Fish, E. N. The X-files in immunity: sex-based differences predispose immune responses. Nat. Rev. Immunol. 8, 737–744 (2008). This review compiles a comprehensive table of immune-related genes on the X chromosome and synthesizes evidence from the literature showing that some of these genes escape XCI, resulting in increaed gene dosage.

Article 
CAS 
PubMed 
PubMed Central 

Google Scholar
 

Cheng, M. I. et al. The X-linked epigenetic regulator UTX controls NK cell-intrinsic sex differences. Nat. Immunol. 24, 780–791 (2023).

Article 
CAS 
PubMed 
PubMed Central 

Google Scholar
 

Cunningham, M. A., Wirth, J. R., Naga, O., Eudaly, J. & Gilkeson, G. S. Estrogen receptor α binding to ERE is required for full Tlr7- and Tlr9-induced inflammation. SOJ Immunol 2, 7 (2014).

Article 

Google Scholar
 

Klein, S. L. & Flanagan, K. L. Sex differences in immune responses. Nat. Rev. Immunol. 16, 626–638 (2016). This seminal paper is often credited with defining the field of sex differences in immunity. The review examines immune responses across a range of diseases and presents evidence for the the evolutionary emergence of sex-based differences in immunity across species.

Article 
CAS 
PubMed 

Google Scholar
 

Dunn, S. E., Perry, W. A. & Klein, S. L. Mechanisms and consequences of sex differences in immune responses. Nat. Rev. Nephrol. 20, 37–55 (2024).

Article 
CAS 
PubMed 

Google Scholar
 

Libert, C., Dejager, L. & Pinheiro, I. The X chromosome in immune functions: when a chromosome makes the difference. Nat. Rev. Immunol. 10, 594–604 (2010).

Article 
CAS 
PubMed 

Google Scholar
 

Case, L. K. et al. Chromosome y regulates survival following murine coxsackievirus b3 infection. G3 2, 115–121 (2012).

Article 
CAS 
PubMed 
PubMed Central 

Google Scholar
 

Arnold, A. P. X chromosome agents of sexual differentiation. Nat. Rev. Endocrinol. 18, 574–583 (2022).

Article 
CAS 
PubMed 
PubMed Central 

Google Scholar
 

Berletch, J. B. et al. Escape from X inactivation varies in mouse tissues. PLoS Genet. 11, e1005079 (2015).

Article 
PubMed 
PubMed Central 

Google Scholar
 

Carrel, L. & Willard, H. F. X-inactivation profile reveals extensive variability in X-linked gene expression in females. Nature 434, 400–404 (2005).

Article 
CAS 
PubMed 

Google Scholar
 

Arnold, A. P. Four core genotypes and XY* mouse models: Update on impact on SABV research. Neurosci. Biobehav. Rev. 119, 1–8 (2020).

Article 
CAS 
PubMed 
PubMed Central 

Google Scholar
 

Itoh, Y. et al. The X-linked histone demethylase Kdm6a in CD4+ T lymphocytes modulates autoimmunity. J. Clin. Invest. 129, 3852–3863 (2019). This paper clearly demonstrates how X-chromosome gene dosage influences immune cell function and shapes disease outcomes.

Article 
PubMed 
PubMed Central 

Google Scholar
 

Hagen, S. H. et al. Heterogeneous escape from X chromosome inactivation results in sex differences in type I IFN responses at the single human pDC level. Cell Rep. 33, 108485 (2020).

Article 
CAS 
PubMed 
PubMed Central 

Google Scholar
 

Rubtsov, A. V. et al. Toll-like receptor 7 (TLR7)-driven accumulation of a novel CD11c+ B-cell population is important for the development of autoimmunity. Blood 118, 1305–1315 (2011).

Article 
CAS 
PubMed 
PubMed Central 

Google Scholar
 

Blanton, L. V. et al. Stable and robust Xi and Y transcriptomes drive cell-type-specific autosomal and Xa responses in vivo and in vitro in four human cell types. Cell Genom. 4, 100628 (2024).

Article 
CAS 
PubMed 
PubMed Central 

Google Scholar
 

Dutta, S. & Sengupta, P. Men and mice: relating their ages. Life Sci. 152, 244–248 (2016).

Article 
CAS 
PubMed 

Google Scholar
 

Potluri, T. et al. Age-associated changes in the impact of sex steroids on influenza vaccine responses in males and females. NPJ Vaccines 4, 29 (2019).

Article 
PubMed 
PubMed Central 

Google Scholar
 

Fox, H. S., Bond, B. L. & Parslow, T. G. Estrogen regulates the IFN-γ promoter. J. Immunol. 146, 4362–4367 (1991).

Article 
CAS 
PubMed 

Google Scholar
 

Heldring, N. et al. Estrogen receptors: how do they signal and what are their targets. Physiol. Rev. 87, 905–931 (2007).

Article 
CAS 
PubMed 

Google Scholar
 

Kovats, S. Estrogen receptors regulate innate immune cells and signaling pathways. Cell. Immunol. 294, 63–69 (2015).

Article 
CAS 
PubMed 
PubMed Central 

Google Scholar
 

Hoffmann, J. P., Liu, J. A., Seddu, K. & Klein, S. L. Sex hormone signaling and regulation of immune function. Immunity 56, 2472–2491 (2023).

Article 
CAS 
PubMed 

Google Scholar
 

Thiebaut, C., Vlaeminck-Guillem, V., Trédan, O., Poulard, C. & Le Romancer, M. Non-genomic signaling of steroid receptors in cancer. Mol. Cell. Endocrinol. 538, 111453 (2021).

Article 
CAS 
PubMed 

Google Scholar
 

Lei, K. et al. Progesterone acts via the nuclear glucocorticoid receptor to suppress IL-1β-induced COX-2 expression in human term myometrial cells. PLoS ONE 7, e50167 (2012).

Article 
CAS 
PubMed 
PubMed Central 

Google Scholar
 

Merlino, A. A. et al. Nuclear progesterone receptors in the human pregnancy myometrium: evidence that parturition involves functional progesterone withdrawal mediated by increased expression of progesterone receptor-A. J. Clin. Endocrinol. Metab. 92, 1927–1933 (2007).

Article 
CAS 
PubMed 

Google Scholar
 

Su, L. et al. Progesterone inhibits Toll-like receptor 4-mediated innate immune response in macrophages by suppressing NF-κB activation and enhancing SOCS1 expression. Immunol. Lett. 125, 151–155 (2009).

Creisher, P. S. & Klein, S. L. Pathogenesis of viral infections during pregnancy. Clin. Microbiol. Rev. 37, e0007323 (2024).

Article 
PubMed 
PubMed Central 

Google Scholar
 

Berghofer, B. et al. TLR7 ligands induce higher IFN-α production in females. J. Immunol. 177, 2088–2096 (2006).

