutations in NA became enriched during transmission. These findings indicate that despite reducing viral load, vaccine-induced NA immunity does not prevent infection during continuous airborne exposure and subsequent onward airborne transmission of the 2009 pandemic H1N1 virus. IMPORTANCE: In humans and animal models, immunity against neuraminidase (NA) reduces disease severity and viral replication during influenza infection. However, we have a limited understanding of the impact of NA immunity on viral transmission. Using chains of airborne transmission in ferrets as a strategy to simulate a more natural route of infection, we assessed if vaccine-induced NA immunity could disrupt transmission of the 2009 pandemic H1N1 virus. The 2009 pandemic H1N1 virus transmitted efficiently through chains of transmission in the presence of NA immunity, but NA-vaccinated animals shed significantly less virus and had accelerated viral clearance. To determine if immune pressure led to the generation of escape variants, viruses in ferret nasal wash samples were sequenced, and no mutations in NA were identified. These findings demonstrate that vaccine-induced NA immunity is not sufficient to prevent infection via airborne exposure and onward airborne transmission of the 2009 pandemic H1N1 virus.

Investigating the influencing factors of vaccination decisions for newly developed and established vaccines: a comparative study based on latent class logit models in China.

Background: The factors influencing vaccination decision-making for newly developed vaccines may be similar to and different from those for established vaccines. Understanding these underlying differences and similarities is crucial for designing targeted measures to promote new vaccines against potential novel viruses. Objective: This study aims to compare public vaccination decisions for newly developed and established vaccines and to identify the differences and similarities in the influencing factors. Method: A discrete choice experiment (DCE) was conducted on 1,509 representatives of the general population in China to collect data on preferences for the coronavirus disease 2019 (COVID-19) and influenza vaccines, representing the newly developed and established vaccines, respectively. The latent class logit model was used to identify latent classes within the sample, allowing for an analysis of the factors distinctly influencing choices for both types of vaccines. Result: Participants valued similar attributes for both vaccines. However, concerns about sequelae were more significant for the newly developed vaccine, while effectiveness was prioritized for the established vaccine. Class membership analysis revealed these differences and similarities were significantly correlated with age, health, yearly household income, acquaintances' vaccination status, and risk perception. Conclusion: The study highlights the need for tailored communication strategies and targeted vaccination interventions. For the newly developed vaccines, addressing concerns about side effects is more crucial. For long-standing vaccines, emphasizing their effectiveness can enhance uptake more significantly. Engaging healthcare providers and community influencers is essential for both vaccines to increase public confidence and vaccination rates. Clear communication and community engagement are critical strategies for addressing public concerns and misinformation, particularly during periods of heightened concern.

A Call for Adopting High-Dose Influenza Vaccines for Adults Aged 65 and Above in Gulf Cooperation Council (GCC) Countries.

Seasonal influenza poses significant health and economic challenges globally each year, particularly impacting the elderly population (aged ≥ 65 years) with increased rates of hospitalization, and mortality. The population of older adults is steadily increasing in the Gulf Cooperation Council (GCC) countries and is likely to increase even further. In addition, there is a high burden of chronic comorbidities in these countries like diabetes and obesity, which increases the likelihood of severe consequences of influenza infection. The GCC countries also host mass gathering events like Hajj, Umrah pilgrimage, Arba'een (nearby Iraq) pilgrimage, and international sports and business events, which further intensify the risk of outbreaks like influenza. These events facilitate the mixing of visitors from various countries. Thus, influenza activity in this North Hemisphere (NH) geography is usually present even before the availability of NH seasonal influenza vaccine. This is especially problematic for the elderly, whose protection from the previous year's immunization would have waned. Higher dosages of antigens or adjuvants have been used to improve immunogenicity in older people with superior vaccine effectiveness. Therefore, there is a compelling argument in favor of the implementation of high-dose seasonal influenza vaccines in the GCC countries to improve the protection of individuals aged 65 years and older against influenza infection and associated severe complications.

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.

Association Between Influenza Vaccination and Acute Kidney Injury Among the Elderly: A Self-Controlled Case Series.

