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

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

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

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

Changes in Attitudes and Barriers to Seasonal Influenza Vaccination from 2007 to 2023.

This study investigated how factors and barriers to flu vaccination among college students has changed over the past 16 years. Data were collected from 440 students using a survey and compared to previous data from the same university. Respondents were also asked about their experiences with Covid-19 and its effect on their intent to vaccinate. We found that vaccination rates had increased from 12.4 to 30.5%. Among the unvaccinated, expense, fear of getting influenza from vaccination, fear of side effects, and lack of information have decreased by 28%, 20%, 17%, and 15% respectively. Time, convenience, and perceived risk are still significant barriers to vaccination. Students are getting more encouragement to vaccinate from their health care providers and parents, but it is becoming less effective. The Covid-19 pandemic has changed vaccine attitudes and vaccine fatigue has been a large contributor. Additionally, political affiliation has become a predictor of flu vaccine uptake with conservatives being less likely to vaccinate. There has also been a shift in motivation from concern for personal safety to concern for public safety.

What explains racial/ethnic inequities in the uptake of differentiated influenza vaccines?

We investigated the role of individual, community and vaccinator characteristics in mediating racial/ethnic disparities in the uptake of differentiated influenza vaccines (DIVs; including high-dose, adjuvanted, recombinant and cell-based vaccines). We included privately-insured (commercial and Medicare Advantage) ≥65 years-old community-dwelling health plan beneficiaries in the US with >1 year of continuous coverage and who received ≥1 influenza vaccine during the study period (July 2014-June 2018). Of 2.8 million distinct vaccination claims, 60% were for DIVs; lower if received in physician offices (49%) compared to pharmacies/facilities (74%). Among those vaccinated in physician offices, non-whites had lower odds of receiving a DIV if they lived in a non-minority county (0.77;95%CI 0.75-0.80) and even lower odds if they lived in a minority county (0.62;0.60-0.63). Differences in education, household income, medical history, community and vaccinator characteristics did not fully explain the disparities. Similar patterns emerged for vaccinations in pharmacies/facilities, although disparities disappeared altogether after controlling for socio-economic and vaccinator characteristics. When vaccinated in physician offices, minority county residents were less likely to receive a DIV, especially for non-whites (0.72;0.67-0.78). These disparities disappeared for whites, but not for non-whites, after controlling for community and vaccinator characteristics. We found an alarming level of inequity in DIV vaccine uptake among fully insured older adults that could not be fully explained by differences in sociodemographic, medical, community, and vaccinator characteristics. New strategies are urgently needed to address these inequities.

Effectiveness of influenza and pneumococcal vaccines on chronic obstructive pulmonary disease exacerbations.

BACKGROUND AND OBJECTIVE: Single-study evidence of separate and combined effectiveness of influenza and pneumococcal vaccination in patients with chronic obstructive pulmonary disease (COPD) is limited. To fill this gap, we studied the effectiveness of trivalent seasonal influenza vaccine (TIV) and 23-valent pneumococcal polysaccharide vaccine (PPSV23), separately and together, at preventing adverse COPD outcomes. METHODS: Our study used a self-controlled, before-and-after cohort design to assess the effectiveness of TIV and PPSV23 in COPD patients. Patients were recruited from hospitals in Tangshan City, Hebei Province, China. Subjects self-selected into one of the three vaccination schedules: TIV group, PPSV23 group and TIV&PPSV23 group. We used a physician-completed, medical record-verified questionnaire to obtain data on acute exacerbations of COPD (AECOPD), pneumonia and related hospitalization. Vaccine effectiveness was determined by comparing COPD outcomes before and after vaccination, controlling for potential confounding using Cox regression. RESULTS: We recruited 474 COPD patients, of whom 109 received TIV, 69 received PPSV23 and 296 received TIV and PPSV23. Overall effectiveness for preventing AECOPD, pneumonia and related hospitalization were respectively 70%, 59% and 58% in the TIV group; 54%, 53% and 46% in the PPSV23 group; and 72%, 73% and 69% in the TIV&PPSV23 group. The vaccine effectiveness without COVID-19 non-pharmaceutical intervention period were 84%, 77% and 88% in the TIV group; 63%, 74% and 66% in the PPSV23 group; and 82%, 83% and 91% in the TIV&PPSV23 group. CONCLUSION: Influenza vaccination and PPSV23 vaccination, separately and together, can effectively reduce the risk of AECOPD, pneumonia and related hospitalization. Effectiveness for preventing AECOPD was the greatest.

