ArticleProceedings of the National Academy of Sciences of the United States of America2014
Systems analysis of sex differences reveals an immunosuppressive role for testosterone in the response to influenza vaccination.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to 2 registered trials, which are not on this map. Cited by 423 papers, 2 of them syntheses that pooled it.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Immune Senescence in the Elderly: Comparison of Immune Responses to Influenza Vaccine In Adults of Different Ages
Clifford Craig Vaccine Trial Centre: Heterologous Effect of Diptheria, Tetanus, Acellular Pertussis Vaccination on Influenza Vaccine Challenge in the Elderly
Who cites it
423 citing papers in PubMed, 2 syntheses or guidelines pooled it, 680 citations in OpenAlex.
- A preclinical systematic review and meta-analysis assessing the effect of biological sex in lipopolysaccharide-induced acute lung injury.American journal of physiology. Lung cellular and molecular physiology · 2024Pooled it
- COVID-19 pandemic: insights into molecular mechanisms leading to sex-based differences in patient outcomes.Expert reviews in molecular medicine · 2021Pooled it
- A Phase 1 Randomized, Placebo-Controlled Study Evaluating the Safety, Tolerability, and Pharmacokinetics of Enteric-Coated Stabilized Sulforaphane (SFX-01) in Male Participants.Advances in therapy · 2025Trial
- Multimodal single-cell omics analysis identifies epithelium-immune cell interactions and immune vulnerability associated with sex differences in COVID-19.Signal transduction and targeted therapy · 2021Trial
- The Association Between ABO Blood Groups and Neonatal Clinical Outcomes Among Infants Admitted to the Neonatal Intensive Care Unit of Imam Khomeini Hospital in Ahvaz, Iran, During 2023-2024: A Retrospective Descriptive Study.Health science reports · 2026Article
- Sex-Biased Immunity: The Hidden Variable in Immuno-oncology.Clinical cancer research : an official journal of the American Association for Cancer Research · 2026Review
- Sex-specific aging clocks from a large-scale human phenome reveal distinct aging transitions and circulating signatures.Nature aging · 2026Article
- Effect of Latanoprost and Timolol-Dorzolamide Therapy on Aqueous Humor Cytokine Concentrations in Patients with Pseudoexfoliative Glaucoma.Medicina (Kaunas, Lithuania) · 2026Observational
- Sex-specific trajectories of nonlinear immune aging at single-cell level.Nature communications · 2026Article
- Review
- Pre-existing hemagglutinin-specific antibody levels are associated with B-cell repertoire maturation and antibody breadth after influenza vaccination.Virologica Sinica · 2026Article
- Five-year immunogenicity and safety follow-up of the PREVAC randomized Trial of Vaccines for Zaire Ebola Virus Disease.medRxiv : the preprint server for health sciences · 2026Article
- Association between sex hormones and innate cytotoxic capacity of circulating and rectal mucosal immune cells.Clinical immunology communications · 2026Article
- Sex differences in the long-term tolerability of BNT162b2 in children and adolescents.Molecular and cellular pediatrics · 2026Article
- Female reproductive status and ecological conditions impact the magnitude of sex differences in human immune status across the lifespan.Research square · 2026Article
- Risk of complications after total hip arthroplasty in patients on testosterone replacement therapy.European journal of orthopaedic surgery & traumatology : orthopedie traumatologie · 2026Article
- The systemic immune-inflammation index combined with the platelet-to-lymphocyte ratio demonstrates notable potential as a prognostic tool for older adults with pneumonia caused by influenza A virus infection: a retrospective cohort study.BMC pulmonary medicine · 2026Article
- The problem with one-size-fits-all medicine: Biological sex and the aging immune system.PLoS biology · 2026Article
- Sexual dimorphism of COVID-19 inspires drug repositioning and host-targeting immunotherapy for viral pneumonia.Signal transduction and targeted therapy · 2026Article
- Poor sleep impairs immune responses and influenza vaccine protection.Nature communications · 2026Article
363 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
8 authors at 4 institutions in 2 countries.
Funding
Abstract
Females have generally more robust immune responses than males for reasons that are not well-understood. Here we used a systems analysis to investigate these differences by analyzing the neutralizing antibody response to a trivalent inactivated seasonal influenza vaccine (TIV) and a large number of immune system components, including serum cytokines and chemokines, blood cell subset frequencies, genome-wide gene expression, and cellular responses to diverse in vitro stimuli, in 53 females and 34 males of different ages. We found elevated antibody responses to TIV and expression of inflammatory cytokines in the serum of females compared with males regardless of age. This inflammatory profile correlated with the levels of phosphorylated STAT3 proteins in monocytes but not with the serological response to the vaccine. In contrast, using a machine learning approach, we identified a cluster of genes involved in lipid biosynthesis and previously shown to be up-regulated by testosterone that correlated with poor virus-neutralizing activity in men. Moreover, men with elevated serum testosterone levels and associated gene signatures exhibited the lowest antibody responses to TIV. These results demonstrate a strong association between androgens and genes involved in lipid metabolism, suggesting that these could be important drivers of the differences in immune responses between males and females.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.