BACKGROUND: Several cases of renal complications, including acute kidney injury (AKI), after influenza vaccination have been reported, but the association remains unproven. We evaluated the association between influenza vaccination and AKI occurrence among the Korean elderly in the 2018-2019 and 2019-2020 seasons. METHODS: We used a large database combining vaccination registration data from the Korea Disease Control and Prevention Agency and claims data from the National Health Insurance Service. The study subjects were patients hospitalized with AKI for the first-time following vaccination among those who received one influenza vaccine in the 2018-2019 or 2019-2020 season. Only those aged 65 or older at the date of vaccination were included. We performed a self-controlled case series study, designating the risk period as 1 to 28 days post-vaccination and the observation period as each influenza season. The adjusted incidence rate ratio (aIRR) was calculated by adjusting for nephrotoxic drug use and influenza infection that may influence AKI occurrence using a conditional Poisson regression model. RESULTS: A total of 16 713 and 16 272 AKI events were identified during the 2018-2019 and 2019-2020 seasons, respectively. The aIRR for AKI was 0.83 (95% confidence interval [CI] = 0.79-0.87) in the 2018-2019 season. The aIRR for the 2019-2020 influenza season was similar to the 2018-2019 season (aIRR = 0.86; 95% CI = 0.82-0.90). CONCLUSIONS: Influenza vaccination is associated with a lower risk of AKI in the elderly over 65. This evidence supports the recommendation of annual influenza vaccination for the elderly. Further studies are needed to determine the biological mechanisms linking the influenza vaccine and AKI.

Comparison of healthcare resource use and cost between influenza and COVID-19 vaccine coadministration and influenza vaccination only.

OBJECTIVE: To compare healthcare resource utilization (HCRU) and all-cause medical costs among individuals aged ≥50 years who received influenza and COVID-19 vaccines on the same day and those who received influenza vaccine only. METHODS: We conducted a retrospective cohort study leveraging Optum's de-identified Clinformatics DataMart from 8/31/2021 to 7/31/2023. Individuals aged ≥50 years continuously enrolled in health plans for 1 year prior and until 7/31/2023 were included. Two cohorts were formed based on vaccination status between 8/31/2022 and 1/31/2023: co-administered influenza and COVID-19 vaccines (co-admin cohort) and influenza vaccine only (influenza cohort). Associations between vaccination status and all-cause, influenza-related, COVID-related, pneumonia-related, and cardiorespiratory-related hospitalization, outpatient or emergency room visits and all-cause medical costs were estimated by weighted generalized linear models, adjusting for confounding by stabilized inverse probability of treatment weighting. RESULTS: 613,156 (mean age: 71) and 1,340,011 (mean age: 72) individuals were included in the co-admin and influenza cohorts, respectively. After weighting, the baseline characteristics were balanced between cohorts. The co-admin cohort was at statistically significant lower risk of all-cause (RR: 0.95, 95% CI: 0.93-0.96), COVID-19-related (RR: 0.59, 95% CI: 0.56-0.63), cardiorespiratory-related (RR: 0.94, 95% CI: 0.93-0.96) and pneumonia-related (RR: 0.86, 95% CI: 0.83-0.90) hospitalization but not influenza-related hospitalizations (RR: 0.91, 95% CI: 0.81, 1.04) compared with the influenza cohort. Co-administration was associated with 3% lower all-cause medical cost (cost ratio: 0.974, 95% CI: 0.968, 0.979) during the follow-up period compared to receiving influenza vaccine only. LIMITATIONS: Limitations include the potential residual confounding bias in observational data, measurement errors from claims data, and that the cohort was followed for a single season. CONCLUSION: Receiving co-administered COVID-19 and influenza vaccines versus only receiving influenza vaccination reduced the risk of HCRU, especially COVID-19-related hospitalization and all-cause medical costs. Increasing vaccine coverage, particularly for COVID-19, might have public health and economic benefits.

Effects of adding antibiotics to an inactivated oil-adjuvant avian influenza vaccine on vaccine characteristics and chick health.