Reduced Influenza B-Specific Postvaccination Antibody Cross-reactivity in the B/Victoria Lineage-Predominant 2019/20 Season.

BACKGROUND: The influenza activity of the 2019/20 season remained high and widespread in the United States with type B viruses predominating the early season. The majority of B viruses characterized belonged to B/Victoria (B/Vic) lineage and contained a triple deletion of amino acid (aa) 162-164 in hemagglutinin (3DEL). These 3DEL viruses are antigenically distinct from B/Colorado/06/2017 (CO/06)-the B/Vic vaccine component of the 2018/19 and 2019/20 seasons representing the viruses with a double deletion of aa 162-163 in hemagglutinin (2DEL). METHODS: We performed molecular characterization and phylogenetic analysis of circulating B/Vic viruses. We also conducted hemagglutination inhibition (HAI) assay using archived human postvaccination sera collected from healthy subjects administered with different types of 2018/19 or 2019/20 seasonal vaccines. Their HAI cross-reactivity to representative 3DEL viruses was analyzed. RESULTS: The CO/06-specific human postvaccination sera, after being adjusted for vaccine type, had significantly reduced HAI cross-reactivity toward representative 3DEL viruses, especially the 136E+150K subgroup. The geometric mean titers against 3DEL viruses containing 136E+150K mutations were 1.6-fold lower in all populations (P = .051) and 1.9-fold lower in adults (P = .016) compared with those against the 136E+150N viruses. CONCLUSIONS: Our results indicate that postvaccination antibodies induced by the B/Vic vaccine component of the 2019/20 influenza season had reduced HAI cross-reactivity toward predominant 3DEL viruses in the United States. A close monitoring of the 3DEL 136E+150K subgroup is warranted should this subgroup return and predominate the 2020/21 influenza season.

Sociodemographic and health-related determinants of seasonal influenza vaccination in pregnancy: A systematic review and meta-analysis of the evidence since 2000.

INTRODUCTION: Vaccination is considered to be the most practical and effective preventative measure against influenza. It is highly recommended for population subgroups most at risk of developing complications, including pregnant women. However, seasonal influenza vaccine uptake remains suboptimal among pregnant women, even in jurisdictions with universal vaccination. We summarized the evidence on the determinants of seasonal influenza vaccine uptake during pregnancy to better understand factors that influence vaccine uptake among pregnant women. MATERIAL AND METHODS: We systematically searched MEDLINE, Embase and CINAHL from January 2000 to February 2020 for publications in English reporting on sociodemographic and/or health-related determinants of seasonal influenza vaccine uptake during pregnancy. Two reviewers independently included studies. One reviewer extracted data and assessed study quality, and another reviewer checked extracted data and study quality assessments for errors. Disagreements were resolved through consensus, or a third reviewer. We meta-analyzed using the inverse variance, random-effects method, and reported the odds ratios (OR) and 95% confidence intervals (CI). RESULTS: From 1663 retrieved citations, we included 36 studies. The following factors were associated with increased seasonal influenza vaccine uptake: Older age (20 studies: OR 1.13, 95% CI 1.07-1.20), being nulliparous (13 studies: OR 1.26, 95% CI 1.15-1.38), married (8 studies: OR 1.11, 95% CI 1.07-1.15), employed (4 studies: OR 1.13, 95% CI 1.02-1.24), a non-smoker (8 studies: OR 1.25, 95% CI 1.04-1.51) and having prenatal care (3 studies: OR 3.36, 95% CI 2.25-5.02), a chronic condition (6 studies: OR 1.30, 95% CI 1.17-1.44), been previously vaccinated (9 studies: OR 4.88, 95% CI 3.14-7.57) and living in a rural area (9 studies: OR 1.09, 95% CI 1.05-1.14). Compared with being black, being white was also associated with increased seasonal influenza vaccine uptake (11 studies: OR 1.30, 95% CI 1.20-1.41). CONCLUSIONS: The evidence suggests that several sociodemographic and health-related factors may determine seasonal influenza vaccination in pregnancy, and that parity, history of influenza vaccination, prenatal care and comorbidity status may be influential.