Article 
PubMed 

Google Scholar
 

Meier, A. et al. Sex differences in the Toll-like receptor-mediated response of plasmacytoid dendritic cells to HIV-1. Nat. Med. 15, 955–959 (2009). This study shows sex-differential innate immune sensing of HIV-1 by pDCs, with cells from female individuals producing more IFNα in response to HIV-1-derived TLR7/TLR8 ligands than cells from male individuals, providing insights into how female individuals have a stronger overall immune response during infection.

Article 
CAS 
PubMed 
PubMed Central 

Google Scholar
 

Ziegler, S. M. et al. Human pDCs display sex-specific differences in type I interferon subtypes and interferon α/β receptor expression. Eur. J. Immunol. 47, 251–256 (2017).

Article 
CAS 
PubMed 

Google Scholar
 

Seillet, C. et al. The TLR-mediated response of plasmacytoid dendritic cells is positively regulated by estradiol in vivo through cell-intrinsic estrogen receptor alpha signaling. Blood 119, 454–464 (2012).

Article 
CAS 
PubMed 

Google Scholar
 

Wang, J. P., Zhang, L., Madera, R. F., Woda, M. & Libraty, D. H. Plasmacytoid dendritic cell interferon-α production to R-848 stimulation is decreased in male infants. BMC Immunol. 13, 35 (2012).

Article 
CAS 
PubMed 
PubMed Central 

Google Scholar
 

Webb, K. et al. Sex and pubertal differences in the type 1 interferon pathway associate with both X chromosome number and serum sex hormone concentration. Front. Immunol. 9, 3167 (2018).

Article 
CAS 
PubMed 

Google Scholar
 

Griesbeck, M. et al. Sex differences in plasmacytoid dendritic cell levels of IRF5 drive higher IFN-α production in women. J. Immunol. 195, 5327–5336 (2015).

Article 
CAS 
PubMed 
PubMed Central 

Google Scholar
 

Laffont, S. et al. X-Chromosome complement and estrogen receptor signaling independently contribute to the enhanced TLR7-mediated IFN-alpha production of plasmacytoid dendritic cells from women. J. Immunol. 193, 5444–5452 (2014).

Article 
CAS 
PubMed 

Google Scholar
 

Souyris, M. et al. TLR7 escapes X chromosome inactivation in immune cells. Sci. Immunol. 3, eaap8855 (2018). This study shows that TLR7 escapes XCI in B cells and myeloid cells from XX female individuals and individuals with Klinefelter syndrome.

Article 
PubMed 

Google Scholar
 

Grunhagel, B. et al. Reduction of IFN-I responses by plasmacytoid dendritic cells in a longitudinal trans men cohort. iScience 26, 108209 (2023).

Article 
PubMed 
PubMed Central 

Google Scholar
 

Lakshmikanth, T. et al. Immune system adaptation during gender-affirming testosterone treatment. Nature 633, 155–164 (2024).

Article 
CAS 
PubMed 
PubMed Central 

Google Scholar
 

Scotland, R. S., Stables, M. J., Madalli, S., Watson, P. & Gilroy, D. W. Sex differences in resident immune cell phenotype underlie more efficient acute inflammatory responses in female mice. Blood 118, 5918–5927 (2011).

Article 
CAS 
PubMed 
PubMed Central 

Google Scholar
 

Jabeen, S. et al. TLR4 sex dimorphism correlates with sex dimorphic phagocytosis in primary macrophages. J. Gend. Specif. Med. 6, 100–106 (2020).


Google Scholar
 

Ter Horst, R. et al. Host and environmental factors influencing individual human cytokine responses. Cell 167, 1111–1124 (2016).

Article 
PubMed 
PubMed Central 

Google Scholar
 

De Maeyer, R. P. H. et al. Age-associated inflammatory monocytes are increased in menopausal females and reversed by hormone replacement therapy. Aging Cell 24, e70249 (2025).

Article 
PubMed 
PubMed Central 

Google Scholar
 

Di Florio, D. N., Sin, J., Coronado, M. J., Atwal, P. S. & Fairweather, D. Sex differences in inflammation, redox biology, mitochondria and autoimmunity. Redox Biol. 31, 101482 (2020).

Article 
PubMed 
PubMed Central 

Google Scholar
 

Alves, T. et al. Inflammasome targeting for periodontitis prevention is sex dependent. Proc. Natl Acad. Sci. USA 122, e2507092122 (2025).

Article 
CAS 
PubMed 
PubMed Central 

Google Scholar
 

Huang, Z. et al. Effects of sex and aging on the immune cell landscape as assessed by single-cell transcriptomic analysis. Proc. Natl Acad. Sci. USA 118, e2023216118 (2021).

Article 
CAS 
PubMed 
PubMed Central 

Google Scholar
 

Zhang, M. A. et al. Antagonizing peroxisome proliferator-activated receptor alpha activity selectively enhances TH1 immunity in male mice. J. Immunol. 195, 5189–5202 (2015).

Article 
CAS 
PubMed 

Google Scholar
 

Blanquart, E., Laffont, S. & Guery, J. C. Sex hormone regulation of innate lymphoid cells. Biomed. J. 44, 144–156 (2021).

Article 
CAS 
PubMed 

Google Scholar
 

Zychlinsky Scharff, A. et al. Sex differences in IL-17 contribute to chronicity in male versus female urinary tract infection. JCI Insight 5, e122998 (2019).

Article 
PubMed 
PubMed Central 

Google Scholar
 

Darboe, A. et al. Age-related dynamics of circulating innate lymphoid cells in an African population. Front. Immunol. 11, 594107 (2020).

Article 
CAS 
PubMed 
PubMed Central 

Google Scholar
 

Kadel, S. et al. A major population of functional KLRG1− ILC2s in female lungs contributes to a sex bias in ILC2 numbers. Immunohorizons 2, 74–86 (2018).

Article 
CAS 
PubMed 
PubMed Central 

Google Scholar
 

Cephus, J. Y. et al. Testosterone attenuates group 2 innate lymphoid cell-mediated airway inflammation. Cell Rep. 21, 2487–2499 (2017).

Article 
CAS 
PubMed 
PubMed Central 

Google Scholar
 

Laffont, S. et al. Androgen signaling negatively controls group 2 innate lymphoid cells. J. Exp. Med. 214, 1581–1592 (2017).

Article 
CAS 
PubMed 
PubMed Central 

Google Scholar
 

Chi, L. et al. Sexual dimorphism in skin immunity is mediated by an androgen-ILC2-dendritic cell axis. Science 384, eadk6200 (2024).

Article 
CAS 
PubMed 
PubMed Central 

Google Scholar
 

Vom Steeg, L. G., Flores-Garcia, Y., Zavala, F. & Klein, S. L. Irradiated sporozoite vaccination induces sex-specific immune responses and protection against malaria in mice. Vaccine 37, 4468–4476 (2019).