During poultry immunization, antibiotics are typically added to inactivated oil-adjuvant avian influenza (AI) vaccines. Here, we evaluated the effects of adding ceftiofur, a third-generation cephalosporin, to an AI vaccine on vaccine stability and structure and on chick growth, immune efficacy, blood concentrations, biochemical and immunological indices, and gut microbiota. The results demonstrated that neither aqueous ceftiofur sodium nor ceftiofur hydrochloride oil emulsion formed a stable mixture with the vaccine. Adding ceftiofur formulations, particularly ceftiofur hydrochloride, at >4% significantly destabilized the vaccine's water-in-oil structures. Adding ceftiofur also increased vaccine malabsorption at the injection site; specifically, adding ceftiofur hydrochloride reduced H5N8 and H7N9 antibody titers after the first immunization (P < 0.05) and H7N9 antibody titers after the second immunization (P < 0.01). Serum drug concentrations did not differ significantly between the groups with ceftiofur sodium and hydrochloride addition. Ceftiofur addition increased postvaccination chick weight loss; compared with the vaccine alone, ceftiofur sodium-vaccine mixture increased chick weight significantly (P < 0.05). Ceftiofur addition also increased stress indices and reduced antioxidant capacity significantly (P < 0.05 or P < 0.01). Vaccination-related immune stress reduced gut microbiota diversity in chicks; ceftiofur addition reversed this change. AI vaccine immunization significantly reduced the relative abundance of Lactobacillus and Muribaculaceae but significantly increased that of Bacteroides and Eubacterium coprostanoligenes group. Ceftiofur addition restored the gut microbiota structure; in particular, ceftiofur hydrochloride addition significantly increased the abundance of the harmful gut microbes Escherichia-Shigella and Enterococcus, whereas ceftiofur sodium addition significantly reduced it. The changes in gut microbiota led to alterations in metabolic pathways related to membrane transport, amino acids, and carbohydrates. In conclusion, adding ceftiofur to the AI vaccine had positive effects on chick growth and gut microbiota modulation; however, different antibiotic concentrations and formulations may disrupt vaccine structure, possibly affecting vaccine safety and immunization efficacy. Thus, the addition of antibiotics to oil-adjuvant vaccines is associated with a risk of immunization failure and should be applied to poultry with caution.

Avian Influenza Virus A(H5Nx) and Prepandemic Candidate Vaccines: State of the Art.

Avian influenza virus has been long considered the main threat for a future pandemic. Among the possible avian influenza virus subtypes, A(H5N1) clade 2.3.4.4b is becoming enzootic in mammals, representing an alarming step towards a pandemic. In particular, genotype B3.13 has recently caused an outbreak in US dairy cattle. Since pandemic preparedness is largely based on the availability of prepandemic candidate vaccine viruses, in this review we will summarize the current status of the enzootics, and challenges for H5 vaccine manufacturing and delivery.

Comparison of Post-Vaccination Cellular Immune Response in Patients with Common Variable Immune Deficiency.

BACKGROUND: The problem of identifying vaccine-specific T-cell responses is still a matter of debate. Currently, there are no universal, clearly defined, agreed upon criteria for assessing the effectiveness of vaccinations and their immunogenicity for the cellular component of immunity, even for healthy people. But for patients with inborn errors of immunity (IEI), especially those with antibody deficiencies, evaluating cellular immunity holds significant importance. AIM: To examine the effect of one and two doses of inactivated adjuvanted subunit influenza vaccines on the expression of endosomal Toll-like receptors (TLRs) on the immune cells and the primary lymphocyte subpopulations in patients with common variable immunodeficiency (CVID). MATERIALS AND METHODS: During 2018-2019, six CVID patients received one dose of a quadrivalent adjuvanted influenza vaccine; in 2019-2020, nine patients were vaccinated with two doses of a trivalent inactivated influenza vaccine. The proportion of key lymphocyte subpopulations and expression levels of TLRs were analyzed using flow cytometry with monoclonal antibodies. RESULTS: No statistically significant alterations in the absolute values of the main lymphocyte subpopulations were observed in CVID patients before or after vaccination with the different immunization protocols. However, after vaccination, a higher expression of TLR3 and TLR9 in granulocytes, monocytes, and lymphocytes was found in those patients who received two vaccine doses rather than one single dose. CONCLUSION: This study marks the first instance of using a simultaneous two-dose vaccination, which is associated with an elevated level of TLR expression in the immune cells. Administration of the adjuvanted vaccines in CVID patients appears promising. Further research into their impact on innate immunity and the development of more effective vaccination regimens is warranted.

