Integration of Immune Responses and Transcriptomic Signatures Reveals the Efficacy of Maternal Genetic Vaccination in a Pregnant Model and Its Neonates

Maternal vaccination is essential for safeguarding both mother and foetus from infectious diseases. This study investigated the immunogenicity and efficacy of a maternal ORF-B2L genetic vaccine in a pregnant rat model, focusing on maternal-neonatal immune modulation, placental and neonatal spleen transcriptomics and the underlying mechanisms contributing to neonatal immune development. Female rats received intramuscular injections of either a gene vaccine (GV) containing 200 μg of recombinant ORF-B2L DNA and 50 μg of a subunit protein or an empty plasmid as a control. Results showed significantly higher levels of specific anti-B2L antibodies and Th1 and Th2 cytokine levels in both maternal and neonatal sera from the GV group compared to the control group (p < 0.05). Transcriptome analysis identified 1295 differentially expressed genes (DEGs) in the placenta and 998 DEGs in the neonatal spleen, with upregulated pathways associated with immune cell recruitment, cytokine signalling and hormone regulation in the GV group. Notably, upregulated DEGs such as TLR4, ESR1 and various cytokine/chemokine-related genes in the placenta suggest enhanced immune regulation and foetal protection. In the neonatal spleen, increased expression of IL-1β, IL-6, IL-10 and CD69 indicates enhanced T and B cell development and pathogen defence. The upregulation of IL-1β suggests a Th1 response, while elevated IL-10 indicates a potential Th2-biased immunity, reflecting a balanced Th1/Th2 response that is crucial for effective adaptive immunity. Overall, maternal ORF-B2L genetic vaccination induces a robust immune response, enhancing maternal-foetal protection and shaping neonatal immune responses, offering valuable insights for optimizing maternal vaccination strategies.