Article 
CAS 
PubMed 
PubMed Central 

Google Scholar
 

Peacock, J. W. et al. Gender differences in human immunodeficiency virus type 1-specific CD8 responses in the reproductive tract and colon following nasal peptide priming and modified vaccinia virus Ankara boosting. J. Virol. 78, 13163–13172 (2004).

Article 
CAS 
PubMed 
PubMed Central 

Google Scholar
 

Amadori, A. et al. Genetic control of the CD4/CD8 T-cell ratio in humans. Nat. Med. 1, 1279–1283 (1995).

Article 
CAS 
PubMed 

Google Scholar
 

Breznik, J. A., Schulz, C., Ma, J., Sloboda, D. M. & Bowdish, D. M. E. Biological sex, not reproductive cycle, influences peripheral blood immune cell prevalence in mice. J. Physiol. 599, 2169–2195 (2021).

Article 
CAS 
PubMed 

Google Scholar
 

Gui, J., Mustachio, L. M., Su, D. M. & Craig, R. W. Thymus size and age-related thymic involution: early programming, sexual dimorphism, progenitors and stroma. Aging Dis. 3, 280–290 (2012).

PubMed 
PubMed Central 

Google Scholar
 

Olsen, N. J., Olson, G., Viselli, S. M., Gu, X. & Kovacs, W. J. Androgen receptors in thymic epithelium modulate thymus size and thymocyte development. Endocrinology 142, 1278–1283 (2001).

Article 
CAS 
PubMed 

Google Scholar
 

Cua, D. J., Hinton, D. R. & Stohlman, S. A. Self-antigen-induced Th2 responses in experimental allergic encephalomyelitis (EAE)-resistant mice. Th2-mediated suppression of autoimmune disease. J. Immunol. 155, 4052–4059 (1995).

Article 
CAS 
PubMed 

Google Scholar
 

Dunn, S. E. et al. Peroxisome proliferator-activated receptor (PPAR)α expression in T cells mediates gender differences in development of T cell-mediated autoimmunity. J. Exp. Med. 204, 321–330 (2007).

Article 
CAS 
PubMed 
PubMed Central 

Google Scholar
 

Zhang, M. A. et al. Peroxisome proliferator-activated receptor (PPAR)α and -γ regulate IFNγ and IL-17A production by human T cells in a sex-specific way. Proc. Natl Acad. Sci. USA 109, 9505–9510 (2012).

Article 
CAS 
PubMed 
PubMed Central 

Google Scholar
 

Hewagama, A., Patel, D., Yarlagadda, S., Strickland, F. M. & Richardson, B. C. Stronger inflammatory/cytotoxic T-cell response in women identified by microarray analysis. Genes Immun. 10, 509–516 (2009).

Article 
CAS 
PubMed 
PubMed Central 

Google Scholar
 

Crotty, S. T. Follicular helper cell biology: a decade of discovery and diseases. Immunity 50, 1132–1148 (2019).

Article 
CAS 
PubMed 
PubMed Central 

Google Scholar
 

Park, H. J., Park, H. S., Lee, J. U., Bothwell, A. L. & Choi, J. M. Gender-specific differences in PPARγ regulation of follicular helper T cell responses with estrogen. Sci. Rep. 6, 28495 (2016).

Article 
PubMed 
PubMed Central 

Google Scholar
 

Kim, S. J., Zou, Y. R., Goldstein, J., Reizis, B. & Diamond, B. Tolerogenic function of Blimp-1 in dendritic cells. J. Exp. Med. 208, 2193–2199 (2011).

Article 
CAS 
PubMed 
PubMed Central 

Google Scholar
 

Vignali, D. A., Collison, L. W. & Workman, C. J. How regulatory T cells work. Nat. Rev. Immunol. 8, 523–532 (2008).

Article 
CAS 
PubMed 
PubMed Central 

Google Scholar
 

Robinson, G. A. et al. Investigating sex differences in T regulatory cells from cisgender and transgender healthy individuals and patients with autoimmune inflammatory disease: a cross-sectional study. Lancet Rheumatol. 4, e710–e724 (2022).

Article 
CAS 
PubMed 
PubMed Central 

Google Scholar
 

Afshan, G., Afzal, N. & Qureshi, S. CD4+CD25hi regulatory T cells in healthy males and females mediate gender difference in the prevalence of autoimmune diseases. Clin. Lab. 58, 567–571 (2012).

PubMed 

Google Scholar
 

Kondo, H. et al. Markers of memory CD8 T cells depicting the effect of the BNT162b2 mRNA COVID-19 vaccine in Japan. Front. Immunol. 13, 836923 (2022).

Article 
CAS 
PubMed 
PubMed Central 

Google Scholar
 

Yee Mon, K. J. et al. Differential sensitivity to IL-12 drives sex-specific differences in the CD8+ T cell response to infection. Immunohorizons 3, 121–132 (2019).

Article 
PubMed 
PubMed Central 

Google Scholar
 

Rukavina, D. et al. Age-related decline of perforin expression in human cytotoxic T lymphocytes and natural killer cells. Blood 92, 2410–2420 (1998).

Article 
CAS 
PubMed 

Google Scholar
 

Guan, X. et al. Androgen receptor activity in T cells limits checkpoint blockade efficacy. Nature 606, 791–796 (2022).

Article 
CAS 
PubMed 
PubMed Central 

Google Scholar
 

Yang, C. et al. Androgen receptor-mediated CD8+ T cell stemness programs drive sex differences in antitumor immunity. Immunity 55, 1268–1283 (2022).

Article 
CAS 
PubMed 

Google Scholar
 

Kwon, H. et al. Androgen conspires with the CD8+ T cell exhaustion program and contributes to sex bias in cancer. Sci. Immunol. 7, eabq2630 (2022).

Article 
CAS 
PubMed 
PubMed Central 

Google Scholar
 

Surman, S. L. et al. How estrogen, testosterone, and sex differences influence serum immunoglobulin isotype patterns in mice and humans. Viruses 15, 482 (2023).

Article 
CAS 
PubMed 
PubMed Central 

Google Scholar
 

Peckham, H. et al. Estrogen influences class-switched memory B cell frequency only in humans with two X chromosomes. J. Exp. Med. 222, e20241253 (2025).

Article 
CAS 
PubMed 
PubMed Central 

Google Scholar
 

Fink, A. L. & Klein, S. L. The evolution of greater humoral immunity in females than males: implications for vaccine efficacy. Curr. Opin. Physiol. 6, 16–20 (2018).

Article 
PubMed 
PubMed Central 

Google Scholar
 

Flanagan, K. L., Fink, A. L., Plebanski, M. & Klein, S. L. Sex and gender differences in the outcomes of vaccination over the life course. Annu. Rev. Cell Dev. Biol. 33, 577–599 (2017).

Article 
CAS 
PubMed 

Google Scholar
 

Mohanram, V. et al. B cell responses associated with vaccine-induced delayed SIVmac251 acquisition in female rhesus macaques. J. Immunol. 197, 2316–2324 (2016).

