Immunological Mechanisms of Sex Differences in Infectious Disease Outcomes and Vaccine Responses

Biological sex is a critical determinant of susceptibility, disease progression, and treatment outcomes in infectious diseases, driven primarily by fundamental differences in innate and adaptive immunity. Variations in genetic, epigenetic, and hormonal factors between males and females shape how immune cells develop, signal, and respond to pathogens and vaccines. Despite the growing recognition of sex-based immunological variation, molecular and cellular-level research remains scarce, particularly regarding infectious diseases prevalent in low- and middle-income countries (LMICs). The biological disparities governing these responses are highly dynamic and shift across the lifespan, where age-related physiological transitions fundamentally interact with sex-specific immune profiles.This Research Topic aims to consolidate mechanistic evidence exploring how biological sex shapes immune function in the context of infectious disease and immunization. We seek to understand the cellular and molecular pathways that translate sex-specific immune profiles into differential susceptibility, disease severity, and vaccine efficacy. Contributions must go beyond demographic associations to investigate the biological underpinnings of sex-based variation. Specifically, studies should address how sex steroid signaling, sex chromosome-linked genes, and age-related physiological shifts modulate immune responses.The Topic Editors welcome original research, systematic reviews, and perspectives focused on several key immunological themes:o Mechanistic Basis of Sex-Biased Immunity — Investigations into the hormonal, genetic, and epigenetic pathways, including sex chromosome-linked immune genes and incomplete X chromosome inactivation, that drive sex differences in immune cell development, phenotype, and function.o Sex-Differential Immune Responses to Pathogens — Cellular and molecular analyses of sex differences in innate and adaptive immunity during viral, bacterial, and parasitic infections, including neglected tropical diseases and co-infections.o Immunological Underpinnings of Vaccine Efficacy — Studies exploring sex-differential responses to vaccination, focusing on the biological mechanisms of vaccine immunogenicity, adjuvant reactogenicity, and protective efficacy across the lifespan.o Endocrine-Immune Interactions Across the Lifespan — Research on how puberty, pregnancy, and menopause or andropause alter sex steroid signaling in innate and adaptive immune cells to shape infectious disease susceptibility.To align with the scope of the Sex Differences in Immunology section, all submissions must provide detailed, mechanistic, or clinically relevant insights into how biological sex influences immune responses. Studies should include sex-disaggregated immunological analyses or directly compare male and female subjects at the cellular, molecular, or organismal level, with sex treated as a primary biological variable. Submissions reporting sex solely as a demographic or epidemiological variable without meaningful immunological analysis or mechanistic insight will not be considered.Please note that Djeneba Dabitao has been recently awarded funding from a private company based in the US to clinically evaluate an AI-based tool for diagnosis of infectious diseases in Mali.Please note that Santosh Dhakal has patents on swine influenza vaccines and has received grants to work on infectious diseases from private companies in the past. Topic editors: Djeneba Dabitao, Santosh Dhakal Source: https://www.frontiersin.org/research-topics/84000/immunological-mechanisms-of-sex-differences-in-infectious-disease-outcomes-and-vaccine-responses