Differential Antibody Recognition of H3N2 Vaccine and Seasonal Influenza Virus Strains Based on Age, Vaccine Status, and Sex in the 2017-2018 Season.

BACKGROUND: An antigenic mismatch between the vaccine and circulating H3N2 strains was hypothesized to contribute to the severity of the 2017-2018 season in North America. METHODS: Serum and nasal washes were collected from influenza positive and negative patients during the 2017-2018 season to determine neutralizing antibody (nAb) titers and for influenza virus sequencing, respectively. RESULTS: The circulating and vaccine H3N2 virus strains were different clades, with the vaccine strain being clade 3C.2a and the circulating viruses being 3C.2a2 or 3C.3a. At enrollment, both the H3N2 negative and positive patients had greater nAb titers to the egg-adapted vaccine virus compared to the cell-grown vaccine but the H3N2-negative population had significantly greater titers to the circulating 3C.2a2. Among H3N2-positive patients, vaccination, younger age, and female sex were associated with greater nAb responses to the egg-adapted vaccine H3N2 virus but not to the cell-grown vaccine or circulating viruses. CONCLUSIONS: For the 2017-2018 circulating viruses, mutations introduced by egg adaptation decreased vaccine efficacy. No increased protection was afforded by vaccination, younger age, or female sex against 2017-2018 circulating H3N2 viruses.

Determination of the potency of a cell-based seasonal quadrivalent influenza vaccine using a purified primary liquid standard.

In Japan, the practical application of completely cell-based seasonal influenza vaccines is under consideration. Considering the good correlation between the immunogenicity of egg-based influenza vaccines and the hemagglutinin (HA) content determined by the single radial immunodiffusion (SRD) assay, we determined the potency of the first cell-based quadrivalent vaccine experimentally generated in Japan using the SRD assay in this study. A primary liquid standard (PLS) and reference antigen were generated from the purified vaccine virus, and a sheep antiserum was produced against the HA of the vaccine virus. Since the purity of the PLS affects the reliability of vaccine potency testing, the purification steps are significant. We successfully prepared a purified PLS nearly free of cell debris. The HA content in the PLS was first estimated from the total amount of viral protein and the percentage of HA content determined by SDS-PAGE analysis. The HA content in the reference antigen was calibrated to that in the PLS via the SRD assay. The vaccine potency, that is, the HA content in each vaccine, was finally measured using the corresponding reference antigen. Ultimately, the measured vaccine potency of the monovalent vaccine was similar to that of the quadrivalent vaccine.

A phase III, open-label, single-arm, study to evaluate the safety and immunogenicity of a trivalent, surface antigen inactivated subunit influenza virus vaccine produced in mammalian cell culture (Optaflu®) in healthy adults.