Article 
CAS 
PubMed 
PubMed Central 

Google Scholar
 

Tuero, I. et al. Mucosal B cells are associated with delayed SIV acquisition in vaccinated female but not male rhesus macaques following SIVmac251 rectal challenge. PLoS Pathog. 11, e1005101 (2015).

Article 
PubMed 
PubMed Central 

Google Scholar
 

Fink, A. L., Engle, K., Ursin, R. L., Tang, W. Y. & Klein, S. L. Biological sex affects vaccine efficacy and protection against influenza in mice. Proc. Natl Acad. Sci. USA 115, 12477–12482 (2018).

Article 
CAS 
PubMed 
PubMed Central 

Google Scholar
 

Farzadegan, H. et al. Sex differences in HIV-1 viral load and progression to AIDS. Lancet 352, 1510–1514 (1998). This study is among the first to provide large-scale clinical evidence that female individuals have lower HIV-1 viral loads than male individuals at comparable stages of infection, yet experience faster progression to AIDS.

Article 
CAS 
PubMed 

Google Scholar
 

Scully, E. P. et al. Sex-based differences in human immunodeficiency virus type 1 reservoir activity and residual immune activation. J. Infect. Dis. 219, 1084–1094 (2019).

Article 
CAS 
PubMed 
PubMed Central 

Google Scholar
 

Das, B. et al. Estrogen receptor-1 is a key regulator of HIV-1 latency that imparts gender-specific restrictions on the latent reservoir. Proc. Natl Acad. Sci. USA 115, E7795–E7804 (2018).

Article 
CAS 
PubMed 
PubMed Central 

Google Scholar
 

Rubin, L. H. et al. Sex differences in neurocognitive function in adults with HIV: patterns, predictors, and mechanisms. Curr. Psychiatry Rep. 21, 94 (2019).

Article 
PubMed 
PubMed Central 

Google Scholar
 

Szotek, E. L., Narasipura, S. D. & Al-Harthi, L. 17β-estradiol inhibits HIV-1 by inducing a complex formation between β-catenin and estrogen receptor α on the HIV promoter to suppress HIV transcription. Virology 443, 375–383 (2013).

Article 
CAS 
PubMed 
PubMed Central 

Google Scholar
 

Chang, J. J. et al. Higher expression of several interferon-stimulated genes in HIV-1-infected females after adjusting for the level of viral replication. J. Infect. Dis. 208, 830–838 (2013).

Article 
CAS 
PubMed 
PubMed Central 

Google Scholar
 

Ziegler, S. & Altfeld, M. Sex differences in HIV-1-mediated immunopathology. Curr. Opin. HIV AIDS 11, 209–215 (2016).

Article 
CAS 
PubMed 
PubMed Central 

Google Scholar
 

Prodger, J. L. et al. Reduced HIV-1 latent reservoir outgrowth and distinct immune correlates among women in Rakai, Uganda. JCI Insight 5, e139287 (2020).

Article 
PubMed 
PubMed Central 

Google Scholar
 

Yu, M. W. et al. Androgen-receptor gene CAG repeats, plasma testosterone levels, and risk of hepatitis B-related hepatocellular carcinoma. J. Natl Cancer Inst. 92, 2023–2028 (2000).

Article 
CAS 
PubMed 

Google Scholar
 

Brown, R., Goulder, P. & Matthews, P. C. Sexual Dimorphism in chronic hepatitis B virus (HBV) infection: evidence to inform elimination efforts. Wellcome Open Res. 7, 32 (2022).

Article 
PubMed 
PubMed Central 

Google Scholar
 

Ruggieri, A., Gagliardi, M. C. & Anticoli, S. Sex-Dependent outcome of hepatitis B and C viruses infections: synergy of sex hormones and immune responses? Front. Immunol. 9, 2302 (2018).

Article 
PubMed 
PubMed Central 

Google Scholar
 

Chan, W. K., Klock, G. & Bernard, H. U. Progesterone and glucocorticoid response elements occur in the long control regions of several human papillomaviruses involved in anogenital neoplasia. J. Virol. 63, 3261–3269 (1989).

Article 
CAS 
PubMed 
PubMed Central 

Google Scholar
 

Grebely, J. et al. The effects of female sex, viral genotype, and IL28B genotype on spontaneous clearance of acute hepatitis C virus infection. Hepatology 59, 109–120 (2014).

Article 
CAS 
PubMed 

Google Scholar
 

Breidbart, S., Burk, R. D. & Saenger, P. Hormonal regulation of hepatitis B virus gene expression: influence of androgen receptor. Pediat. Res. 34, 300–302 (1993).

Article 
CAS 
PubMed 

Google Scholar
 

Farza, H. et al. Hepatitis B surface antigen gene expression is regulated by sex steroids and glucocorticoids in transgenic mice. Proc. Natl Acad. Sci. USA 84, 1187–1191 (1987).

Article 
CAS 
PubMed 
PubMed Central 

Google Scholar
 

Tsay, P. K. et al. Impact of gender, viral transmission and aging in the prevalence of hepatitis B surface antigen. Chang Gung Med. J. 32, 155–164 (2009).

PubMed 

Google Scholar
 

Wang, S. H. et al. Estrogen receptor α represses transcription of HBV genes via interaction with hepatocyte nuclear factor 4α. Gastroenterology 142, 989–998 (2012).

Article 
CAS 
PubMed 

Google Scholar
 

Wu, M. H. et al. Androgen receptor promotes hepatitis B virus-induced hepatocarcinogenesis through modulation of hepatitis B virus RNA transcription. Sci. Transl. Med. 2, 32ra35 (2010).

Article 
PubMed 
PubMed Central 

Google Scholar
 

Naugler, W. E. et al. Gender disparity in liver cancer due to sex differences in MyD88-dependent IL-6 production. Science 317, 121–124 (2007).

Article 
CAS 
PubMed 

Google Scholar
 

Xu, C. et al. Sex differences in genomic features of hepatitis B–associated hepatocellular carcinoma with distinct antitumor immunity. Cell. Mol. Gastroenterol. Hepatol. 15, 327–354 (2023).

Article 
CAS 
PubMed 

Google Scholar
 

Klein, S. L, Pekosz, A, Passaretti, C, Anker, M & Olukoya, P. Sex, Gender and Influenza (World Health Organization: 2010).

Quandelacy, T. M., Viboud, C., Charu, V., Lipsitch, M. & Goldstein, E. Age- and sex-related risk factors for influenza-associated mortality in the United States between 1997–2007. Am. J. Epidemiol. 179, 156–167 (2014).

Article 
PubMed 

Google Scholar
 

Robinson, D. P., Lorenzo, M. E., Jian, W. & Klein, S. L. Elevated 17β-estradiol protects females from influenza a virus pathogenesis by suppressing inflammatory responses. PLoS Pathog. 7, e1002149 (2011).

