B3696 - Impact of immune sex differences in the first 1000 days of life - 12/01/2021

B number: 
Principal applicant name: 
Matthew Suderman | University of Bristol (United Kingdom)
Philip Goulder, Professor
Title of project: 
Impact of immune sex differences in the first 1000 days of life
Proposal summary: 

Substantial differences exist between the immune reponses made by males and females that critically impact health and survival. Typically, females make stronger immune responses to vaccines and infections and achieve superior outcomes throughout life. For example, females achieve the same levels of neutralizing antibodies from half the dose of influenza vaccine as males from the full dose. However, this more exuberant immune response leads to greater susceptibility to immunopathology and autoimmune diseases and more adverse events from immunizations. To complicate matters, there are exceptions; as fetuses, females have a 2-fold greater susceptibility to mother-to-child transmission of both HIV and HCV infection, and to IFN-I-resistant viruses. To better understand the mechanisms responsible for these complex observations, we propose to compare the epigenetic and hormonal responses in males and females to immunization and vaccination in early life. We hypothesize that life-long immune sex differences are established early through the interplay of host genetics, sex-specific steroid biosynthesis, epigenetics and the environment, and that early-life epigenetic changes in response to sex-specific steroid modulation and infection and immunization play a dominant role in this process.

Impact of research: 
In the short-term, we hope to better understand the mechanism responsible for sex-specific immune responses. In the long-term, improved understanding of these mechanisms should provide the rationale to tailor vaccines and treatments and improve patient outcomes.
Date proposal received: 
Thursday, 7 January, 2021
Date proposal approved: 
Tuesday, 12 January, 2021
Immunology, Infection, Microarrays, Proteomics, Biological samples -e.g. blood, cell lines, saliva, etc., Biomarkers - e.g. cotinine, fatty acids, haemoglobin, etc., Environment - enviromental exposure, pollution, Epigenetics, Immunity, Sex differences