Vaccination is an essential tool in reducing the impact of seasonal influenza infections. The viral strains responsible for seasonal outbreaks vary annually, and preventive vaccines have to be adapted accordingly. The aim of this study was to evaluate the safety, clinical tolerability and the antibody response to each of the three influenza vaccine antigens after vaccination with a cell-derived, trivalent, surface antigen, inactivated influenza vaccine (TIVc), as measured by single radial haemolysis (SRH) or haemagglutination inhibition (HI) assay in accordance with European Union licensing guidelines in place for years 2013/2014. This phase 3, open-label, single-arm study enrolled 126 healthy adults divided into two age groups (63 subjects aged 18 to ≤ 60 years and 63 subjects aged ≥ 61 years). Antibody titres were measured before and 21 days after vaccination. Adverse events were determined using diary cards, interviews and reviews of the available medical records. One subject was lost to follow-up and three subjects had protocol deviations. Following vaccination, protective HI antibody titres (≥ 1:40) were detected in 100%, 97%, and 94% of the younger adults (18-≤ 60 years) and in 97%, 95%, and 80% of the older adults (≥ 61 years) against the A (H1N1), A (H3N2), and B influenza strains respectively. The antibody response licensing criteria were met in both age groups. Solicited adverse events were reported by 57% subjects 18 to ≤ 60 years and 35% subjects ≥ 61 years. Among the younger adults 51% had local and 27% had systemic adverse events, whereas of the older subjects 29% had local and 13% had systemic adverse events (mainly injection site pain or headache in both age groups). Unsolicited adverse events at least possibly related to the vaccine were mild and detected in 3% of the younger adults and none of the older adults. Overall, the trivalent, surface antigen, inactivated subunit influenza virus vaccine produced in mammalian cell culture proved to be safe and immunogenic in younger and older healthy adults.

Attitudes and barriers associated with seasonal influenza vaccination uptake among public health students; a cross-sectional study.

BACKGROUND: Although research has explored influenza vaccination uptake among medical and college students, there is a dearth of research in understanding influenza vaccination uptake and attitudes toward the vaccine among future public health practitioners. Undergraduate public health students represent future public health practitioners who may be a significant educational resource for health information, including the importance of vaccinations. METHODS: This cross-sectional study utilized survey data from 158 undergraduate public health students attending a large public university in Southern California. The survey assessed public health students' attitudes and beliefs towards the seasonal influenza vaccine and seasonal vaccination rates among this population. RESULTS: Over 88% of respondents reported having been encouraged to receive the seasonal influenza vaccine, while only 43.0% reported receipt. Of the students who reported not receiving the vaccine, 49.4% believed it may give them the flu, 30.4% believed there may be dangerous side effects, and 28.9% believed they were not at risk for contracting the flu. Access to health care practitioners (OR: 3.947, 95% CI [1.308-11.906]) and social encouragement (OR: 3.139, 95% CI [1.447-6.811]) were significantly associated with receipt of the seasonal influenza vaccine. CONCLUSION: As public health program curriculum includes information about seasonal influenza vaccination and 68% of the sample were seniors soon to be exiting the program with an undergraduate degree in public health education, this low seasonal influenza vaccination rate is disturbing. This study may add to the body of data demonstrating how knowledge of the vaccine does not always guarantee vaccine uptake. Results of the current study suggest that it may be beneficial to provide additional information targeted to public health students, aimed at mediating safety concerns and increasing social pressure to assist in improving vaccine acceptance and rates in this population. Maximizing seasonal influenza vaccination uptake by addressing attitudes, barriers and misperceptions may not only improve vaccination rates among public health students, but also in communities served by these future public health practitioners.

Vaccine hesitancy in the French population in 2016, and its association with vaccine uptake and perceived vaccine risk-benefit balance.

BackgroundVaccine hesitancy (VH) is prominent in France. Objectives: This study aimed to estimate the prevalence and socio-demographic correlates of VH in sub-groups of the French population and to investigate the association of VH with both vaccine uptake and perceived risk-benefit balance (RBB) for four vaccines. Methods: During the 2016 Health Barometer - a national cross-sectional telephone survey in a representative sample of the French population - parents of 1-15 year-old children, parents of 11-15 year-old girls and elderly people aged 65-75 years were asked about VH (using three questions adapted from the World Health Organization definition), vaccine uptake and perceived RBB for measles and hepatitis B (children's parents), human papillomavirus (girls' parents) and seasonal influenza (elderly people) vaccines. Results: A total of 3,938 parents including 959 girls' parents - and 2,418 elderly people were interviewed. VH prevalence estimates were 46% (95% confidence interval (CI): 44-48) among parents, 48% (95%CI: 45-51) among girls' parents and 35% (95% CI: 33-36) among elderly people, with higher estimates associated with high education level, children's age (10-15 years), and, for the elderly, poor perception of health status. VH was associated with uncertainty about and/or an unfavourable perception of vaccines' RBB for the four vaccines and with lower self-reported vaccine uptake, except for human papillomavirus vaccine in girls. Results were confirmed by multivariable analysis. Conclusion: Further research is needed to study the association between VH and vaccine uptake for other vaccines, and to design and validate measurement tools to monitor VH over time.

