Multi-Omics Analysis Reveals Sex-Specific Signatures for BCG Vaccine Efficacy

Area of Science:

• Immunology
• Vaccinology
• Genomics

Background:

• Vaccine efficacy varies significantly between individuals.
• The Bacille Calmette-Guérin (BCG) vaccine's effectiveness is influenced by factors like sex, age, and location.
• Limited research exists on sex-specific immune determinants of vaccine efficacy using multi-omics data.

Purpose of the Study:

• To investigate sex-specific immune responses to the BCG vaccine.
• To identify biological factors influencing BCG vaccine efficacy using multi-omics data.
• To explore potential strategies for optimizing vaccine effectiveness based on sex-specific immune profiles.

Main Methods:

• Analysis of multi-omics data from 321 healthy individuals vaccinated with BCG.
• Integration of immune cell frequencies, single-cell RNA sequencing, plasma proteins, metabolites, and DNA methylation profiles.
• Comparative analysis of pre-vaccination immune signatures between biological sexes.

Main Results:

• Significant sex-specific differences were observed in immune pathways related to BCG efficacy.
• Males showed pre-vaccination signatures associated with a stronger pro-inflammatory and innate immune response.
• Females exhibited enhanced antigen presentation pathways and adaptive immune responses post-vaccination.

Conclusions:

• Biological sex plays a crucial role in modulating immune responses to the BCG vaccine.
• Understanding individual baseline immune status in relation to sex is vital for improving vaccine effectiveness.
• Sex-specific immunological insights offer a promising avenue for personalized vaccine strategies.