To explore the immunogencity and safety of HDCV using a six-dose Essen regimen in human immunodeficiency virus (HIV) infected patients. We conducted a single-arm pilot study by simulating post-exposure prophylaxis (PEP) in HIV-infected patients. All patients were administrated with HDCV using a 6-dose Essen regimen (consisting of 2 doses on day 0, and 4 doses each on day 3, 7, 14, and 28). Rabies virus-neutralizing antibody (RVNA) titers were detected on day 0, 7, 14, and 45, separately. The adverse reactions were also observed. In addition, we divided the patients with the baseline CD4+ T-cell counts of 500 cells/μL to examine the correlation between primary CD4+ T-cell counts and RVNA titers among HIV patients. Thirty patients included in the study were mostly male (96.7%), with a median age of 30.5 years and stable antiretroviral therapy (ART) treatment. Patients had RVNA titers of 0.84 IU/mL on day 7, 9.94 IU/mL on day 14, and 4.02 IU/mL on day 45 after vaccination, with significant differences between day 7 and day 14. The seroconversion rate reached 100% on day 14. Only three patients developed transient adverse reactions（including fever and redness, swelling, pain, and induration at the injection site）. There was no significant difference in antibody titers and safety profile between patients with CD4+T-cell counts below and above 500 cells/μL. A favorable immune response was achieved in HIV patients using the six-dose Essen regimen with HDCV. The safety profile of HDCV is satisfactory, with no major adverse events.

The nervous system (NS) experiences morphological and functional changes during the aging process, where low-grade chronic inflammation, oxidative stress and senescence are key regulators. Sulforaphane (SFN) is an isothiocyanate that activates redox response and inhibits the inflammatory process, which could modify the pro-inflammatory components of senescent cells secretory phenotype (SASP). Here we aimed to determine if SFN long-term treatment was able to prevent age-associated damage in the NS of adult and old females and males Wistar rats. We evaluated cytokines and chemokines profile, senescent cells markers, and memory parameters of adult (15 m.o.) and old (21 m.o.) rats after three months of SFN treatment. Young rats (4 m.o.) were used as age controls. Differences between sexes were observed in the inflammatory profile. Our results showed that SFN-treatment diminished proinflammatory molecules, senescence markers and senescent cells number in brain cortex and hippocampus from males and females' adult rats, but no effects were observed in both sexes old groups compared with the same age control groups. SFN-dependent reduction in inflammatory and senescence parameters resulted in better scores in Barnes Maze Trial memory test when compared with same age non-treated group. Interestingly, adult females showed higher levels of proinflammatory cytokines and chemokines than adult males, which were prevented by SFN-treatment. No effects of SFN were observed in memory of old-treated groups.

Pneumococcal infections pose a significant health problem in individuals with comorbid conditions such as Type 2 diabetes mellitus. Although pneumococcal vaccines are recommended in individuals with type 2 diabetes, there is a lack of data on the immunogenicity of pneumococcal vaccines in the type 2 diabetes population. This pilot study was therefore developed to determine if the humoral immune response to the 10-valent pneumococcal conjugate vaccine (PCV10) in those with and without type 2 diabetes is comparable.

A total of 40 (24 with type 2 diabetes and 16 without type 2 diabetes) adults were immunized with PCV10. WHO reference ELISA and multiplexed opsonophagocytic killing assay (MOPA) were used to measure the concentration and functionality of serotype-specific IgG at baseline and 14 days, 1 month, and 8 months post-vaccination.

The geometric mean IgG concentrations and opsonic titers increased significantly in post-immunization (T1-14 days, T2-1 month, and T3-8 month) serum samples compared to baseline (T0) in individuals with and without type 2 diabetes. In both groups, the highest post-immunization IgG concentrations were measured for serotype 19F at T2. Individuals with type 2 diabetes showed significantly lower IgG concentrations and opsonic titers for serotype 19F and 9V post-immunization compared to age and sex-matched non-diabetes individuals. Serotype-specific IgG concentrations declined rapidly in those with type 2 diabetes at 8 months post-immunization. Obese diabetes individuals had lower IgG concentrations compared to non-Obese individuals with type 2 diabetes.

Individuals with type 2 diabetes demonstrated a significant protective humoral immune response to the 10-valent pneumococcal conjugate vaccine (PCV10); however, the response was comparatively less robust and declined faster in those with type 2 diabetes compared to age and sex-matched non-diabetes controls.

When considering the acute effects of different modalities of endurance training on cellular immune components, the matching of duration and mean intensity and the consideration of sex-dependent differences have received less attention so far. The aim of the study was to compare the effects of interval running (IR) vs. continuous running (CR) on circulating immune cells and cellular immune inflammation markers. Additionally, we analyze sex-dependent differences in these effects. In a cross-over study design, 24 recreational runners completed a mean intensity and duration-matched session of IR and CR. Blood samples were taken immediately before, after, and 1 h after exercise cessation for cell counts and cortisol level quantification. Neutrophil counts showed a sustained increase after both exercise modalities with significantly greater values after IR compared to CR at 1 h after exercise and greater increases in females. Neutrophil-to-lymphocyte ratio and systemic immune-inflammation index increased 1 h after exercise with significantly higher values after IR compared to CR with greater values in females. Platelet-to-lymphocyte ratio decreased in both immediately after IR and 1 h after exercise in both sexes and modalities. The cortisol level shows a lower value immediately after CR compared to IR with no sex-dependent differences. The IR protocol induces greater immune cell mobilizations in comparison to CR, which is primarily based on a systemic increase in neutrophil counts. Neutrophil-to-lymphocyte ratio and systemic immune-inflammation index are suitable to distinguish this effect between training modalities. Sex-dependent differences confirm that biological sex influences the immune cells response to acute exercise. Protocol registration: German Clinical Trials Register, DRKS00017686, Date of registration: 11.02.2020.

