Vaccines

The development of safe, effective, and durable vaccines remains a central goal in preventing infectious diseases in humans and animals [...]

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.

Background/Objectives: The rapid development of safe and efficacious vaccines is often hindered by extensive, mandated non-clinical safety evaluations in animals. With the aim to provide scientific evidence supporting a “vaccine platform approach”, here we present the complete non-clinical studies for two investigational vaccines, GRAd-COV2 and GRAdHIVNE1, based on GRAd, a gorilla-derived group C adenoviral vector. Methods: The biodistribution of GRAd genomes following the intramuscular administration of the vaccines was assessed in rats by a sensitive qPCR method. Local tolerance and systemic toxic effects were evaluated in single- and repeated-dose toxicity studies in rabbits. Results: GRAd-COV2 and GRAdHIVNE1 were well-tolerated. Distribution was highly confined to the injection site and draining lymph nodes, and toxicity profile consisted of transient, non-adverse inflammatory responses, while the expected immune responses to the encoded antigens were successfully induced. Notably, both vaccines demonstrated a consistent safety profile despite transgene and backbone differences, comparable to other replication-defective adenoviral vectors. Conclusions: The established non-clinical safety profile of the GRAd platform provides a robust foundation for a more efficient and streamlined regulatory pathway. By leveraging this prior knowledge, future GRAd-based vaccines can achieve accelerated clinical development while fully adhering to the ethical principles of replacement, reduction, and refinement of animal use in research.