Differential Effects of Prior Influenza Exposures on H3N2 Cross-reactivity of Human Postvaccination Sera.

BACKGROUND: Effectiveness of seasonal influenza vaccines mainly depends upon how well vaccine strains represent circulating viruses; mismatched strains can lead to reduced protection. Humans have complex influenza exposure histories that increase with age, which may lead to different postvaccination responses to emerging influenza variants. Recent observational studies also suggest that prior vaccination may influence the performance of current seasonal vaccines. METHODS: To elucidate the effects of age and influenza preexposures on cross-reactivity of vaccination-induced human antibodies, we generated antigenic maps based on postvaccination hemagglutination inhibition titers against representative H3 variants circulating during the 2015-2016, 2014-2015, and 2012-2013 influenza seasons. RESULTS: Antigenic maps determined using sera from subjects 18-64 and ≥65 years of age correlated well with each other but poorly with those determined using sera from children. Antigenic maps derived from human postvaccination sera with H1 influenza preexposure also correlated poorly with those derived from sera with neither H1 nor type B influenza preexposure, and the correlation lessened considerably over time. In contrast, antigenic maps derived from human postvaccination sera with only type B influenza preexposure consistently showed good correlation with those derived from sera with neither H1 nor type B influenza preexposure. CONCLUSIONS: Our results suggest an age-specific difference in human postvaccination responses. Our findings also suggest that prior exposure to H1 or type B influenza may differentially affect cross-reactivity of vaccination-induced H3-specific hemagglutination inhibition antibody responses, and consequently might affect vaccine effectiveness. Our study highlights the need to study the impact of prior exposure on influenza vaccine performance.

Knowledge, awareness and practices towards seasonal influenza and its vaccine: implications for future vaccination campaigns in Jordan.

BACKGROUND: Influenza is an underestimated contributor to morbidity and mortality. Population knowledge regarding influenza and its vaccination has a key role in enhancing vaccination coverage. OBJECTIVES: This study aimed to identify the gaps of knowledge among Jordanian population towards influenza and its vaccine, and to identify the major determinants of accepting seasonal influenza vaccine in adults and children in Jordan. METHODS: This was a cross-sectional study that enrolled 941 randomly selected adults in Amman, Jordan. A four-section questionnaire was used which included questions about the sociodemographic characteristics, knowledge about influenza and the factors that affect seasonal influenza vaccine acceptance and refusal. RESULTS: Only 47.3% of the participants were considered knowledgeable. About half of the participants (51.9%) correctly identified the main influenza preventative measures. Lack of knowledge about the important role of seasonal influenza vaccine in disease prevention was observed. Low vaccination rate (20% of adults) was reported. The most critical barrier against vaccination in adults and children was the concern about the safety and the efficacy of the vaccine, while the most important predictors for future vaccination in adults and children were physician recommendation and government role. In children, the inclusion of the vaccine within the national immunization program was an important determinant of vaccine acceptance. CONCLUSION: Formulating new strategies to improve the population's level of knowledge, assuring the population about the safety and the efficacy of the vaccine and the inclusion of the vaccine within the national immunization program are the essential factors to enhance vaccination coverage in Jordan.

Sex and gender differences in adverse events following influenza and COVID-19 vaccination.