Human papillomavirus (HPV)-associated cancers are vaccine preventable. In 2016, the previously recommended three-dose HPV vaccination series was changed to a two-dose series and nine-valent HPV vaccine (9vHPV) became the only HPV vaccine available in the United States. Data on longer-term duration of antibodies following a 9vHPV two-dose series are limited. We evaluated the immunogenicity and duration of antibodies up to three years after vaccination with a two-dose series of 9vHPV in a cohort of Alaska Native children.

We enrolled Alaska Native children aged 9-14 years who received 9vHPV in Anchorage, Alaska during 2017-2018. We collected sera at six months after dose one and at one month, one year, and three years after dose two to measure type-specific immunoglobulin G (IgG) concentrations for the 9vHPV types (HPV6/11/16/18/31/33/45/52/58). Aggregate type-specific IgG concentrations were reported as geometric mean concentrations (GMC).

A total of 227 children completed the two-dose series of 9vHPV and provided ≥ 1 blood sample. The median age at enrollment was 11.0 years (range: 9.0-14.6) and was similar between males and females (p = 0.11). At one month after dose two, all 197 participants with available serum were seropositive for all 9vHPV types. Among 145 participants who had a specimen available at three years after dose two, 134 (92%) remained seropositive for all 9vHPV types. GMC peaked for all types at one month post dose two and remained higher at three years post dose two compared to six months post dose one.

We found high immunogenicity and antibody persistence after a two-dose series of 9vHPV in this cohort of Alaska Native children. Further follow-up will determine duration of antibody detection in this cohort.

This study examines covid-19 vaccine coverage among adults and describes self-reported post-vaccine adverse events and associated risk factors in Mbuji-Mayi.

A cross-sectional study was conducted, with the study population including adults (18 years and older) who received at least one dose of vaccine in the Bonzola health zone in Mbuji-Mayi between 27 March 2023 and 27 June 2023. The Pearson chi-square test (χ2) and multinomial logistic regression analyses were performed using IBM SPSS Statistics 29 and Epi Info 7.2.4.0 software.

A survey of 422 people showed that only 164 (38.86%) had been vaccinated, and 83.54% of these people had had bad reactions to the vaccine. Respondents were mainly men (50.4%) aged between 18 and 25 (52.44%). The most common vaccine was the Johnson & Johnson vaccine (43.8%), followed by the AstraZeneca vaccine (40.1%). The most frequent side effects after vaccination were moderate (fever and vomiting) and least frequent (cough and headache). The results of the multivariate analysis showed that age and sex (respectively 2,946 times (95% CI: 2,946-197,279), 10,019 times (95% CI: 1,214-82,660) and 55,489 times (95% CI: 5,742-536,248) higher than that of men) were associated with the occurrence of self-reported post-vaccination side effects, as well as fever, headache and cough.

In view of the sub-optimal rate of vaccination coverage, it is evident that the prevailing circumstances have not been immune to the occurrence of adverse events reported by stakeholders following vaccination against the new coronavirus (Covid-19). This underscores the necessity for rigorous safety monitoring. The dissemination of these findings, in conjunction with the results of vaccine clinical trials, has the potential to contribute to the reduction of mistrust, which is a persistent challenge in the context of vaccine hesitancy.

Early identification of patients living with cancer at higher risk of death from an infection is critical in infection mortality prevention. We characterize patients living with cancer at the highest risk of dying from an infection.

7,529,481 US cancer survivors (1992 to 2015) were extracted from the Surveillance, Epidemiology, and End Results (SEER) database. Standardized mortality ratios (SMRs) and 95% CIs were calculated. Fine-gray survival analysis was performed to calculate hazard ratios by adjusting for the effects of competing risks (eg, deaths due to causes other than infection).

Among 7,529,481 patients living with cancer (1992 to 2015), 101,167 (1.3%) died of infection. The rate of infection-specific mortality was 27.19/10,000 person-years, with an SMR of 3.29 (95% CI: 3.26-3.32, P<0.001). Patients who were older, male, black, and unmarried were at a greater risk of fatal infection. Overall, the risk of infection-specific mortality for patients living with cancer is greatest 1 year after diagnosis compared with the general population (SMR: 8.68, 95% CI: 8.53-8.84; P<0.0001), and this risk decreases with follow-up time (SMR at >10 y after diagnosis: 2.93, 95% CI: 2.87-3.00; P<0.0001). Among patients with Hodgkin Lymphoma, Non-Hodgkin Lymphoma, and Kaposi Sarcoma, 9.2%, 11.5%, and 82.2% of all deaths within the first year after cancer diagnosis occurred due to acute infectious disease. In contrast, for patients with liver cancer, the relative percentage of infection-specific mortality increases with follow-up time from 3.5% at <1 year after cancer diagnosis and 10.4% at 10+ years of follow-up.

The results of this study characterize infection mortality in patients living with cancer, which can guide more targeted research and interventions in this population.

Realizing the potential of HIV prevention options requires understanding product tolerability across diverse groups vulnerable to HIV acquisition. Gender minority (GM) individuals are understudied in clinical trials.

HVTN 704/HIV Prevention Trials Network 085, a phase 2b randomized HIV prevention trial, enrolled MSM and transgender participants from Brazil, Peru, Switzerland, and the United States to receive an infusion every 8 weeks (10 total) of VRC01 30 mg/kg, VRC01 10 mg/kg, or placebo. Solicited adverse events (AEs) were recorded for 3 days after each infusion.

Gender was defined by self-report and sex assigned-at-birth. Multivariate mixed logistic models were used to estimate the association between gender (cisgender men [CM] vs. GM participants [transgender women, transgender men, or another gender]) and solicited AE frequency and severity.

GM participants reported more solicited AEs than CM among all participants (adjusted OR 1.59, 95% CI: 1.20 to 2.10, P = 0.001) and among placebo recipients (1.72, 1.05 to 2.81, P = 0.031). The severity of solicited AEs (occurrence of grade 2 and higher event) did not significantly differ overall (1.83, 0.79 to 4.20, P = 0.174) or among placebo recipients (3.05, 0.76 to 12.32, P = 0.112). Grade 2 events were reported after 1% and 2% of total infusions among CM and GM participants, respectively. Grade 3-4 events were rare overall (<0.1%). Completion of 10 infusions was high (78.6%) and slightly higher in CM (79.2%) than GM participants (73%).

