Safety of the Seasonal Influenza Vaccine in 2 Successive Pregnancies.

Importance: Although influenza vaccination has been found to be safe in pregnancy, few studies have assessed repeated influenza vaccination over successive pregnancies, including 2 vaccinations in a year, in terms of adverse perinatal outcomes. Objective: To examine the association of seasonal influenza vaccination across successive pregnancies with adverse perinatal outcomes and whether the association varies by interpregnancy interval (IPI) and vaccine type (quadrivalent or trivalent). Design, Setting, and Participants: This retrospective cohort study included individuals with at least 2 successive singleton live-birth pregnancies between January 1, 2004, and December 31, 2018. Data were collected from the Vaccine Safety Datalink, a collaboration between the Centers for Disease Control and Prevention and integrated health care organizations. Data analysis was performed between January 8, 2021, and July 17, 2024. Exposures: Influenza vaccination was identified using vaccine administration codes. The vaccinated cohort consisted of people who received influenza vaccines during the influenza season (August 1 through April 30) in 2 successive pregnancies. The comparator cohort consisted of people identified as unvaccinated during both pregnancies. Main Outcomes and Measures: Main outcomes were risk of preeclampsia or eclampsia, placental abruption, fever, preterm birth, preterm premature rupture of membranes, chorioamnionitis, and small for gestational age among individuals with and without vaccination in both pregnancies. Adjusted relative risks (RRs) from Poisson regression were used to assess the magnitude of associations. The associations with adverse outcomes by IPI and vaccine type were evaluated. Results: Of 82 055 people with 2 singleton pregnancies between 2004 and 2018, 44 879 (54.7%) had influenza vaccination in successive pregnancies. Mean (SD) age at the start of the second pregnancy was 32.2 (4.6) years for vaccinated individuals and 31.2 (5.0) years for unvaccinated individuals. Compared with individuals not vaccinated in both pregnancies, vaccination in successive pregnancies was not associated with increased risk of preeclampsia or eclampsia (adjusted RR, 1.10; 95% CI, 0.99-1.21), placental abruption (adjusted RR, 1.01; 95% CI, 0.84-1.21), fever (adjusted RR, 0.87; 95% CI, 0.47-1.59), preterm birth (adjusted RR, 0.83; 95% CI, 0.78-0.89), preterm premature rupture of membranes (RR, 1.00; 95% CI, 0.94-1.06), chorioamnionitis (adjusted RR, 1.03; 95% CI, 0.90-1.18), or small for gestational age birth (adjusted RR, 0.99; 95% CI, 0.93-1.05). IPI and vaccine type did not modify the observed associations. Conclusions and Relevance: In this large cohort study of successive pregnancies, influenza vaccination was not associated with increased risk of adverse perinatal outcomes, irrespective of IPI and vaccine type. Findings support recommendations to vaccinate pregnant people or those who might be pregnant during the influenza season.

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

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

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.

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

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

Humoral immunity and safety of respiratory virus vaccines in systemic lupus erythematosus population: a meta-analysis based on twenty-five observational studies.

BACKGROUND: Systemic lupus erythematosus (SLE), an extensive autoimmune disorder, compromises viral resistance and alters immune responses post respiratory virus vaccines. This study aims to assess immune response levels and safety in SLE patients following respiratory virus vaccines. METHODS: Extensive searches, until 1 March 2024, were conducted using PubMed, EMBASE, and Cochrane Library. Outcomes, encompassing seroconversion rate (SCR), antibody and IgG titers, neutralizing antibodies, anti-spike antibodies, anti-receptor binding domain (RBD) IgG, and adverse events, were appraised. RESULTS: Sixteen articles, comprising 25 observational studies, were included. SLE patients exhibited lower SCR (OR = 0.42, 95%CI: 0.26 to 0.69), antibody titers (SMD=-2.84, 95%CI: -3.36 to -1.61), and neutralizing antibodies (OR = 0.27, 95%CI: 0.13 to 0.56) compared to the healthy population post respiratory virus vaccines. Notably, differences were statistically insignificant for anti-RBD IgG (OR = 1.75, 95%CI: 0.10 to 29.42), IgG titers (SMD=-2.54, 95%CI: -5.57 to -0.49), anti-spike antibodies (OR = 0.35, 95%CI: 0.08 to 1.53), injection site discomfort (OR = 1.03, 95%CI: 0.52 to 2.06), fatigue (OR = 1.23, 95%CI: 0.74 to 2.03), fever (OR = 1.02, 95%CI: 0.64 to 1.63), localized reactions (OR = 0.69, 95%CI: 0.37 to 1.30), systemic reactions (OR = 1.00, 95%CI: 0.59 to 1.69), allergic reactions (OR = 5.11, 95%CI: 0.24 to 107.10), self-reported vaccination-related adverse events (OR = 1.61, 95%CI: 0.56 to 4.63), and disease flares after vaccination (OR = 1.00, 95%CI: 0.14 to 7.28). CONCLUSION: Despite the reduced immune response and host protection in SLE patients post-Corona Virus Disease 2019 (COVID-19) and influenza vaccines compared to the healthy population, safety profiles are comparable. Therefore, it is recommended that SLE patients receive COVID-19 and influenza viral vaccines to fortify their resistance.