INTRODUCTION: Active and passive surveillance studies have found that a greater proportion of females report adverse events (AE) following receipt of either the COVID-19 or seasonal influenza vaccine compared to males. In a predominately young adult female population of healthcare workers, we sought to determine the intersection of biological sex and sociocultural gender differences in prospective active reporting of vaccine outcomes, which remains poorly characterized. METHODS: This cohort study enrolled Johns Hopkins Health System healthcare workers (HCWs) who were recruited from the mandatory annual fall 2019-2022 influenza vaccine and the fall 2022 COVID-19 bivalent vaccine campaigns. Vaccine recipients were enrolled the day of vaccination and AE surveys were administered two days post-vaccination for bivalent COVID-19 and influenza vaccine recipients. Data were collected regarding the presence of a series of solicited local and systemic AEs. Open-ended answers about participants' experiences with AEs also were collected for the COVID-19 vaccine recipients. RESULTS: Females were more likely to report local AEs after either influenza (OR = 2.28, p = 0.001) or COVID-19 (OR = 2.57, p = 0.008) vaccination compared to males, regardless of age or race. Males and females had comparable probabilities of reporting systemic AEs after either influenza (OR = 1.18, p = 0.552) or COVID-19 (OR = 0.96, p = 0.907) vaccination. Hormonal birth control use did not impact the rates of reported AEs following influenza vaccination among reproductive-aged female HCWs. Women reported more interruptions in their daily routine following COVID-19 vaccination than men and were more likely to seek out self-treatment. More women than men scheduled their COVID-19 vaccination before their days off in anticipation of AEs. CONCLUSIONS: Our findings highlight the need for sex- and gender-inclusive policies to inform more effective mandatory occupational health vaccination strategies. Further research is needed to evaluate the potential disruption of AEs on occupational responsibilities following mandated vaccination for healthcare workers, a predominately female population, and to more fully characterize the post-vaccination behavioral differences between men and women.

Research that addresses both the sex and gender differences of vaccine outcomes and behaviors is lacking. In this survey study of healthcare workers, comprised of mostly reproductive-aged females/women, we investigated biological sex (male/female) and gender (man/woman) differences in vaccine adverse events and outcomes following either influenza or bivalent COVID-19 vaccination.Regardless of age or race, females were more likely to report local (at injection site), but not systemic (whole body), adverse events than males, consistent across influenza and bivalent COVID-19 vaccine cohorts. Sex hormones are hypothesized to play a role in the differences in immune response following vaccination between males and females. We investigated if hormonal birth control use among females may be associated with differences in vaccine adverse events among the influenza vaccine cohort. However, there was no difference in the likelihood of reporting adverse events between birth control users and non-users. Based on open-ended responses to survey questions, women were found to report more interruptions to their daily routine than men following COVID-19 vaccination. Women were also more likely to seek out self-treatment with over-the-counter medication and intentionally schedule their vaccination around days off in anticipation of adverse events.With nearly 80% of healthcare jobs held by women, even higher for direct patient care positions like nursing, females/women may be disproportionately impacted by mandated annual vaccinations. Vaccinations are necessary for the prevention of disease transmission; however, our findings highlight a need for more equitable occupational vaccine strategies that consider both sex and gender differences.

Establishment of Reference Reagents for Single-Radial-Immunodiffusion Assay on the 2022/23 Seasonal Influenza Vaccine in Japan and Their Quality Validation.

Potency tests for influenza vaccines are currently performed using a single-radial immunodiffusion (SRID) assay, which requires a reference antigen and anti-hemagglutinin (HA) serum as reference reagents. Reagents must be newly prepared each time a strain used for vaccine production is modified. Therefore, establishing reference reagents of consistent quality is crucial for conducting vaccine potency tests accurately and precisely. Here, we established reference reagents for the SRID assay to conduct lot release tests of quadrivalent influenza vaccines in Japan during the 2022/23 influenza season. The potency of reference antigens during storage was confirmed. Furthermore, we evaluated the cross-reactivity of each antiserum raised against the HA protein of the 2 lineages of influenza B virus toward different lineages of influenza B virus antigens to select a suitable procedure for the SRID assay for accurate measurement. Finally, the intralaboratory reproducibility of the SRID assay using the established reference reagents was validated, and the SRID reagents had sufficient consistent quality, comparable to that of the reagents used for testing vaccines during previous influenza seasons. Our study contributes to the quality control of influenza vaccines.