This is the first report of associations between gender and solicited AEs after monoclonal antibody infusion. GM participants reported more events; severity was low. HIV prevention trials must engage and support GM individuals to best evaluate tolerability of novel agents.

Estrogen deficiency in postmenopausal women is accompanied by immune status alterations, leading to a chronic low-grade inflammatory phenotype. Immediate rabies postexposure prophylaxis (PEP) following a transdermal bite or scratch from a rabies-infected animal is urgently needed. However, whether immune alterations in postmenopausal women influence the reaction to rabies vaccination remains unclear. Bilateral ovariectomized (OVX) and Sham mice were immunized with modified live vaccine RABV LBNSE. LBNSE immunization had no obvious pathological effect on the mice in either group and effectively protected all mice from RABV attack. Although 100% protection was found, the reduction rate of viral neutralizing antibody titers in the LBNSE-OVX mice was greater than that in the LBNSE-Sham mice. LBNSE immunization recruited/activated fewer dendritic cells (DCs) and B cells in the lymph nodes, while more B cells were detected in the blood of LBNSE-OVX mice than in that of LBNSE-Sham mice. Th1 and Th2 immune responses are both rapidly induced in LBNSE-OVX-subjected mice and are inclined toward a Th2-biased immune response. LBNSE immunization in OVX mice elicited similar amounts of RABV-specific CD4+ and CD8+ T cells as those in Sham mice. Our data revealed that the protective efficacy of rabies vaccination was slightly decreased by estrogen deficiency and that DC and B lymphocyte recruitment/activation and Th-mediated responses in splenocytes were partly altered; however, rabies vaccination offered sufficient protection against RABV within the observation period, helping alleviate anxiety related to rabies virus exposure after menopause. Additional measures might be helpful to improve long-term effective protection in postmenopausal women.IMPORTANCEMenopause has a distinct effect on the decrease in the female immune system, and whether protection efficacy after rabies vaccination in postmenopausal women is influenced requires evaluation. Our findings demonstrated that although viral neutralizing antibody (VNA) titers in the LBNSE-OVX mice were similar to those in the LBNSE-Sham mice, VNAs declined faster than those in the LBNSE-Sham mice within the observation period. Fewer dendritic cells in the lymph nodes were recruited/activated in LBNSE-OVX mice than in LBNSE-Sham mice, whereas B cells in the lymph nodes and peripheral blood exhibited the opposite tendency. Th2-biased immune responses were induced in LBNSE-OVX mice, and no significant changes were observed in RABV-specific CD4+ or CD8+ T cells. These results provide evidence that rabies vaccination could provide effective protection for postmenopausal women within the observation period, but other measures might be needed to improve protection, which is beneficial for alleviating anxiety of menopausal women when facing rabies immunization.

The live-attenuated yellow fever 17D (YF17D) vaccine is a model of acute viral infection that induces long-lasting protective immunity. Among immunocompetent adults, responses to YF17D vary significantly. To understand the sources of this variability, we investigate the influence of sex, age, human leukocyte antigen (HLA) type, and 20 prior infections on basal immune parameters and the cellular and antibody response to YF17D in 250 healthy young individuals. Multivariate regression found that sex and cytomegalovirus (CMV) infection significantly contribute to baseline immune variation but do not affect vaccine responses except for reduced YF17D-specific CD8+ frequencies in CMV-infected males. However, the abundance at baseline of non-specific cytokine-expressing T helper cells in circulation is associated with stronger vaccine responses, a state that smoking favors. Additionally, an elevated baseline level of interferon-stimulated CXCL10 is linked to poorer vaccination outcomes. Altogether, YF17D reactivity is conditioned by the baseline immune status independent of sex and CMV-related variations.

Adverse events following immunizations (AEFIs) with recombinant zoster vaccine (RZV) are underexplored in fragile populations. This study aims to assess incidence, duration, and characteristics of AEFIs, focusing on the impact of sex, age, and prior Herpes Zoster (HZ) infection in a frail population, including solid organ transplant recipients. We conducted an observational study on patients receiving RZV, and AEFIs were classified as local or systemic and analyzed for incidence, duration, and patterns across groups. We showed that females had a higher incidence of AEFIs (p = 0.02), both local and systemic symptoms, such as swelling +/- redness at the site of injection and fatigue, after the first and second doses. Younger adults experienced more systemic reactions, while older adults reported more local events (e.g., redness and swelling, p = 0.01). Moreover, patients with previous HZ infection exhibited a higher incidence of AEFIs after the second dose (68% vs. 38%, p = 0.001). In conclusion, sex, age, and clinical history significantly influenced AEFI incidence and manifestations. Therefore, it is important to personalize vaccination strategies in frail populations, by tailored administration and monitoring plans, especially in females and individuals with prior HZ infection, to improve vaccine safety and patient outcomes.