Article 
CAS 
PubMed 
PubMed Central 

Google Scholar
 

Lorenzo, M. E. et al. Antibody responses and cross protection against lethal influenza A viruses differ between the sexes in C57BL/6 mice. Vaccine 29, 9246–9255 (2011).

Article 
CAS 
PubMed 
PubMed Central 

Google Scholar
 

Creisher, P. S., Seddu, K., Mueller, A. L. & Klein, S. L. in Sex and Gender Differences in Infection and Treatments for Infectious Diseases (eds. Klein, S. L. et al.) 111–137 (Springer International, 2023).

Vermillion, M. S. et al. Production of amphiregulin and recovery from influenza is greater in males than females. Biol. Sex Differ. 9, 24 (2018).

Article 
PubMed 
PubMed Central 

Google Scholar
 

Larcombe, A. N. et al. Sexual dimorphism in lung function responses to acute influenza A infection. Influenza Other Respir. Viruses 5, 334–342 (2011).

Article 
PubMed 
PubMed Central 

Google Scholar
 

Robinson, D. P., Hall, O. J., Nilles, T. L., Bream, J. H. & Klein, S. L. 17β-estradiol protects females against influenza by recruiting neutrophils and increasing virus-specific CD8 T cell responses in the lungs. J. Virol. 88, 4711–4720 (2014).

Article 
PubMed 
PubMed Central 

Google Scholar
 

Hall, O. J. et al. Progesterone-based therapy protects against influenza by promoting lung repair and recovery in females. PLoS Pathog. 12, e1005840 (2016).

Article 
PubMed 
PubMed Central 

Google Scholar
 

Creisher, P. S. et al. Suppression of progesterone by influenza A virus mediates adverse maternal and fetal outcomes in mice. mBio 15, e03065-03023 (2024).

Article 

Google Scholar
 

vom Steeg, L. G. et al. Androgen receptor signaling in the lungs mitigates inflammation and improves the outcome of influenza in mice. PLoS Pathog. 16, e1008506 (2020).

Article 
CAS 
PubMed 
PubMed Central 

Google Scholar
 

Huckestein, B. R. et al. Sex-based differences in persistent lung inflammation following influenza infection of juvenile outbred mice. Am. J. Physiol. Lung Cell. Mol. Physiol. 327, L189–L202 (2024).

Article 
CAS 
PubMed 
PubMed Central 

Google Scholar
 

Wang, C. et al. Sex disparities in influenza: a multiscale network analysis. iScience 25, 104192 (2022).

Article 
CAS 
PubMed 
PubMed Central 

Google Scholar
 

Fernandez-de-Las-Penas, C. et al. Symptoms experienced at the acute phase of SARS-CoV-2 infection as risk factor of long-term post-COVID symptoms: the LONG-COVID-EXP-CM multicenter study. Int. J. Infect. Dis. 116, 241–244 (2022).

Article 
CAS 
PubMed 
PubMed Central 

Google Scholar
 

Dhakal, S. et al. Sex differences in lung imaging and SARS-CoV-2 antibody responses in a COVID-19 golden Syrian hamster model. mBio 12, e0097421 (2021).

Article 
PubMed 
PubMed Central 

Google Scholar
 

Ruiz-Bedoya, C. A. et al. 124I-Iodo-DPA-713 positron emission tomography in a hamster model of SARS-CoV-2 infection. Mol. Imaging Biol. 24, 135–143 (2022).

Article 
CAS 
PubMed 

Google Scholar
 

Takahashi, T. et al. Sex differences in immune responses that underlie COVID-19 disease outcomes. Nature 588, 315–320 (2020). This study provides one of the first detailed analyses of sex differences in the immune profile of individuals with COVID-19, demonstrating how immunological differences between the sexes correlate with distinct acute disease outcomes.

Article 
CAS 
PubMed 
PubMed Central 

Google Scholar
 

Montaño Mendoza, V. M. et al. Biological sex and age-related differences shape the antiviral response to SARS-CoV-2 infection. Heliyon 9, e13045 (2023).

Article 
PubMed 
PubMed Central 

Google Scholar
 

Qin, L. et al. Gendered effects on inflammation reaction and outcome of COVID-19 patients in Wuhan. J. Med. Virol. 92, 2684–2692 (2020).

Article 
CAS 
PubMed 
PubMed Central 

Google Scholar
 

Scully, E. P. et al. Sex and gender differences in testing, hospital admission, clinical presentation, and drivers of severe outcomes from COVID-19. Open Forum Infect. Dis. 8, ofab448 (2021).

Article 
PubMed 
PubMed Central 

Google Scholar
 

Qu, H. Q., Glessner, J. T., Kao, C. & Hakonarson, H. Data-informed insights into sex differences in peripheral blood mononuclear cells from single-cell transcriptomics. Genes Dis. 12, 101525 (2025).

Article 
CAS 
PubMed 
PubMed Central 

Google Scholar
 

Sauerwald, N. et al. Pre-infection antiviral innate immunity contributes to sex differences in SARS-CoV-2 infection. Cell Syst. 13, 924–931 (2022).

Article 
CAS 
PubMed 
PubMed Central 

Google Scholar
 

Agrawal, S., Salazar, J., Tran, T. M. & Agrawal, A. Sex-related differences in innate and adaptive immune responses to SARS-CoV-2. Front. Immunol. 12, 739757 (2021).

Article 
CAS 
PubMed 
PubMed Central 

Google Scholar
 

Masters, E. A. et al. Dissecting sex-specific pathology in K18-hACE2 transgenic mice infected with different SARS-CoV-2 variants. J. Med. Virol. 97, e70506 (2025).

Article 
CAS 
PubMed 
PubMed Central 

Google Scholar
 

Gupta, M., Srikrishna, G., Klein, S. L. & Bishai, W. R. Genetic and hormonal mechanisms underlying sex-specific immune responses in tuberculosis. Trends Immunol. 43, 640–656 (2022).

Article 
CAS 
PubMed 
PubMed Central 

Google Scholar
 

Bini, E. I. et al. The influence of sex steroid hormones in the immunopathology of experimental pulmonary tuberculosis. PLoS ONE 9, e93831 (2014).

Article 
PubMed 
PubMed Central 

Google Scholar
 

Dibbern, J., Eggers, L. & Schneider, B. E. Sex differences in the C57BL/6 model of Mycobacterium tuberculosis infection. Sci. Rep. 7, 10957 (2017).

Article 
PubMed 
PubMed Central 

Google Scholar
 

Hertz, D. et al. Turning the tables: loss of adaptive immunity reverses sex differences in tuberculosis. Immuno 5, 4 (2025).

Article 

Google Scholar
 

Corica, B., Tartaglia, F., D’Amico, T., Romiti, G. F. & Cangemi, R. Sex and gender differences in community-acquired pneumonia. Intern. Emerg. Med. 17, 1575–1588 (2022).