Lot-to-lot consistency, immunogenicity and safety of a quadrivalent split virion inactivated influenza vaccine in healthy population aged 9-59 years: A randomized, double-blind, controlled, phase IV clinical trial.

OBJECTIVES: This study was to assess the lot-to-lot consistency, immunogenicity and safety of three manufacturing lots of a quadrivalent inactivated influenza vaccine (IIV4). METHODS: A randomized, double-blind, phase IV clinical trial was conducted in healthy children, adolescents and adults aged 9-59 years in Guizhou Province, China. Eligible participants were enrolled and randomized into three groups in a ratio of 1:1:1 to receive a single dose of one of three manufacturing lots of IIV4. Serum samples were collected before and 28 days after vaccination for hemagglutination inhibition (HI) antibody testing. Safety data were collected for up to 28 days after vaccination. The primary objective was to evaluate the lot-to-lot consistency of immune response as assessed by the geometric mean titer (GMT) of HI antibody at 28 days after vaccination. RESULTS: Between November 27, 2022 and December 18, 2022, 1260 eligible participants were enrolled, with similar participant demographics among groups. Immune responses after vaccination were comparable across groups, with the 95% confidence intervals (CIs) of GMT ratios for all 4 strains falling into the equivalence criterion of (0.67, 1.5). The seroconversion rates (SCRs) and seroprotection rates (SPRs) met the US Center or Biologics Evaluation and Research (CBER) criteria for all strains for each lot (lower limit of 95% CI of SCR ≥ 40% and SPR ≥ 70%). The incidences of solicited and unsolicited adverse reactions were similar among three groups, most of which (91.9%) were mild or moderate in severity. A total of 11 serious adverse events were reported during the study, and all were considered unrelated to vaccination. CONCLUSION: The three manufacturing lots of IIV4 demonstrated consistent immunogenicity. IIV4 can elicit satisfactory immune responses for all four strains and no safety concerns were identified. CLINICAL TRIAL REGISTRATION: Identifier No. NCT05512494.

Infection, vaccination and narcolepsy type 1: Evidence and potential molecular mechanisms.

NT1 is a rare, chronic and disabling neurological disease causing excessive daytime sleepiness and cataplexy. NT1 is characterized pathologically by an almost complete loss of neurons producing the hypocretin (HCRT)/orexin neuropeptides in the lateral hypothalamus. While the exact etiology of NT1 is still unknown, numerous studies have provided compelling evidence supporting its autoimmune origin. The prevailing hypothetical view on the pathogenesis of NT1 involves an immune-mediated loss of HCRT neurons that can be triggered by Pandemrix® vaccination and/or by infection in genetically susceptible patients, specifically carriers of the HLA-DQB1*06:02 MHC class II allele. The molecular mechanisms by which infection/vaccination can induce autoimmunity in the case of NT1 remain to be elucidated. In this review, evidence regarding the involvement of vaccination and infection and the potential mechanisms by which it could be linked to the pathogenesis of NT1 will be discussed in light of the existing findings in other autoimmune diseases.

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.