BackgroundRespiratory syncytial virus (RSV) causes substantial morbidity in infants < 1 year. In October 2023, Spain recommended the monoclonal antibody nirsevimab to all children born since 1 April 2023, at birth or as catch-up if born before October 2023.AimWe estimated nirsevimab effectiveness in preventing RSV hospitalisations during the 2023/24 season.MethodsWe conducted a nationwide population-based matched case-control study. Cases were children hospitalised for lower respiratory tract infection who were RSV PCR-positive. For each case, we selected four population density controls born in the same province and date (±2 days). We defined at-birth immunisation as receiving nirsevimab during the first 2 weeks of life, and catch-up immunisation within 30 days from campaign onset. Causal intention-to-treat (ITT) and per-protocol (PP) effectiveness was estimated using inverse-probability-of-immunisation weighted conditional logistic regression.ResultsWe included 406 cases and 1,623 controls in catch-up and 546 cases and 2,182 controls in at-birth immunisation studies. Effectiveness in preventing RSV hospitalisations for catch-up immunisation was 71% (95% confidence interval (CI): 65-76) by ITT and 80% (95% CI: 75-84) PP. Effectiveness for at-birth immunisation was 78% (95% CI: 73-82) by ITT and 83% (95% CI: 79-87) PP. Effectiveness was similar for ICU admission, need of mechanical ventilation, and RSV viral subgroups A and B. Children born pre-term or with birthweight < 2,500 g showed lower PP effectiveness of 60-70%.ConclusionsPopulation-level nirsevimab immunoprophylaxis in children in their first RSV season was very effective in preventing RSV hospitalisations, ICU admission and mechanical ventilation, with reduced but still high effectiveness for pre-term and low-birthweight children.

This study investigates adverse events following vaccination in patients with four neurodegenerative diseases: Amyotrophic Lateral Sclerosis (ALS), Alzheimer's disease, Multiple Sclerosis (MS), and Parkinson's disease. We applied advanced data processing techniques to analyze symptom patterns and severity scores across these disease groups. Patients were identified through filtering, and symptom clusters were extracted to group similar symptoms into distinct clusters, and severity scores were computed based on hospitalization and death reports. A chi-squared test was performed to assess the statistical significance of adverse event distributions among the diseases for different vaccines. The results reveal that ALS patients exhibit severe respiratory symptoms post-vaccination, while Alzheimer's patients report significant respiratory and gastrointestinal issues. MS patients commonly experience general symptoms such as fatigue, while Parkinson's patients face exacerbated motor symptoms. Notably, our analysis showed no significant difference in adverse event reporting rates between COVID-19 and pneumococcal vaccines across these disease groups. This research provides new insights into disease-specific responses to vaccines, emphasizing the importance of personalized monitoring and treatment strategies to mitigate risks and improve clinical outcomes in these vulnerable populations.

Axial spondyloarthritis (axSpA) is a rather prevalent chronic inflammatory rheumatic disease that affects already relatively young patients. It has been known better since the end of the nineteenth century but quite a lot has been learned since the early 60ies when the first classification (diagnostic) criteria for ankylosing spondylitis (AS) were agreed on. I have been part of many developments in the last 30 years, and I'm happy to have been able to contribute to the scientific progress in terms of diagnosis, imaging, pathophysiology and therapy. When I was asked to write a manuscript about the SpA concept I felt honored. Thus, the purpose of this extensive review was, on the one hand, to describe the history of AS and axSpA, and on the other hand, to reason about the concept and the gestalt of axSpA, and finally to deliver some ideas what future researchers could possibly do to further study the disease.

The last 3 decades were full of innovations for both, classification and treatment of axSpA which also helped us to learn about the pathophysiology. Thus, TNFa, IL-17, IL-23 and Janus kinase are established targets to reduce inflammation. IL-17 and IL-23 are very special in that regard because they both work for psoriasis but only anti-IL-17 agents which don't work in IBD are approved for axSpA, while IL 23 inhibitors are approved for both, psoriasis and IBD, but they don't work in axSpA. New imaging techniques such as low dose CT and synthetic MRI are likely to improve the detection of both active and structural lesions of axSpA. This manuscript tries to describe the most important findings about axSpA. The main aim of research remains to discover the pathophysiology and to further improve treatment options in order to reduce and abolish inflammation and prevent new bone formation to increase the quality of life of our patients. The differences between male and female disease and the role of the immune system in axSpA are now the main challenges, and the role of special T-cell receptors seem to deserve special interest.

 The psychological approach can provide valuable insights into vaccination behaviour, especially in high-risk contexts. It offers new perspectives for effective interventions to improve vaccination behaviour.

 To investigate key factors influencing stress related to vaccination in emergency situations among healthcare professionals.

 Eastern region of Morocco.

 We conducted a descriptive and analytical cross-sectional study involving 221 healthcare professionals in the Eastern region of Morocco. A snowball sampling method was used to select the participants who were administered a questionnaire. Logistic regression analysis was performed with p  0.05 being the level of statistical significance.

 The participants had a median age of 25.5 years (30-34.5) and were predominantly females (68.3%). Vaccination coverage stood at 84.6%, with a positive perception of 77.8%. The analysis of the Perceived Stress Scale (PSS) revealed that 51.6% (n = 114) of healthcare professionals experienced stress towards vaccination. Females were almost two times more susceptible to experiencing vaccination stress (p = 0.03). Furthermore, the analysis showed that vaccination profile (p = 0.02), accepting the vaccine for any reason other than its accessibility (p = 0.03) and having a previous coronavirus disease 2019 infection (p = 0.03), were significantly associated with stress. In contrast, healthcare professionals based at the university hospital had a significantly lower stress level (p = 0.01).

 Moroccan healthcare professionals exhibited high vaccine acceptance and positive perceptions, particularly among vaccinated individuals despite notable stress around immunisation.Contribution: These insights can guide governments and policymakers in developing strategies to enhance healthcare workers' awareness and understanding of vaccination.