Article 
PubMed 
PubMed Central 

Google Scholar
 

Lopez-de-Andres, A. et al. Gender differences in incidence and in-hospital outcomes of community-acquired, ventilator-associated and nonventilator hospital-acquired pneumonia in Spain. Int. J. Clin. Pract. 75, e13762 (2021).

Article 
PubMed 

Google Scholar
 

Kadioglu, A. et al. Sex-based differences in susceptibility to respiratory and systemic pneumococcal disease in mice. J. Infect. Dis. 204, 1971–1979 (2011).

Article 
CAS 
PubMed 

Google Scholar
 

Xiong, Y. et al. Estradiol resolves pneumonia via ERbeta in regulatory T cells. JCI Insight 6, e133251 (2021).

Article 
PubMed 
PubMed Central 

Google Scholar
 

Yang, Z. et al. Female resistance to pneumonia identifies lung macrophage nitric oxide synthase-3 as a therapeutic target. eLife 3 (2014). This study demonstrates that estrogen drives NOS3 activation in lung macrophages, revealing a sex-specific protective pathway that underlie differential responses to pneumococcal pneumonia and highlighting NOS3 as a potential therapeutic target for treating infections.

Abid, S. et al. 17β-estradiol dysregulates innate immune responses to pseudomonas aeruginosa respiratory infection and is modulated by estrogen receptor antagonism. Infect. Immun. 85, e00422–17 (2017).

Article 
CAS 
PubMed 
PubMed Central 

Google Scholar
 

Pires, S., Peignier, A., Seto, J., Smyth, D. S. & Parker, D. Biological sex influences susceptibility to Acinetobacter baumannii pneumonia in mice. JCI Insight 5, e132223 (2020).

Article 
PubMed 
PubMed Central 

Google Scholar
 

Linz, M. S. et al. Biological sex influences severity and outcomes in Acinetobacter baumannii pneumonia. Microbiol. Spectr. 13, e0319924 (2025).

Article 
PubMed 
PubMed Central 

Google Scholar
 

Wang, Y., Cela, E., Gagnon, S. & Sweezey, N. B. Estrogen aggravates inflammation in Pseudomonas aeruginosa pneumonia in cystic fibrosis mice. Respir. Res. 11, 166 (2010).

Article 
CAS 
PubMed 
PubMed Central 

Google Scholar
 

Turner, J. R. Intestinal mucosal barrier function in health and disease. Nat. Rev. Immunol. 9, 799–809 (2009).

Article 
CAS 
PubMed 

Google Scholar
 

Sankaran-Walters, S. et al. Sex differences matter in the gut: effect on mucosal immune activation and inflammation. Biol. Sex Differ. 4, 10 (2013).

Article 
PubMed 
PubMed Central 

Google Scholar
 

Goodman, W. A. et al. Impaired estrogen signaling underlies regulatory T cell loss-of-function in the chronically inflamed intestine. Proc. Natl Acad. Sci. USA 117, 17166–17176 (2020).

Article 
CAS 
PubMed 
PubMed Central 

Google Scholar
 

Homma, H. et al. The female intestine is more resistant than the male intestine to gut injury and inflammation when subjected to conditions associated with shock states. Am. J. Physiol. Gastrointest. Liver Physiol. 288, G466–G472 (2005).

Article 
CAS 
PubMed 

Google Scholar
 

Eggleston, F. C., Santoshi, B. & Singh, C. M. Typhoid perforation of the bowel experiences in 78 cases. Ann. Surg. 190, 31–35 (1979).

Article 
CAS 
PubMed 
PubMed Central 

Google Scholar
 

Ferro, A. et al. Sex differences in the prevalence of Helicobacter pylori infection: an individual participant data pooled analysis (StoP Project). Eur. J. Gastroenterol. Hepatol. 31, 593–598 (2019).

Article 
PubMed 

Google Scholar
 

Ohtani, M. et al. 17 beta-estradiol suppresses Helicobacter pylori-induced gastric pathology in male hypergastrinemic INS-GAS mice. Carcinogenesis 32, 1244–1250 (2011).

Article 
CAS 
PubMed 
PubMed Central 

Google Scholar
 

Deltourbe, L., Lacerda Mariano, L., Hreha, T. N., Hunstad, D. A. & Ingersoll, M. A. The impact of biological sex on diseases of the urinary tract. Mucosal Immunol. 15, 857–866 (2022).

Article 
CAS 
PubMed 
PubMed Central 

Google Scholar
 

Olson, P. D., Hruska, K. A. & Hunstad, D. A. Androgens enhance male urinary tract infection severity in a new model. J. Am. Soc. Nephrol. 27, 1625–1634 (2016).

Article 
CAS 
PubMed 

Google Scholar
 

Olson, P. D. et al. Androgen exposure potentiates formation of intratubular communities and renal abscesses by Escherichia coli. Kidney Int. 94, 502–513 (2018).

Article 
CAS 
PubMed 
PubMed Central 

Google Scholar
 

Trautmann, A. Core features and inherent diversity of post-acute infection syndromes. Front. Immunol. 16, 1509131 (2025).

Article 
CAS 
PubMed 
PubMed Central 

Google Scholar
 

Johnson, D. & Jiang, W. Infectious diseases, autoantibodies, and autoimmunity. J. Autoimmun. 137, 102962 (2023).

Article 
CAS 
PubMed 

Google Scholar
 

Sylvester, S. V. et al. Sex differences in sequelae from COVID-19 infection and in long COVID syndrome: a review. Curr. Med. Res. Opin. 38, 1391–1399 (2022).

Article 
CAS 
PubMed 

Google Scholar
 

Gorenshtein, A., Leibovitch, L., Liba, T., Stern, S. & Stern, Y. Gender disparities in neurological symptoms of long COVID: a systematic review and meta-analysis. Neuroepidemiology 59, 426–440 (2025).

Article 
PubMed 

Google Scholar
 

Moldofsky, H. & Patcai, J. Chronic widespread musculoskeletal pain, fatigue, depression and disordered sleep in chronic post-SARS syndrome; a case-controlled study. BMC Neurol. 11, 37 (2011).

Article 
PubMed 
PubMed Central 

Google Scholar
 

Tansey, C. M. et al. One-year outcomes and health care utilization in survivors of severe acute respiratory syndrome. Arch. Intern. Med. 167, 1312–1320 (2007).

Article 
PubMed 

Google Scholar
 

Wu, X., Dong, D. & Ma, D. Thin-section computed tomography manifestations during convalescence and long-term follow-up of patients with severe acute respiratory syndrome (SARS). Med. Sci. Monit. 22, 2793–2799 (2016).

Article 
PubMed 
PubMed Central 

Google Scholar
 

Lee, S. H. et al. Depression as a mediator of chronic fatigue and post-traumatic stress symptoms in Middle East respiratory syndrome survivors. Psychiatry Investig. 16, 59–64 (2019).