Sustained delivery of CpG oligodeoxynucleotide by acetalated dextran microparticles augments effector response to Computationally Optimized Broadly Reactive Antigen (COBRA) influenza hemagglutinin.

A subunit or protein-based influenza vaccine can be a safer alternative to live attenuated vaccine (Flumist) and require fewer boosts than an inactivated vaccine (e.g. Fluzone). However, to form an effective subunit vaccine, an adjuvant is often needed. In this work we used electrospray to encapsulate the hydrophilic adjuvant CpG into microparticles made from the hydrophobic biodegradable polymer acetalated dextran. To understand the rate of particle degradation on CpG release, polymer that was slow (21 h at phagosomal pH 5) and fast (0.25 h at pH 5) degrading was used to encapsulate the adjuvant. The slow-degrading particles exhibited the greatest degree of innate immune stimulation of antigen-presenting cells in vitro. In mice, the broadly acting Computationally Optimized Broadly Reactive Antigen (COBRA) Y2 influenza hemagglutinin (HA) antigen was used with CpG particles, soluble CpG, or MF-59 like adjuvant Addavax. Particles and soluble CpG elicited similar induction of anti-HA antibodies and protection against lethal influenza challenge, but the sustained release particles elicited the highest levels antibody effector functions. These results demonstrate a suitable method for encapsulation of CpG oligonucleotide in a hydrophobic particle matrix, and suggest that sustained release of CpG from Ace-DEX microparticles could potentially be used to induce potent antibody effector functions.

Attitudes of parents towards influenza vaccine in the Eastern Mediterranean Region: A multilevel analysis.

BACKGROUND: Seasonal influenza vaccines (SIVs) can protect against influenza and substantially reduce the risk of influenza-related hospitalizations and fatalities in children. This study aimed to assess parental attitudes towards SIVs in the Eastern Mediterranean region (EMR). METHODS: Through an anonymous online survey conducted in 19 countries in the EMR, parents or caregivers over 18 years who had at least one child above 6 months filled out the Parent Attitudes about Childhood Vaccines questionnaire. As data had two levels; country and individual factors, we utilized multilevel binary logistic regression models. RESULTS: In total, 6992 respondents filled out the questionnaire. Of them, 47.4 % were residents of middle-income countries, 72.4 % of the mothers were between 26 and 45 years old, 56.5 % had at least a university degree, and approximately 51.6 % were unemployed. Nearly 50.8 % of the respondents were hesitant to vaccinate their children against seasonal influenza. Parental attitudes towards seasonal influenza vaccination differed significantly between countries, p < 0.001. The main predictors of parental seasonal influenza vaccine hesitancy (VH) were parents vaccination (odds ratio (OR) = 0.42, 95 % CI = 0.32-0.55, p < 0.001)), the mother's education if mother educated vs. who did not receive any education (OR ranged from 0.48 to 0.64, p < 0.05), living in low-income countries (OR = 0.52, 95 % CI = 0.35-0.77, p < 0.01), mountain residence (0.69, 95 % CI = 0.49-0.99, p < 0.05), health workers as a source of information (OR = 0.70, 95 % CI = 0.58-0.85, p < 0.001), children vaccination against COVID-19 (OR = 0.52, 95 % CI = 0.41-0.65, p < 0.001), not receiving routine vaccinations (OR = 1.93, 95 % CI = 1.09-3.44, p = 0.025), and if parents respondents could not remember whether their child had suffered from seasonal influenza in the previous year (OR = 1.57, 95 % CI = 1.33-1.84, p < 0.001). CONCLUSION: A high seasonal influenza VH rate was found in the EMR. Health authorities should implement different interventions targeting the identified modifiable risk factor to increase vaccine uptake among children, especially those at risk of complication from seasonal influenza infection.