Emerging evidence suggests that classical psychedelics possess immunomodulatory and anti-inflammatory properties; however, these effects are yet to be well-established. This systematic review aims to provide a timely and comprehensive overview of the immunomodulatory effects of classical psychedelics in preclinical studies. A systematic search was conducted on six databases, including CINAHL, EMBASE, MEDLINE, PsychINFO, Scopus, and Web of Science. Eligible studies targeting classical psychedelics for evaluation of their effects on inflammatory markers and immunomodulation have been included for analysis. Data was extracted from 40 out of 2822 eligible articles, and their risk of bias was assessed using the Systematic Review Center for Laboratory Animal Experimentation (SYRCLE) tool and Quality Assessment Tool for In Vitro Studies (QUIN). Studies examined 2,5-dimethoxy-4-iodoamphetamine (DOI; n = 18); psilocybin (4-PO-DMT; n = 9); N,N-dimethyltryptamine (DMT; n = 8); lysergic acid diethylamide (LSD; n = 6); 5-methoxy-N,N-dimethyltryptamine (5-MeO-DMT; n = 3); psilocin (4-HO-DMT; n = 3); and mescaline (n = 2). In 36 studies where inflammatory cytokine levels were measured following psychedelic administration, a decrease in at least one inflammatory cytokine was observed in 29 studies. Immune cell activity was assessed in 10 studies and findings were mixed, with an equal number of studies (n = 5 out of 10) reporting either an increase or decrease in immune cell activity. Classical psychedelics were found to alleviate pre-existing inflammation but promote inflammation when administered under normal physiological conditions. This information is anticipated to inform future clinical trials, exploring classical psychedelics' potential to alleviate inflammation in various pathologies.

Allergies are closely associated with sex-related hormonal variations that influence immune function, leading to distinct symptom profiles. Similar sex-based differences are observed in other immune disorders, such as autoimmune diseases. In allergies, women exhibit a higher prevalence of atopic conditions, such as allergic asthma and eczema, in comparison to men. However, age-related changes play a significant role because men have a higher incidence of allergies until puberty, and then comes a switch ratio of prevalence and severity in women. Investigations into the mechanisms of how the hormones influence the development of these diseases are crucial to understanding the molecular, cellular, and pathological aspects. Sex hormones control the reproductive system and have several immuno-modulatory effects affecting immune cells, including T and B cell development, antibody production, lymphoid organ size, and lymphocyte death. Moreover, studies have suggested that female sex hormones amplify memory immune responses, which may lead to an excessive immune response impacting the pathogenesis, airway hyperresponsiveness, inflammation of airways, and mucus production of allergic diseases. The evidence suggests that estrogens enhance immune humoral responses, autoimmunity, mast cell reactivity, and delayed IV allergic reactions, while androgens, progesterone, and glucocorticoids suppress them. This review explores the relationship between sex hormones and allergies, including epidemiological data, experimental findings, and insights from animal models. We discuss the general properties of these hormones, their effects on allergic processes, and clinical observations and therapeutic results. Finally, we describe hypersensitivity reactions to these hormones.

Merkel cell carcinoma (MCC) and melanoma are important contributors to skin cancer mortality in the United States. We evaluated their epidemiology using the United States cancer registry data. In 2000-2021, 19,444 MCCs and 646,619 melanomas of the skin were diagnosed. Ninety percent of MCCs and 95% of melanomas were in non-Hispanic White individuals. More than 70% of MCCs versus 37% of melanomas occurred in people aged ≥70 years. Excess MCCs and melanomas were observed on the head and neck (observed:expected: MCC, 5.15; melanoma, 2.47). Among non-Hispanic White individuals, ambient UVR exposure was associated with melanoma arising on the head and neck (incidence rate ratios of 1.15-1.20 for MCC and 1.24-1.49 for melanoma, comparing quintiles 3-5 with quintile 1). Cancer-specific mortality was higher among patients with MCC than among those with melanoma (hazard ratio = 2.33, 95% confidence interval = 2.26-2.42) but improved in both groups after 2011 when BRAF and checkpoint inhibitors were introduced. In conclusion, melanoma exhibited stronger associations with race and ambient UVR exposure, while MCC was more likely to arise on the head and neck (perhaps reflecting the distribution of precursor cells). To ensure prompt treatment, clinicians should be on alert when diagnosing these cancers.

Non-tuberculous mycobacteria (NTM) are one of major public health concern. The current study aimed to find the prevalence trends of NTM in Guangzhou, China from January 2018 to December 2023. A total of 26,716 positive mycobacterial cultures were collected. Thirty-six specimens with incomplete personal information were excluded. The remaining 26,680 specimens were identified using a gene chip method. 16,709 isolates were Mycobacterium tuberculosis (MTB) (62.63 %), and 9,971 were NTM (37.37 %). 43.43 % (4,330/9,971) of NTM isolates were male, and 56.57 % (5,641/9,971) were female (χ2 = 24.36, P < 0.05), a male to female ratio of approximately 1:1.30. Infections in individuals with aged 40 years and above was higher (77.63 %) than below 40 years (22.37 %) (χ2 = 4.94, P = 0.026). The annual NTM isolation rates from 2018 to 2023 were 32.03 %, 34.00 %, 36.27 %, 38.58 %, 38.99 %, and 43.24 %, respectively, showing an increasing trend (χ2 for trend = 0.097, P < 0.05) (R = 0.097, P < 0.05). Out of 9,971 NTM isolates, 8,881 cases include only five common NTM species (MAC, M. abscessus/M. chelonae, M. kansasii, M. fortuitum, and M. gordonae). The overall NTM isolation rate was 37.37 %. The NTM isolation rate was significantly higher than the national average, showing an increasing trend over the last six years.

Rheumatoid arthritis (RA) is a chronic autoimmune inflammatory disease whose etiology is not fully understood. Defective peripheral immune tolerance and subsequent mis‑differentiation and aberrant infiltration of synovium by various immune cells, especially helper T (Th) cells, play an important role in the development of RA. There are significant sex differences in RA, but the results of studies on the effects of sex hormones on RA have been difficult to standardize and hormone replacement therapy has been limited by the potential for serious side effects. Existing research has amply demonstrated that cellular immune responses are largely determined by sex and that sex hormones play a key role in Th cell responses. Based on the aforementioned background and the plasticity of Th cells, it is reasonable to hypothesize that the action of sex hormones on Th cells will hopefully become a therapeutic target for RA. The present review discussed the role of various Th cell subsets in the pathogenesis of RA and also explored the role of sex hormones on the phenotype and function of these aberrantly regulated immune cells in RA as well as other pathologic effects on RA.