Background incidence rates of health outcomes of interest for COVID-19 vaccine safety monitoring in a US population: a claims database analysis.

OBJECTIVE: To evaluate background incidence rates of 59 health outcomes of interest (HOI) in a diverse population, including important subpopulations, during the pre-COVID-19 era (1 January 2017-31 December 2019) and the COVID-19 era (1 March 2020-31 December 2020), before the introduction of COVID-19 vaccines. DESIGN: Observational retrospective cohort study. Annual incidence rates and 95% confidence intervals (CIs) of HOIs were estimated for each population of interest, stratified by: age, sex, age and sex and seasonality. DATA SOURCE: Optum's de-identified Clinformatics Data Mart Database (CDM). PARTICIPANTS: Individuals from the US general population and four subgroups of interest: influenza-vaccinated, paediatric (<18 years of age), elderly (≥65 years of age) and pregnant women. RESULTS: During the COVID-19 era, the incidence of several cardiac conditions, coagulation disorders and acute liver injury increased across all populations assessed while the rates of some dermatological and neurological HOIs decreased relative to the pre-COVID-19 era. The incidence of acute respiratory distress syndrome (ARDS) varied considerably by subgroup: among the elderly, it decreased annually during the pre-COVID-19 era but peaked during the COVID-19 era; among pregnant women, it slightly increased annually during the pre-COVID-19 era and substantially increased during the COVID-19 era; among paediatrics, it decreased annually over the entire study. The incidence of the majority of HOIs increased with age, but were generally comparable between sexes with few exceptions. Cardiac, gastrointestinal, neurological and haematological HOIs, along with acute kidney injury and ARDS, were more common in males, whereas several immunological HOIs and chilblain-like lesions were more common in females. Pregnancy-related HOIs did not increase during the COVID-19 era, except for spontaneous abortions which increased annually over the entire study. CONCLUSION: These observations help contextualise fluctuations in background rates of adverse events noted during the COVID-19 era, and provide insight on how their use may impact safety surveillance for other vaccines.

ATAGI targeted review 2023: Vaccination for preventing influenza in Australia.

Abstract: Annual seasonal influenza epidemics cause substantial disease and economic burden worldwide. During the coronavirus disease 2019 (COVID-19) pandemic in 2020 and 2021, influenza activity significantly declined. However, influenza resurged in Australia following the relaxation of non-pharmaceutical interventions, with increased influenza virus circulation in early 2022 coinciding with the SARS-CoV-2 Omicron BA.2 variant wave. Together with other respiratory virus diseases, these disease impacts on the Australian population and healthcare system have re-emphasised the importance of influenza vaccination and control. We aim to provide an overview of the current seasonal influenza vaccination program in Australia and summarise evidence and considerations underpinning potential future immunisation strategies. Influenza causes disproportionately higher morbidity and mortality in young children and older adults. Other populations at elevated risk from influenza include Aboriginal and Torres Strait Islander peoples, pregnant women, and people with certain underlying medical conditions. All Australians aged ≥ 6 months are recommended to receive influenza vaccine every year. The National Immunisation Program (NIP) provides free vaccine for eligible at-risk populations. While approximately 70% of older adults had received influenza vaccine in 2022, coverage in other age groups remains suboptimal. There are several key unmet needs and challenges, but also potential strategies for enhancing the influenza vaccination program in Australia. Improved monitoring and evaluation, including the use of relevant linked datasets for such purposes, is imperative to better understand variations in coverage and vaccination impact in specific populations. Adoption of evidence-based strategies, such as culturally appropriate resources that consider the characteristics of diverse Australian populations, may also help to achieve higher vaccine coverage rates. Additionally, greater vaccine uptake across the population could be facilitated by expanding the NIP-eligible population where cost-effective, and adopting the use of more effective and different types of vaccines when available.

Stroke After Influenza Vaccines in Older Adults in the US, 2016 to 2019.

This case series investigates whether an increase in stroke risk occurred after influenza vaccination among fee-for-service Medicare beneficiaries during the influenza seasons from 2016 to 2019.

Immunogenicity and safety evaluation of a newly manufactured recombinant Baculovirus-Expressed quadrivalent influenza vaccine in adults 18 years old and Above: An Open-Label, phase III extension study.