Combining COVID-19 and seasonal influenza vaccines together to increase the acceptance of newly developed vaccines in the Eastern Mediterranean Region: a cross-sectional study.

BACKGROUND AND AIM: The World Health Organization (WHO) recommended the concomitant administration (co-administration) of inactivated seasonal influenza and coronavirus disease 2019 (COVID-19) vaccines, encouraging the practice for the 2021-2022 flu season. This study aimed to assess the acceptance of simultaneously receiving the seasonal influenza vaccine (SIV) and the COVID-19 vaccine in a single administration to reduce vaccine rejection towards the COVID-19 vaccination. METHODS: An online-based cross-section survey was conducted from 1 September to 9 November 2022, in the Eastern Mediterranean Region (EMR) through distributing the survey on different social media platforms, including Facebook, Twitter, LinkedIn and WhatsApp. We used the multi-level model to assess the variation of vaccine countries across EMR countries. RESULTS: In total, 3300 participants were included in this survey from 11 countries distributed in the EMR. More than one-third (40.7%) were aged 18-25 years, 60.6% were females, 54.0% had a university degree, 43.1% had previous COVID-19, and 41.9% had relatives or friends who died from COVID-19. In total, 43.3% accepted this combination because it is less costly (9%), safer (18%), more effective (17%), and has fewer doses (19%). Rejection of this combination was due to fear of side effects (31%), and no studies have been published on their effects (31%). There was a significant difference across countries, which accounted for 6% of the variance in the log-odds of accepting the combined vaccination. Multi-level analysis revealed that being male, African and losing a family member or friend from COVID-19 increased the acceptance of the theoretical combined vaccines. Additionally, the number of doses taken of the COVID-19 and influenza vaccines separately significantly affected the combined vaccine acceptance. However, previous COVID-19 infection and older age reduced the odds of accepting the combined vaccines. Occupational level, social status and educational level didn't significantly affect the acceptance odds. CONCLUSIONS: We can conclude that combining SIV and COVID-19 vaccines in one shot increased the overall acceptance of COVID-19 vaccines among vaccine rejectors.

Investigation of barriers to county-level seasonal influenza vaccine uptake among Medicare beneficiaries in the United States - 2018-2019 seasonal influenza season.

Introduction: As most public health decisions are made at the local level, public health interventions implemented at the local level may vary by their own unique circumstances, such as demographic composition or the availability of resources. Our objective is to estimate and characterize county-level flu vaccine uptakes among Medicare-covered adults aged ≥65 years. Methods: The flu vaccine uptake was estimated from Medicare Fee-for-Service claims for those who continuously enrolled during the 2018-2019 flu season. County-level characteristics were obtained from Centers for Disease Control and Prevention (CDC)'s Minority Health Social Vulnerability Index and Behavioral Risk Factor Surveillance System data as well as Health Resources and Services Administration's Area Health Resources File. A generalized linear regression was used to assess the relationship between selected characteristics and uptake. Results: A total of 30,265,047 beneficiaries from 3,125 counties were identified, of which 53% received a flu vaccination during the 2018-2019 flu season. For 3,006 counties with more than 500 Medicare beneficiaries, the mean county-level uptake was estimated to be 47.7%. The mean uptakes in counties designated as a health professional shortage area (HPSA) (42.6% and 48.4%, respectively), were lower than the uptakes for the non-HPSA counties (53.8%). Metro counties (53.2%) showed higher uptakes than non-metro counties (44.2%). Regression analysis results showed that the percent of working adults aged 18-64 years and female were positively associated, while the percent of Black and Hispanic adults were negatively associated. Proportions of persons with limited proficiency of English, college education or above, single parent families, multi-unit housing, and living in group quarters were positively associated and significant. Conclusions: The results confirmed that county-level flu vaccine uptakes are low, reflect persistent racial disparities in vaccine uptake, and that Medicare populations in medically underserved communities with lower socioeconomic status need more attention in improving flu vaccine uptake.