Background/Objectives: HBV infections can lead to serious liver complications that can have fatal consequences. In 2022, around 1.1 million individuals died from HBV-related cirrhosis and hepatocellular carcinoma. Vaccines allow us to save more than 2.5 million lives each year; however, up to 10% of vaccinated individuals may not develop sufficient protective antibody levels. The aim of this study was to investigate the epigenetic drift in the response to HBV vaccine in isolated B cells. Methods: Epigenetic drift was measured by counting rare DNA methylation variants. These epivariants were detected in epigenome-wide data collected from isolated B cell samples from 41 responders and 30 non-responders (age range 22-62 years) to vaccination against HBV. Results: We found an accumulation of epivariants in the NR group, with a significant increase in hyper-methylated aberrations. We identified the chromosomes (1, 3, 11, 12, and 14) and genes (e.g., RUSC1_AS1 or TROVE2) particularly enriched in epivariants in NRs. The literature search and pathway analysis indicate that such genes are involved in the correct functioning of the immune system. Moreover, we observed a correlation between epigenetic drift and DNA methylation entropy in the male population of the cohort. Finally, we confirmed the correlation between epivariant loads and age-related epigenetic clocks. Conclusions: Our findings support the idea that an age-related derangement of the epigenetic architecture is involved in unresponsiveness to the HBV vaccine. Furthermore, the overall results highlight the interconnection between various epigenetic dynamics (such as drift, clocks, and entropy), although these interconnections seem not to be involved in the altered immunological activity.

The COVID-19 pandemic has revolutionized vaccine production and compelled a massive global vaccination campaign. This study aimed to estimate the positivity and levels of SARS-CoV-2 IgG antibodies acquired due to vaccination and infection in the academic population of a Portuguese university.

Blood samples were collected and analyzed through the ELISA methodology, and statistical analysis was performed.

A total of 529 volunteers with at least one dose of the vaccine were enrolled in this study. Individuals without a prior COVID-19 diagnosis were divided into two groups: 350, who received a full vaccination, and 114, who received a full vaccination and a booster dose of the same vaccine (81) and mixed vaccines (33). Regarding the individuals who reported a prior SARS-CoV-2 infection, 31 received a full vaccination, and 34 received only one vaccination dose. Data analysis showed a higher level of IgG against SARS-CoV-2 in individuals who were younger, female, who received the Moderna vaccine, with recent post-vaccine administration, a mixed booster dose, and prior SARS-CoV-2 infection.

Assessing vaccination's effectiveness and group immunity is crucial for pandemic management, particularly in academic environments with high individual mobility, in order to define groups at risk and redirect infection control strategies.

Systemic lupus erythematosus (SLE) is an autoimmune disorder with a complex clinical course and diverse presentations. The immunopathogenesis of SLE has long intrigued physicians and researchers. Despite its extensive global prevalence, there is no specific treatment to prevent and treat SLE, and in the majority of SLE patients, the management involves controlling disease remissions and symptom reactivations or flares. SLE patients suffer from damage to different organs of the body, complicating disease management. They are predisposed to infectious diseases that could contribute to enhanced disease progression. Devising effective management strategies requires a comprehensive understanding of the effects of the disease and its influence on the immune system. SLE affects females more frequently than men. However, male SLE patients often suffer from more severe disease than females. Gender variations have also been noted in clinical manifestations in patients with SLE. In light of this, additional research is needed to understand these variations and promote the progress of gender-specific patient management and treatment strategies. This review aimed to compare the influence of gender on the clinical consequences, immunopathogenesis, and associated consequences between male and female SLE patients. An extensive literature search was conducted to collect relevant data. PubMed, MEDLINE, Embase, and Google Scholar were searched from inception to the present for articles that compared clinical outcomes and associated disorders in terms of gender among SLE patients. We also explored the immunopathogenesis, mechanisms underlying gender-based clinical effects of SLE, and infectious disease-related consequences. Additionally, we provide key updates regarding the treatment and management of SLE.

The COVID-19 pandemic is a major public health challenge. The US Centers for Disease Control published guidelines early in the pandemic emphasizing practicing good hygiene and staying at home, which were later modified.

Using a community sample of 2152 participants in the state of Florida who responded to a series of online surveys, we tested a prediction model of adherence to guidelines and intent to vaccinate during the COVID-19 pandemic.

Participants were assessed in May 2020, June 2020, and January 2021. Predictors included sociodemographic and psychological variables.

A slight decrease in adherence was reported over time. In multivariate models, older age, female sex, having health insurance, greater knowledge about COVID-19, more worry, less loneliness, and greater confidence and trust in COVID-19 information were all significantly and consistently associated with greater adherence to guidelines. Significant predictors of intent to vaccinate were male sex, greater knowledge, higher socioeconomic status, identifying as White, and greater guideline adherence (p's < 0.05).

Our findings highlight a number of significant predictors, including knowledge, loneliness, and confidence/trust. Critically these variables are modifiable and could therefore serve as targets in public health interventions to improve adherence to pandemic guidelines in the general population, as well as certain demographic characteristics that may influence intent to vaccinate. COVID-19 knowledge appears to play a central role in both adherence to guidelines and intent to vaccinate suggesting that having accurate information is critical for appropriate behavior.

Infections during pregnancy are known to trigger alterations in offspring immunity, often leading to increased disease susceptibility. Maternal helminth infections correlate with lower Ab titers to certain childhood immunizations and putative decreased vaccine efficacy. The mechanisms that underlie how maternal infection blunts offspring humoral responses are unclear. Using our murine model of maternal schistosomiasis, we found that maternal helminth infection decreases the germinal center response of all offspring to tetanus immunization. However, only male offspring have defects in memory B cell and long-lived plasma cell generation. We found this sex-specific aberration begins during B cell development within the bone marrow via alteration of the IL-7 niche and persists throughout antigenic activation in the germinal center in the periphery. Critically, these defects in males are cell intrinsic, persisting following adoptive transfer to control male pups. Together, these data show that maternal infections can alter both the bone marrow microenvironment and the development of B lymphocytes in a sex-specific manner. This study correlates maternal infection induced defects in early life B cell development with ineffective Ab responses after vaccination.