PubMed 
PubMed Central 

Google Scholar
 

Spetz, M., Natt Och Dag, Y., Li, H., Nyberg, F. & Rosvall, M. Covid-19 and cardiovascular disease in a total population-study of long-term effects, social factors and Covid-19-vaccination. Nat. Commun. 16, 10115 (2025).

Article 
CAS 
PubMed 
PubMed Central 

Google Scholar
 

Hamlin, R. E. et al. Sex differences and immune correlates of Long Covid development, symptom persistence, and resolution. Sci. Transl. Med. 16, eadr1032 (2024). The authors characterize sex-specific immune dysregulation using multi-omics profiling of immune cells from SARS-CoV-2-infected patients that either recover or develop long COVID. They identify sex differences in acute and persistent immune transcriptional responses and sex chromosome gene expression that may contribute to the higher risk of long COVID in female individuals.

Article 
CAS 
PubMed 
PubMed Central 

Google Scholar
 

Fulton, C. D., Beasley, D. W., Bente, D. A. & Dineley, K. T. Long-term, West Nile virus-induced neurological changes: a comparison of patients and rodent models. Brain Behav. Immun. Health 7, 100105 (2020).

Article 
PubMed 
PubMed Central 

Google Scholar
 

Hoffman, K. W. et al. Sex differences in cytokine production following West Nile virus infection: implications for symptom manifestation. Pathog. Dis. 77, ftz016 (2019).

Article 
CAS 
PubMed 
PubMed Central 

Google Scholar
 

Lim, J. T. et al. Characterization of post-acute multi-organ sequelae following dengue infection. Clin. Microbiol. Infect. 31, 1865–1872 (2025).

Article 
CAS 
PubMed 

Google Scholar
 

García, G. et al. Long-term persistence of clinical symptoms in dengue-infected persons and its association with immunological disorders. Int. J. Infect. Dis. 15, e38–e43 (2011).

Article 
PubMed 

Google Scholar
 

Hertanti, N. S., Nguyen, T. V. & Chuang, Y.-H. Global prevalence and risk factors of fatigue and post-infectious fatigue among patients with dengue: a systematic review and meta-analysis. EClinicalMedicine 80, 103041 (2025).

Article 
PubMed 

Google Scholar
 

Seet, R. C., Quek, A. M. & Lim, E. C. Post-infectious fatigue syndrome in dengue infection. J. Clin. Virol. 38, 1–6 (2007).

Article 
PubMed 

Google Scholar
 

Lazari, C. D. S. et al. Clinical markers of post-Chikungunya chronic inflammatory joint disease: a Brazilian cohort. PLoS Negl. Trop. Dis. 17, e0011037 (2023).

Article 
PubMed 
PubMed Central 

Google Scholar
 

Ramachandran, V. et al. Impact of Chikungunya on health related quality of life Chennai, South India. PLoS ONE 7, e51519 (2012).

Article 
CAS 
PubMed 
PubMed Central 

Google Scholar
 

Bjornevik, K. et al. Longitudinal analysis reveals high prevalence of Epstein-Barr virus associated with multiple sclerosis. Science 375, 296–301 (2022).

Article 
CAS 
PubMed 

Google Scholar
 

Younis, S. et al. Epstein-Barr virus reprograms autoreactive B cells as antigen-presenting cells in systemic lupus erythematosus. Sci. Transl. Med. 17, eady0210 (2025).

Article 
CAS 
PubMed 
PubMed Central 

Google Scholar
 

Wormser, G. P. & Shapiro, E. D. Implications of gender in chronic Lyme disease. J. Womens Health 18, 831–834 (2009).

Article 

Google Scholar
 

Rebman, A. W., Soloski, M. J. & Aucott, J. N. in Sex and Gender Differences in Infection and Treatments for Infectious Diseases (eds Klein, S. L. & Roberts, C. W.) 337–360 (Springer, 2015).

Johnson, L., Shapiro, M., Janicki, S., Mankoff, J. & Stricker, R. B. Does biological sex matter in Lyme disease? The need for sex-disaggregated data in persistent illness. Int. J. Gen. Med. 16, 2557–2571 (2023).

Article 
PubMed 
PubMed Central 

Google Scholar
 

Aucott, J. N. et al. Risk of post-treatment Lyme disease in patients with ideally-treated early Lyme disease: a prospective cohort study. Int. J. Infect. Dis. 116, 230–237 (2022).

Article 
CAS 
PubMed 

Google Scholar
 

Girgis, A. A. et al. Aberrant T-cell phenotypes in a cohort of patients with post-treatment Lyme disease. Front. Immunol. 16, 1607619 (2025).

Article 
PubMed 
PubMed Central 

Google Scholar
 

Zinck, C. B. et al. Pathogen strain and host sex influence infection prevalence and tissue spirochete load of Borrelia burgdorferi in its rodent host. Mol. Ecol. 31, 5872–5888 (2022).

Article 
PubMed 
PubMed Central 

Google Scholar
 

Koloski, C. W. et al. Male C57BL/6J mice have higher presence and abundance of Borrelia burgdorferi in their ventral skin compared to female mice. Ticks Tick Borne Dis. 15, 102308 (2024).

Article 
PubMed 

Google Scholar
 

Brouqui, P. et al. Chronic Q fever: ninety-two cases from France, including 27 cases without endocarditis. Arch. Intern. Med. 153, 642–648 (1993).

Article 
CAS 
PubMed 

Google Scholar
 

Textoris, J. et al. Sex-related differences in gene expression following Coxiella burnetii infection in mice: potential role of circadian rhythm. PLoS ONE 5, e12190 (2010).

Article 
PubMed 
PubMed Central 

Google Scholar
 

Gay, L. et al. Impact of sex hormones on macrophage responses to Coxiella burnetii. Front. Immunol. 12, 705088 (2021).

Article 
CAS 
PubMed 
PubMed Central 

Google Scholar
 

Dominguez, A. et al. Seroprevalence of measles, rubella, and mumps antibodies in Catalonia, Spain: results of a cross-sectional study. Eur. J. Clin. Microbiol. Infect. Dis. 25, 310–317 (2006).

Article 
CAS 
PubMed 

Google Scholar
 

Mossong, J., O’Callaghan, C. J. & Ratnam, S. Modelling antibody response to measles vaccine and subsequent waning of immunity in a low exposure population. Vaccine 19, 523–529 (2001).

Article 

Google Scholar
 

Riggenbach, M. M. et al. Mumps virus-specific immune response outcomes and sex-based differences in a cohort of healthy adolescents. Clin. Immunol. 234, 108912 (2022).

Article 
CAS 
PubMed 

Google Scholar
 

Hoes, J. et al. Comparison of antibody response between boys and girls after infant and childhood vaccinations in the Netherlands. Vaccine 37, 4504–4510 (2019).

Article 
CAS 
PubMed 

Google Scholar
 

Aldakak, L., Huber, V. M., Ruhli, F. & Bender, N. Sex difference in the immunogenicity of the quadrivalent human papilloma virus vaccine: systematic review and meta-analysis. Vaccine 39, 1680–1686 (2021).

