# Advances in Spatial Transcriptomics for Infectious Disease Research: Insight for Vaccine Development

## TL;DR

Spatial transcriptomics helps study how infections affect tissues, offering new insights for vaccine development by mapping gene activity in intact tissues.

## Contribution

The paper reviews how spatial transcriptomics is transforming infectious disease research and vaccine design by revealing tissue-specific immune responses.

## Key findings

- Spatial transcriptomics reveals immune responses and pathogen niches in viral, bacterial, and parasitic infections.
- The technology identifies tissue-specific immune programs and protective microenvironments relevant to vaccine development.
- Current ST platforms offer either whole-transcriptome coverage at modest resolution or high-resolution imaging with targeted genes.

## Abstract

Spatial transcriptomics (ST) enables genome-wide gene expression profiling while preserving tissue architecture, bridging the gap between bulk, single-cell, and histological analyses. Originating in 2016 and rapidly evolving since, ST has transformed infectious disease research by mapping host–pathogen interactions directly within intact tissues. Current platforms fall into two categories: sequencing-based methods (Visium, GeoMx, Stereo-seq) offering whole-transcriptome coverage at modest resolution and imaging-based platforms (Xenium, CosMx, MERFISH) providing single-cell or subcellular detail with targeted gene panels. These technologies reveal spatially organized immune responses, local tissue remodeling, and pathogen niches across viruses, bacteria, and parasites. In viral infection, ST uncovered heterogeneity in COVID-19 lung microenvironments, spatial immune activation in lymphoid tissues, and variant-specific inflammatory patterns. In bacterial disease, ST delineated granuloma architecture in tuberculosis and mapped vaccine-induced lung responses in Shigella studies. Parasitic infection studies identified localized inflammatory hotspots and microenvironmental control of T-cell differentiation in malaria. Despite powerful insights, ST faces constraints including RNA quality limitations, tradeoffs between resolution and transcript breadth, high cost, and analytical complexity. Nonetheless, ST increasingly informs vaccine design by identifying tissue-specific immune programs and protective microenvironments and is poised to become a standard tool for infectious disease biology.