The origins of sex differences in human disease are elusive, in part because of difficulties in separating the effects of sex hormones and sex chromosomes. To separate these variables, we examined gene expression in four groups of trans- or cisgender individuals: XX individuals treated with exogenous testosterone (n=21), XY treated with exogenous estradiol (n=13), untreated XX (n=20), and untreated XY (n=15). We performed single-cell RNA-sequencing of 358,426 peripheral blood mononuclear cells. Across the autosomes, 8 genes responded with a significant change in expression to testosterone, 34 to estradiol, and 32 to sex chromosome complement with no overlap between the groups. No sex-chromosomal genes responded significantly to testosterone or estradiol, but X-linked genes responded to sex chromosome complement in a remarkably stable manner across cell types. Through leveraging a four-state study design, we successfully separated the independent actions of testosterone, estradiol, and sex chromosome complement on genome-wide gene expression in humans.

To comprehensively identify and provide an overview of in vivo or clinical studies of nucleic acids (NA)-based vaccines against TB we included human or animal studies of NA vaccines for the prevention or treatment of TB and excluded in vitro or in silico research, studies of microorganisms other than M. tuberculosis, reviews, letters, and low-yield reports.

We searched PubMed, Scopus, Embase, selected Web of Science and ProQuest databases, Google Scholar, eLIBRARY.RU, PROSPERO, OSF Registries, Cochrane CENTRAL, EU Clinical Trials Register, clinicaltrials.gov, and others through WHO International Clinical Trials Registry Platform Search Portal, AVMA and CABI databases, bioRxiv, medRxiv, and others through OSF Preprint Archive Search. We searched the same sources and Google for vaccine names (GX-70) and scanned reviews for references. Data on antigenic composition, delivery systems, adjuvants, and vaccine efficacy were charted and summarized descriptively.

A total of 18,157 records were identified, of which 968 were assessed for eligibility. No clinical studies were identified. 365 reports of 345 animal studies were included in the review. 342 (99.1%) studies involved DNA vaccines, and the remaining three focused on mRNA vaccines. 285 (82.6%) studies used single-antigen vaccines, while 48 (13.9%) used multiple antigens or combinations with adjuvants. Only 12 (3.5%) studies involved multiepitope vaccines. The most frequently used antigens were immunodominant secretory antigens (Ag85A, Ag85B, ESAT6), heat shock proteins, and cell wall proteins. Most studies delivered naked plasmid DNA intramuscularly without additional adjuvants. Only 4 of 17 studies comparing NA vaccines to BCG after M. tuberculosis challenge demonstrated superior protection in terms of bacterial load reduction. Some vaccine variants showed better efficacy compared to BCG.

https://osf.io/, identifier F7P9G.

Although sex hormones are recognized to induce immune variations, the effect of hormonal therapy use on immunity is only poorly understood. Here, we quantified how hormonal therapy use affects HIV-1 immune markers in cis women (CW) and trans women and non-binary people (TNBP) with HIV.

We considered CD4, CD8 and lymphocyte measurements from cis men (CM), CW and TNBP in the Swiss HIV Cohort Study. We modelled HIV-1 markers using linear mixed-effects models with an interaction between 'gender' (CW, TNBP) and 'hormonal therapy use' (yes/no). Models were adjusted on age, ethnicity, education level, time since start of antiretroviral therapy and use of intravenous drugs. We assessed the inflammatory effect of hormonal therapy use in 31 TNBP using serum proteomics measurements of 92 inflammation markers.

We included 54 083 measurements from 3092 CW and 83 TNBP, and 147 230 measurements from 8611 CM. Hormonal therapy use increased CD4 count and CD4:CD8 ratio in TNBP more than in CW (pinteraction = 0.02 and 0.007, respectively). TNBP with hormonal therapy use had significantly higher CD4 counts [median = 772 cells/μL, interquartile range (IQR): 520-1006] than without (617 cells/μL, 426-892). This was similar to the effect of CW versus CM on CD4 T cells. Hormonal therapy use did not affect serum protein concentrations in TNBP.

This study highlights the potential role of hormonal therapy use in modulating the immune system among other biological and social factors, especially in TNBP with HIV.

Anti-drug antibodies (ADA) reduce the efficacy of immunotherapies in multiple sclerosis (MS) and are associated with increased disease progression risk. Blood biomarkers predicting immunogenicity to biopharmaceuticals represent an unmet clinical need. Patients with relapsing remitting (RR)MS were recruited before (baseline), three, and 12 (M12) months after commencing interferon-beta treatment. Neutralising ADA-status was determined at M12, and patients were stratified at baseline according to their M12 ADA-status (ADA-positive/ADA-negative). Patients stratified as ADA-positive were characterised by an early dampened response to interferon-beta (prior to serum ADA detection) and distinct proinflammatory transcriptomic/proteomic peripheral blood signatures enriched for 'immune response activation' including phosphoinositide 3-kinase-γ and NFκB-signalling pathways both at baseline and throughout the treatment course, compared to ADA-negative patients. These immunogenicity-associated proinflammatory signatures significantly overlapped with signatures of MS disease severity. Thus, whole blood molecular profiling is a promising tool for prediction of ADA-development in RRMS and could provide insight into mechanisms of immunogenicity.

Sex differences in immune-based disorders are well-established, with female sex associated with a markedly heightened risk of autoimmune disease. Female sex is also overrepresented in other conditions associated with elevated inflammation, including depression, chronic pain, and chronic fatigue. The mechanisms underlying these disparities are unclear. This study used an experimental model of inflammatory challenge to interrogate molecular mechanisms that may contribute to female vulnerability to disorders with an inflammatory basis.