Article 
CAS 
PubMed 

Google Scholar
 

Engler, R. J. et al. Half- vs full-dose trivalent inactivated influenza vaccine (2004–2005): age, dose, and sex effects on immune responses. Arch. Intern. Med. 168, 2405–2414 (2008).

Article 
PubMed 

Google Scholar
 

Furman, D. et al. Systems analysis of sex differences reveals an immunosuppressive role for testosterone in the response to influenza vaccination. Proc. Natl Acad. Sci. USA 111, 869–874 (2014).

Article 
CAS 
PubMed 

Google Scholar
 

Nguyen, D. C. et al. 17β-estradiol restores antibody responses to an influenza vaccine in a postmenopausal mouse model. Vaccine 29, 2515–2518 (2011).

Article 
CAS 
PubMed 

Google Scholar
 

Pauklin, S., Sernandez, I. V., Bachmann, G., Ramiro, A. R. & Petersen-Mahrt, S. K. Estrogen directly activates AID transcription and function. J. Exp. Med. 206, 99–111 (2009).

Article 
CAS 
PubMed 
PubMed Central 

Google Scholar
 

Demonbreun, A. R. et al. COVID-19 mRNA vaccination generates greater IgG levels in women compared to men. J. Infect. Dis. 224, 793–797 (2021).

Article 
CAS 
PubMed 
PubMed Central 

Google Scholar
 

Visci, G. et al. Serological response after SARS-CoV-2 vaccination in healthcare workers: a multicenter study. Med. Lav. 113, e2022022 (2022).

PubMed 
PubMed Central 

Google Scholar
 

Kageyama, T. et al. Antibody responses to BNT162b2 mRNA COVID-19 vaccine and their predictors among healthcare workers in a tertiary referral hospital in Japan. Clin. Microbiol. Infect. 27, 1861–1865 (2021).

Article 

Google Scholar
 

Shapiro, J. R. et al. Association of frailty, age, and biological sex with SARS-CoV-2 mRNA vaccine-induced immunity in older adults. Clin. Infect. Dis. 75, S61–S71 (2022).

Article 
PubMed 
PubMed Central 

Google Scholar
 

Lustig, Y. et al. BNT162b2 COVID-19 vaccine and correlates of humoral immune responses and dynamics: a prospective, single-centre, longitudinal cohort study in health-care workers. Lancet Respir. Med. 9, 999–1009 (2021).

Article 
CAS 
PubMed 
PubMed Central 

Google Scholar
 

Notarte, K. I. et al. Effects of age, sex, serostatus, and underlying comorbidities on humoral response post-SARS-CoV-2 Pfizer-BioNTech mRNA vaccination: a systematic review. Crit. Rev. Clin. Lab. Sci. 59, 373–390 (2022).

Article 
CAS 
PubMed 
PubMed Central 

Google Scholar
 

Tong, S. et al. COVID-19 mRNA or viral vector vaccine type and subject sex influence the SARS-CoV-2 T-cell response. Vaccine 61, 127420 (2025).

Article 
CAS 
PubMed 

Google Scholar
 

Levin, E. G. et al. Waning immune humoral response to BNT162b2 COVID-19 vaccine over 6 months. N. Engl. J. Med. 385, e84 (2021).

Article 
CAS 
PubMed 
PubMed Central 

Google Scholar
 

Oyebanji, O. A. et al. COVID-19 booster doses reduce sex disparities in antibody responses among nursing home residents. Clin. Exp. Res. 37, 73 (2025).


Google Scholar
 

Chaulagain, S. et al. COVID-19 vaccine (NVX-CoV2373 and NVX-CoV2540) doses and virus strain match impact sex- and age-specific immunity and protection in mice. Vaccine 61, 127409 (2025).

Article 
CAS 
PubMed 
PubMed Central 

Google Scholar
 

Sparks, R. et al. Influenza vaccination reveals sex dimorphic imprints of prior mild COVID-19. Nature 614, 752–761 (2023).

Article 
CAS 
PubMed 
PubMed Central 

Google Scholar
 

Taquet, M., Dercon, Q., Todd, J. A. & Harrison, P. J. The recombinant shingles vaccine is associated with lower risk of dementia. Nat. Med. 30, 2777–2781 (2024).

Article 
CAS 
PubMed 
PubMed Central 

Google Scholar
 

St Clair, L. A., Chaulagain, S., Klein, S. L., Benn, C. S. & Flanagan, K. L. Sex-differential and non-specific effects of vaccines over the life course. Curr. Top Microbiol. Immunol. 441, 225–251 (2023).


Google Scholar
 

Roth, A. et al. Tuberculin reaction, BCG scar, and lower female mortality. Epidemiology 17, 562–568 (2006).

Article 
PubMed 

Google Scholar
 

Harikumar Parvathy, G. et al. Sex differences in vaccine-induced immunity and protection against Mycobacterium tuberculosis. J. Infect. Dis. 232, 1187–1197 (2025).

Article 
CAS 
PubMed 

Google Scholar
 

Nieuwenhuizen, N. E. et al. Weaker protection against tuberculosis in BCG-vaccinated male 129 S2 mice compared to females. Vaccine 39, 7253–7264 (2021).

Article 
CAS 
PubMed 

Google Scholar
 

Cook, I. F. Sexual dimorphism of humoral immunity with human vaccines. Vaccine 26, 3551–3555 (2008).

Article 
CAS 
PubMed 

Google Scholar
 

Chiarella, S. E., Jenkins, S. M., Park, M. A., Abraham, R. S. & Joshi, A. Y. Sex differences in antibody responses to the 23-valent pneumococcal polysaccharide vaccination. Ann. Allergy Asthma Immunol. 127, 509–510 (2021).

Article 
CAS 
PubMed 
PubMed Central 

Google Scholar
 

Ravichandran, S. et al. Distinct baseline immune characteristics associated with responses to conjugated and unconjugated pneumococcal polysaccharide vaccines in older adults. Nat. Immunol. 25, 316–329 (2024). This study examines how preexisting immune landscapes in older men and wmomen influence responses to two FDA-approved pneumococcal vaccines, providing a foundation for precision vaccination strategies in aging populations.

Article 
CAS 
PubMed 
PubMed Central 

Google Scholar
 

Tchalla, E. Y. I., Betadpur, A., Khalil, A. Y., Bhalla, M. & Bou Ghanem, E. N. Sex-based difference in immune responses and efficacy of the pneumococcal conjugate vaccine. J. Leukoc. Biol. 117, qiae177 (2024).

Article 
PubMed 
PubMed Central 

Google Scholar
 

Scully, E. P., Morgan, R. & Klein, S. L. Precision vaccinology: making vaccines work better for women and men. J. Infect. Dis. 232, 756–759 (2025).

Article 
PubMed 
PubMed Central 

Google Scholar