In the face of global health threats, there is a growing demand for vaccines that can be manufactured on a large scale within compressed timeline. This study responds to this imperative by delving into the evaluation of FluGuard, a novel recombinant influenza vaccine developed by Nivad Pharmed Salamat Company in Iran. Positioned as a phase 3 extension, the research aimed to evaluate the safety and immunogenicity of FluGuard in volunteers aged 18 and above. The study was conducted as a single-center, open-label clinical trial. All eligible volunteers received FluGuard (2021-2022 Formula) on day 0. Safety assessments occurred at days 1, 4, 7, 14, 28 and 42 post-vaccination. Immunogenicity was measured through seroconversion, seroprotection, and geometric mean titer fold increase in subgroups of 250 volunteers. Among the 4,260 volunteers were screened and assessed for eligibility, 1000 were enrolled. At day 28 post-vaccination, seroconversion rates for A/H1N1, A/H3N2, B/Yamagata, B/Victoria were 53.4 % [95 %CI: 46.7-60], 57.7 % [95 %CI: 51.1-64.3], 54.3 % [95 %CI: 47.7-60.9], and 36.2 % [95 %CI: 29.8-42.6], respectively in volunteers 18 years and above. The most common solicited adverse events were pain at the injection site, malaise, and headache. No suspected unexpected adverse events and adverse events of special interest occurred during the study period. Our findings suggested that FluGuard® exhibits a desirable safety profile and provides sufficient immunogenicity against influenza virus types A and B. However, extended studies are warranted to assess the long-term protective efficacy. Trial Registration: The study protocol was accepted by Iranian registry of clinical trial; https://www.irct.ir; IRCT20201104049265N2.

Uptake, safety and effectiveness of inactivated influenza vaccine in inflammatory bowel disease: a UK-wide study.

OBJECTIVE: To investigate (1) the UK-wide inactivated influenza vaccine (IIV) uptake in adults with inflammatory bowel disease (IBD), (2) the association between vaccination against influenza and IBD flare and (3) the effectiveness of IIV in preventing morbidity and mortality. DESIGN: Data for adults with IBD diagnosed before the 1 September 2018 were extracted from the Clinical Practice Research Datalink Gold. We calculated the proportion of people vaccinated against seasonal influenza in the 2018-2019 influenza cycle. To investigate vaccine effectiveness, we calculated the propensity score (PS) for vaccination and conducted Cox proportional hazard regression with inverse-probability treatment weighting on PS. We employed self-controlled case series analysis to investigate the association between vaccination and IBD flare. RESULTS: Data for 13 631 people with IBD (50.4% male, mean age 52.9 years) were included. Fifty percent were vaccinated during the influenza cycle, while 32.1% were vaccinated on time, that is, before the seasonal influenza virus circulated in the community. IIV was associated with reduced all-cause mortality (aHR (95% CI): 0.73 (0.55,0.97) but not hospitalisation for pneumonia (aHR (95% CI) 0.52 (0.20-1.37), including in the influenza active period (aHR (95% CI) 0.48 (0.18-1.27)). Administration of the IIV was not associated with IBD flare. CONCLUSION: The uptake of influenza vaccine was low in people with IBD, and the majority were not vaccinated before influenza virus circulated in the community. Vaccination with the IIV was not associated with IBD flare. These findings add to the evidence to promote vaccination against influenza in people with IBD.

Assessment of the herpes zoster risk among renal transplant recipients administered the influenza vaccine.