Characteristics and factors of repeated influenza vaccination among elderly individuals in Shanghai, China from 2020 to 2022.

Elderly individuals face a high risk of hospitalization and death related to influenza, thus prioritizing them for influenza vaccination. Due to variations in the influenza virus and waning protective antibodies, annual influenza vaccination is recommended. However, research on repeated influenza vaccination among elderly individuals in China is limited. From 2020 to 2022, the average influenza vaccination coverage among registered elderly individuals in Shanghai was 4.1%, showing a declining trend over time. In 2020, the rate of repeated influenza vaccination among elderly individuals was 28.35%, which rose to almost two-thirds both in 2021 and 2022. No increased risk of adverse events following immunization was observed after repeated influenza vaccination during this period. Our study also found that elderly individuals with Shanghai household registration, managed by community clinics, and older age tended to receive more doses of repeated influenza vaccination throughout the period from 2020 to 2022. Increasing influenza vaccine coverage among elderly individuals in Shanghai is both urgent and challenging. Health authorities should intensify educational and promotional campaigns to encourage uptake of annual repeated influenza vaccination among elderly individuals.

Influenza Virus-Derived CD8 T Cell Epitopes: Implications for the Development of Universal Influenza Vaccines.

The influenza virus poses a global health burden. Currently, an annual vaccine is used to reduce influenza virus-associated morbidity and mortality. Most influenza vaccines have been developed to elicit neutralizing Abs against influenza virus. These Abs primarily target immunodominant epitopes derived from hemagglutinin (HA) or neuraminidase (NA) of the influenza virus incorporated in vaccines. However, HA and NA are highly variable proteins that are prone to antigenic changes, which can reduce vaccine efficacy. Therefore, it is essential to develop universal vaccines that target immunodominant epitopes derived from conserved regions of the influenza virus, enabling cross-protection among different virus variants. The internal proteins of the influenza virus serve as ideal targets for universal vaccines. These internal proteins are presented by MHC class I molecules on Ag-presenting cells, such as dendritic cells, and recognized by CD8 T cells, which elicit CD8 T cell responses, reducing the likelihood of disease and influenza viral spread by inducing virus-infected cell apoptosis. In this review, we highlight the importance of CD8 T cell-mediated immunity against influenza viruses and that of viral epitopes for developing CD8 T cell-based influenza vaccines.

rAAV expressing a COBRA-designed influenza hemagglutinin generates a protective and durable adaptive immune response with a single dose.

Influenza remains a worldwide public health threat. Although seasonal influenza vaccines are currently the best means of preventing severe disease, the standard-of-care vaccines require frequent updating due to antigenic drift and can have low efficacy, particularly in vulnerable populations. Here, we demonstrate that a single administration of a recombinant adenovirus-associated virus (rAAV) vector expressing a computationally optimized broadly reactive antigen (COBRA)-derived influenza H1 hemagglutinin (HA) induces strongly neutralizing and broadly protective antibodies in naïve mice and ferrets with pre-existing influenza immunity. Following a lethal viral challenge, the rAAV-COBRA vaccine allowed for significantly reduced viral loads in the upper and lower respiratory tracts and complete protection from morbidity and mortality that lasted for at least 5 months post-vaccination. We observed no signs of antibody waning during this study. CpG motif enrichment of the antigen can act as an internal adjuvant to further enhance the immune responses to allow for lower vaccine dosages with the induction of unique interferon-producing CD4+ and CD8+ T cells specific to HA head and stem peptide sequences. Our studies highlight the utility of rAAV as an effective platform to improve seasonal influenza vaccines. IMPORTANCE: Developing an improved seasonal influenza vaccine remains an ambitious goal of researchers and clinicians alike. With influenza routinely causing severe epidemics with the potential to rise to pandemic levels, it is critical to create an effective, broadly protective, and durable vaccine to improve public health worldwide. As a potential solution, we created a rAAV viral vector expressing a COBRA-optimized influenza hemagglutinin antigen with modestly enriched CpG motifs to evoke a robust and long-lasting immune response after a single intramuscular dose without needing boosts or adjuvants. Importantly, the rAAV vaccine boosted antibody breadth to future strains in ferrets with pre-existing influenza immunity. Together, our data support further investigation into the utility of viral vectors as a potential avenue to improve our seasonal influenza vaccines.