In this analysis of a secondary outcome from a randomized controlled trial, 111 participants (67 female) received either a bolus injection of endotoxin (n = 59) or placebo (n = 52). Participants provided blood samples before and 0.5 h post-injection for assessment of differential activation of key pro-inflammatory (i.e., activator protein (AP)-1; nuclear factor (NF)-κB) and immunoregulatory (i.e., glucocorticoid receptor (GR); cAMP response element binding protein (CREB)) signaling pathways via genome-wide expression profiling and promoter-based bioinformatics analyses.

Relative to males, females exhibited greater endotoxin-induced increases in bioinformatic measures of CREB transcription factor activity (p's < 0.01). However, contrary to hypotheses, female vs. male sex was not associated with greater increases in activation of NF-κB, AP-1, or GR in response to endotoxin vs. placebo administration.

This work suggests CREB signaling as a critical upstream biological pathway that should be further interrogated as a mechanism of female vulnerability to immune-related disorders. Future work should clarify whether increased CREB signaling indicates sex differences in activity of the sympathetic nervous system or other physiological pathways that signal through CREB, such as prostaglandin release.

COVID-19 outcomes are less severe in women than men suggesting that female sex is protective. The steroids estradiol (E2) and progesterone (P4) promote anti-inflammatory immune responses and their therapeutic use for COVID-19 has been under investigation. The aim of the study was to evaluate the efficacy of a short systemic E2 and P4 combination in mitigating COVID-19 severity in hospitalized men and women. In a phase 2, single center, double blind, randomized placebo-controlled trial, ten male and female participants hospitalized for COVID-19 with scores 3-5 on the 9-point WHO ordinal scale were randomized to receive either (1) E2 cypionate (5 mg, IM) and micronized P4 (200 mg, PO), or (2) placebo-equivalent, in addition to standard of care (SOC). The primary outcome was the proportion of patients whose WHO scores improved to 1-2 on the day of discharge. Secondary outcomes included length of hospital stay (LOS), days on oxygen therapy (DOT), readmission rates (RR), adverse events (AEs), and change in circulating biomarkers using untargeted proteomics and cytokine profiling. There were no significant changes between the groups in primary outcome, LOS, DOT, RR or AEs. The E2P4 group exhibited a decrease in biomarker pathways of respiratory and gastrointestinal disease inflammation, infection by coronavirus, and immune cell trafficking and inflammatory response. A short-term E2P4 treatment in patients hospitalized for COVID-19 decreases biomarkers of inflammation. Considering the availability, low cost, and safety of E2 and P4, our results warrant additional studies to explore their effects in mitigating other viral pandemics. Clinical Trial Registration NCT04865029, ClinicalTrials.gov; (First trial registration 29/04/2021).

Sex differences exist not only in the efficacy but also in adverse event rates of many vaccines. Here we compared the safety of BNT162b2 vaccine administered off-label in female and male children younger than 5 years in Germany.

This is a retrospective cohort study, in which we performed a post-hoc analysis of a dataset collected through an authentication-based survey of individuals having registered children aged 0-<5 years for vaccination against SARS-CoV-2 in six private practices and/or two lay person-initiated vaccination campaigns. We analyzed the safety profiles of the first 3 doses of 3-10 µg BNT162b2. Primary outcome was comparison in frequencies of 4 common post-vaccination symptom categories such as local, general, musculoskeletal symptoms and fever. Data were analyzed according to sex in bivariate analyses and regression models adjusting for age, weight, and dosage. Interaction between sex and BNT162b2 dosage was assessed. An active-comparator analysis was applied to compare post-vaccination symptoms after BNT162b2 versus non-SARS-CoV-2 vaccines.

The dataset for the present analysis consisted of 7801 participants including 3842 females (49%) and 3977 males (51%) with an age of 3 years (median, interquartile: 2 years). Among individuals receiving 3 µg BNT162b2, no sex differences were noted, but after a first dose of 5-10 µg BNT162b2, local injection-site symptoms were more prevalent in girls compared to boys. In logistic regression, female sex was associated with higher odds of local symptoms, odds ratio (OR) of 1.33 (95% confidence interval [CI]: 1.15-1.55, p < 0.05) and general symptoms with OR 1.21 (95% CI: 1.01-1.44, p < 0.05). Following non-BNT162b2 childhood vaccinations, female sex was associated with a lower odds of post-vaccination musculoskeletal symptoms (OR: 0.29, 95% CI: 0.11-0.82, p < 0.05). An active comparator analysis between BNT162b2 and non-SARS-CoV-2 vaccinations revealed that female sex positively influenced the association between BNT162b2 vaccine type and musculoskeletal symptoms.

Sex differences exist in post-vaccination symptoms after BNT162b2 administration even in young children. These are of importance for the conception of approval studies, for post-vaccination monitoring and for future vaccination strategies (German Clinical Trials Register ID: DRKS00028759).

Development of an effective vaccine against tuberculosis is a critical step towards reducing the global burden of disease. A therapeutic vaccine might also reduce the high rate of TB recurrence and help address the challenges of drug-resistant strains. ID93+GLA-SE is a candidate subunit vaccine that will soon be evaluated in a phase 2b efficacy trial for prevention of recurrent TB among patients undergoing TB treatment. ID93+GLA-SE vaccination was shown to elicit robust CD4+ T cell and IgG antibody responses among recently treated TB patients in the TBVPX-203 Phase 2a study (NCT02465216), but the mechanisms underlying these responses are not well understood.

In this study we used specimens from TBVPX-203 participants to describe the changes in peripheral blood gene expression that occur after ID93+GLA-SE vaccination.

Analyses revealed several distinct modules of co-varying genes that were either up- or down-regulated after vaccination, including genes associated with innate immune pathways at 3 days post-vaccination and genes associated with lymphocyte expansion and B cell activation at 7 days post-vaccination. Notably, the regulation of these gene modules was affected by the dose schedule and by participant sex, and early innate gene signatures were correlated with the ID93-specific CD4+ T cell response.

The results provide insight into the complex interplay of the innate and adaptive arms of the immune system in developing responses to vaccination with ID93+GLA-SE and demonstrate how dosing and schedule can affect vaccine responses.