BACKGROUND: Reactivation of the latent varicella-zoster virus can cause herpes zoster (HZ) infection, and renal transplant recipients undergoing immunosuppressive therapy are particularly susceptible to this condition. This study aims to evaluate the potential increase in HZ incidence following influenza vaccination among this specific patient population. METHODS: This study was a population-based, retrospective, self-controlled case series. Data were retrieved from Taiwan's National Health Insurance Research Database spanning the years 2008 to 2017. Patients diagnosed with HZ within a 6-month period before and after receiving the influenza vaccine were eligible for inclusion. Two distinct time intervals were defined for analysis: the initial 15 days and 30 days following vaccination were categorized as risk intervals, while all other periods served as control intervals. Incidence rate ratios (IRRs) were computed to compare HZ incidence during the risk intervals with that during the control intervals. RESULTS: This study encompassed a cohort of 4,222 renal transplant recipients who had received the influenza vaccine. Among this group, 67 recipients were subsequently diagnosed with HZ. The IRR during both the initial 15 days (IRR = 0.63; 95 % CI, 0.23-1.89) and the first 30 days (IRR = 1.50; 95 % CI, 0.71-3.16) following influenza vaccination did not demonstrate a statistically significant increase when compared to the post-exposure observation times. Comparable results were also observed when comparing these IRR values to the pre-exposure observation times. The subgroup analysis, stratified by age, sex, and underlying medical conditions (including cancer and autoimmune diseases), revealed that the IRRs did not exhibit statistically significant differences. CONCLUSIONS: No significant association between the influenza vaccine and an elevated risk of HZ was detected. The administration of annual influenza vaccines appears to be a reasonable practice for renal transplant recipients.

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.

An Unexpected Post-Egg-Free Influenza Vaccine Granulomatous Reaction.

ABSTRACT: A 53-year-old woman presented with a pruritic plaque on the left upper arm that appeared following an egg-free flu vaccine due to a history of reaction to the standard vaccine. The affected area enlarged over a several month period immediately following vaccine administration. Physical examination revealed an 8 × 4 cm coalescent pink plaque on the left upper arm. A shave biopsy of the lesion showed dermal "naked" granulomas, or granulomas with sparse lymphocytic infiltrate at the margins, as typically seen in sarcoidosis. No foreign material was seen in the granulomatous reaction, including with polarization. Special stains, including acid fast bacilli, Grocott methenamine silver, periodic acid-Schiff, and Gram, were negative for organisms. The diagnosis of granulomatous dermatitis was made. Subsequent imaging demonstrated no findings suggestive of sarcoidosis. While vaccine-associated hypersensitivity reactions occur frequently, these reactions are typically due to individual vaccine components, such as egg protein, and do not normally result in the formulation of granulomas. Vaccination-induced granulomas are more often associated with the use of aluminum as an adjuvant; however, this is not present in the egg-free influenza vaccine. Thus, a granulomatous reaction to the egg-free influenza vaccine is very unusual and, to our knowledge, not previously reported.

Phase 1, randomized, rater and participant blinded placebo-controlled study of the safety, reactogenicity, tolerability and immunogenicity of H1N1 influenza vaccine delivered by VX-103 (a MIMIX microneedle patch [MAP] system) in healthy adults.

BACKGROUND: The MIMIX platform is a novel microneedle array patch (MAP) characterized by slowly dissolving microneedle tips that deploy into the dermis following patch application. We describe safety, reactogenicity, tolerability and immunogenicity for MIMIX MAP vaccination against influenza. METHODOLOGY: The trial was a Phase 1, exploratory, first-in-human, parallel randomized, rater, participant, study analyst-blinded, placebo-controlled study in Canada. Forty-five healthy participants (18 to 39 years of age, inclusive) were randomized in a 1:1:1 ratio to receive either 15 µg or 7.5 µg of an H1N1 influenza vaccine, or placebo delivered via MIMIX MAP to the volar forearm. A statistician used a computer program to create a randomization scheme with a block size of 3. Post-treatment follow-up was approximately 180 days. Primary safety outcomes included the incidence of study product related serious adverse events and unsolicited events within 180 days, solicited application site and systemic reactogenicity through 7 days after administration and solicited application site erythema and/or pigmentation 14, 28, 56 and 180 days after administration. Immunogenicity outcomes included antibody titers and percentage of seroconversion (SCR) and seroprotection (SPR) rates determined by the hemagglutination inhibition (HAI) assay. Exploratory outcomes included virus microneutralization (MN) titers, durability and breadth of the immune response. The trial was registered with ClinicalTrials.gov, number NCT06125717. FINDINGS: Between July 7, 2022 and March 13, 2023 45 participants were randomized to a treatment group. One participant was lost to follow up in the 15 µg group and 1 participant withdrew from the 7.5 µg dose group. Safety analyses included n = 15 per group, immunogenicity analyses included n = 14 for the 15 µg and 7.5 µg treatment groups and n = 15 for the placebo group. No SAEs were reported in any of the treatment groups. All treatment groups reported solicited local events within 7 days after vaccination, with mild (Grade 1) erythema being the most frequent symptom reported. Other local symptoms reported included mostly mild (Grade 1) induration/swelling, itching, pigmentation, skin flaking, and tenderness. Within 7 days after vaccination, 2 participants (4.4%) reported moderate (Grade 2) erythema, 1 participant (2.2%) reported moderate (Grade 2) induration/swelling, and 1 participant (2.2%) reported moderate (Grade 2) itching. There was an overall reduction in erythema and pigmentation reported on Days 15, 29, 57, and 180 among all treatment groups. Systemic symptoms reported within 7 days after vaccination, included mild (Grade 1) fatigue reported among all treatment groups, and mild (Grade 1) headache reported by 1 participant in the 7.5 µg treatment group. No study drug related severe symptoms were reported in the study. Group mean fold rises in HAI titers ranged between 8.7 and 12-fold, SCRs were >76% and SPRs were >92% for both VX-103 dose groups thereby fulfilling serological criteria established by the EMA and FDA for seasonal influenza vaccines. Longitudinal assessments demonstrate persistence of the immune response through at least Day 180. CONCLUSIONS: The MIMIX MAP platform is safe, well tolerated and elicits robust antibody responses.