Adverse Effects Related to Paediatric Influenza Vaccination and Its Influence on Vaccination Acceptability. The FLUTETRA Study: A Survey Conducted in the Region of Murcia, Spain.

BACKGROUND: During the 2022-23 season, three autonomous communities recommended influenza vaccination for all children between 6 and 59 months. The objective is to evaluate the adverse effects associated with the administered influenza vaccines in the Region of Murcia, as well as their influence on the recommendation of the same to acquaintances or repetition in future seasons. MATERIAL AND METHODS: Cross-sectional descriptive study with an online questionnaire sent to the parents of vaccinated minors of 6-23 months of age receiving inactivated intramuscular vaccine (IIV) or 24-59 months of age receiving live-attenuated intranasal vaccine (LAIV). RESULTS: Among 4971 surveys received, the most common adverse effect for LAIV and IIV was runny nose (40.90%) and local pain (31.94%), respectively. Sixty percent of adverse effects lasted ≤ 1 day, and around 10% lasted ≥ 3 days. The interference of adverse effects with the minor's daily life was very infrequent (3.32%), as was the need for visiting the medical office (2.68%). Overall, 96.44% of parents would recommend influenza vaccination to friends and relatives after the experience. Only 3.56% would not recommend it, while 1.68% would not vaccinate their child against influenza again. The most frequently cited reason being adverse effects. CONCLUSIONS: Our study shows the safety of influenza vaccines. Despite the low impact of adverse effects, they influence some parents in their intention to continue vaccinating or recommending it to acquaintances, which remarks the need to reinforce the information given to parents so that this fact does not influence decision-making.

Evidence base for yearly respiratory virus vaccines: Current status and proposed improved strategies.

Annual vaccination is widely recommended for influenza and SARS-CoV-2. In this essay, we analyse and question the prevailing policymaking approach to these respiratory virus vaccines, especially in the United States. Every year, licensed influenza vaccines are reformulated to include specific strains expected to dominate in the season ahead. Updated vaccines are rapidly manufactured and approved without further regulatory requirement of clinical data. Novel vaccines (i.e. new products) typically undergo clinical trials, though generally powered for clinically unimportant outcomes (e.g. lab-confirmed infections, regardless of symptomatology or antibody levels). Eventually, the current and future efficacy of influenza and COVID-19 vaccines against hospitalization or death carries considerable uncertainty. The emergence of highly transmissible SARS-CoV-2 variants and waning vaccine-induced immunity led to plummeting vaccine effectiveness, at least against symptomatic infection, and booster doses have since been widely recommended. No further randomized trials were performed for clinically important outcomes for licensed updated boosters. In both cases, annual vaccine effectiveness estimates are generated by observational research, but observational studies are particularly susceptible to confounding and bias. Well-conducted experimental studies, particularly randomized trials, are necessary to address persistent uncertainties about influenza and COVID-19 vaccines. We propose a new research framework which would render results relevant to the current or future respiratory viral seasons. We demonstrate that experimental studies are feasible by adopting a more pragmatic approach and provide strategies on how to do so. When it comes to implementing policies that seriously impact people's lives, require substantial public resources and/or rely on widespread public acceptance, high evidence standards are desirable.

Influenza virus circulation and vaccine effectiveness during June 2021-May 2023 in Thailand.

Thai Ministry of Public Health recommends influenza vaccination for certain risk groups. We evaluated 2023 Southern Hemisphere influenza vaccine effectiveness against medically attended influenza using surveillance data from nine Thai hospitals and a test-negative design. During June 2022-May 2023, influenza vaccine provided moderate protection against seeking care for influenza illness (adjusted vaccine effectiveness 51%; 95% confidence interval 28-67). Understanding vaccine effectiveness can help guide future antigen selection and support clinicians to make a strong influenza vaccine recommendation to patients.

Medical and dental student knowledge about COVID-19 and influenza vaccines impact opinions about vaccine advocacy and future practice.

Introduction: The World Health Organization has identified vaccine hesitancy as a global public health challenge. Healthcare providers are among the most influential and trusted figures for vaccine counseling. This article focuses on COVID-19 and influenza personal immunization behaviors, vaccine knowledge and opinions, and vaccine counseling confidence among future healthcare providers - dental and medical students. Methods: A cross-sectional anonymous online survey was conducted at four dental schools and one allopathic medical school in the United States. Items included personal vaccination status for the COVID-19 and influenza vaccines and vaccine-specific items developed based on past research to assess knowledge, opinions, and behaviors. Results: Two hundred and thirty-two medical and 221 dental students completed the survey. 68 and 55% scored average/above-average knowledge on COVID-19 and influenza vaccine items, respectively. There were significant differences between those with average/above-average and below-average knowledge scores regarding learning about, recommending, and advocating for vaccines and counseling vaccine-hesitant patients for both vaccines (p < 0.0001). Although higher-knowledge students had higher vaccination rates (p < 0.0001), many had insufficient knowledge about vaccines. Discussion: Healthcare providers play a crucial role in vaccine advocacy. The identified knowledge gaps are significant as they impact quality of patient care. And opinions about future vaccination practice such as recommending, providing, and counseling about vaccines. Equipping students with knowledge and communication skills will enable them to be strong vaccine advocates to improve overall public health.

The Attitudes of Healthcare Professionals in an Autonomous Community in Spain towards Paediatric Influenza Vaccination.

In the 2022-2023 influenza season, three autonomous communities anticipated the document approved by the Public Health Commission recommending influenza vaccination for all children aged 6 to 59 months. The primary objective of this study was to evaluate the attitude of healthcare professionals towards the first universal vaccination campaign in our region, as well as the acceptability of the vaccines used and their attitude towards pilot school vaccination. This was a cross-sectional, survey-based, descriptive study. All healthcare professionals involved in the campaign were invited to participate. Overall, 91.9% of surveyed professionals thought that influenza vaccination from 6 to 59 months was important or very important, and 89.8% had previous experience regarding the intramuscular vaccine. Healthcare professionals rated the intranasal vaccine significantly more positively, but there were no differences when asking about each vaccine without comparison. The inhaled vaccine was preferred by 97.5% for the following campaign. Pilot school vaccination had a 75% acceptance rate. The inhaled vaccine was preferred by most professionals, and pilot school vaccination was highly accepted and independently associated with the importance of vaccination as considered by physicians, being a medical doctor, and participation in the pilot programme.

Intent to receive flu vaccine and influenza vaccination coverage among health professionals during 2019, 2020 and 2021 campaigns in Côte d'Ivoire.

Vaccination of healthcare workers against influenza is a crucial strategy to reduce transmission amongst vulnerable populations, facilitate patient uptake of vaccination, and bolster pandemic preparedness. Globally, vaccination coverage of health workers varied from 10 % to 88 %. Understanding health workers' knowledge and acceptance of the influenza vaccine, particularly among physicians, is crucial for the fine-tuning and continued success of influenza vaccination campaigns. We conducted a cross-sectional survey of 472 health workers in Abidjan, Côte d'Ivoire, to inform subsequent subnational and national introductions of influenza vaccine and subsequent campaigns targeting health workers in 2019 (14302), 2020 (14872), and 2021 (24473). Using a purposive sample of university hospitals, general hospitals, rural, and urban health facilities, we interviewed a convenience sample of health workers aged 18 years and older. Physicians had the lowest intention to receive the influenza vaccine (58 %), while nurses (78 %) and midwives (76 %) were the most willing. Across all occupations, intention to receive vaccination increased if the vaccine was offered for free or if recommended by the Ministry of Health. 76 % of respondents believed that the influenza vaccine could prevent illness in health workers. Communication strategies, including about the benefits of influenza vaccination, could raise awareness and acceptance among health workers prior to vaccination campaigns. Influenza vaccination coverage rates between 2019 and 2021 were on par with rates of intention to receive vaccination in the 2018 survey; in 2019, 2020, and 2021, coverage among physicians was 73 %, 73 %, and 52 % and coverage among nurses and midwives was 86 %, 86 %, and 74 % respectively. Improving health workers' knowledge and acceptance of the influenza vaccine, particularly among physicians, is crucial for the continued success of influenza vaccination campaigns.