Global estimates on the reports of vaccine-associated myocarditis and pericarditis from 1969 to 2023: Findings with critical reanalysis from the WHO pharmacovigilance database.

Due to the limitation of previous studies examining adverse reports of myocarditis and pericarditis associated with vaccines other than the COVID-19 vaccine, there are challenges in establishing a comprehensive understanding of vaccine safety on a global scale. Hence, the objective of this study was to examine the worldwide burden of vaccine-associated pericarditis and myocarditis and the vaccines associated with these indications. This study utilized the World Health Organization international pharmacovigilance database, from which records of vaccine-associated pericarditis and myocarditis between 1969 and 2023 were extracted (over 130 million reports). We calculated global reporting counts, reported odds ratios (RORs), and information components (ICs) to discern the association between 19 vaccines and the occurrence of pericarditis and myocarditis across 156 countries and territories. We identified 49 096 reports (male, n = 30 013) of vaccine-associated pericarditis and myocarditis among 73 590 reports of all-cause pericarditis and myocarditis. There has been a significant increase in reports of vaccine-related cardiac adverse events over time, with a noteworthy surge observed after 2020, attributed to cases of pericarditis associated with COVID-19 mRNA vaccines. Smallpox vaccines were associated with most pericarditis and myocarditis reports (ROR: 73.68 [95% CI, 67.79-80.10]; IC [IC0.25]: 6.05 [5.91]), followed by COVID-19 mRNA vaccine (37.77 [37.00-38.56]; 3.07 [3.05]), anthrax vaccine (25.54 [22.37-29.16]; 4.58 [4.35]), typhoid vaccine (6.17 [5.16-7.38]; 2.59 [2.29]), encephalitis vaccine (2.00 [1.48-2.71]; 0.99 [0.47]), influenza vaccine (1.87 [1.71-2.04]; 0.90 [0.75]), and Ad5-vectored COVID-19 vaccine (1.40 [1.34-1.46]; 0.46 [0.39]). Concerning age and sex-specific risks, reports of vaccine-associated pericarditis and myocarditis were more prevalent among males and in older age groups. The age group between 12 and 17 years exhibited significant sex disproportion. Most of these adverse events had a short time to onset (median time: 1 day) and fatality rate was 0.44%. Our analysis of global data revealed an increase in pericarditis and myocarditis reports associated with vaccines, particularly live vaccines like smallpox and anthrax, notably in young males. While these adverse events are generally rare and mild, caution is warranted, especially for healthcare workers, due to potential myocardial injury-related in-hospital mortality. Further study with validated reporting is crucial to enhance accuracy in evaluating the correlation between vaccines and cardiac conditions for preventive measures.