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Updated: Jul 5, 2025
A High-throughput Shigella-specific Bactericidal Assay
Published on: February 27, 2019
Molecular Signature of Monocytes Shaped by the Shigella sonnei 1790-Generalized Modules for Membrane Antigens Vaccine
Serena Tondi1,2, Emilio Siena1, Ahmed Essaghir1
1Preclinical Research & Development, GSK, 53100 Siena, Italy.
Abstract:
Shigellosis, an acute gastroenteritis infection caused by Shigella species, remains a public health burden in developing countries. Recently, many outbreaks due to Shigella sonnei multidrug-resistant strains have been reported in high-income countries, and the lack of an effective vaccine represents a major hurdle to counteract this bacterial pathogen. Vaccine candidates against Shigella sonnei are under clinical development, including a Generalized Modules for Membrane Antigens (GMMA)-based vaccine. The mechanisms by which GMMA-based vaccines interact and activate human immune cells remain elusive. Our previous study provided the first evidence that both adaptive and innate immune cells are targeted and functionally shaped by the GMMA-based vaccine. Here, flow cytometry and confocal microscopy analysis allowed us to identify monocytes as the main target population interacting with the S. sonnei 1790-GMMA vaccine on human peripheral blood. In addition, transcriptomic analysis of this cell population revealed a molecular signature induced by 1790-GMMA mostly correlated with the inflammatory response and cytokine-induced processes. This also impacts the expression of genes associated with macrophages' differentiation and T cell regulation, suggesting a dual function for this vaccine platform both as an antigen carrier and as a regulator of immune cell activation and differentiation.
Insights
Generalized Modules for Membrane Antigens (GMMA)-based vaccines target monocytes, initiating inflammatory responses and influencing immune cell differentiation. This research sheds light on GMMA vaccine mechanisms against Shigella sonnei.
Area of Science:
- Immunology
- Vaccinology
- Microbiology
Background:
- Shigellosis, caused by Shigella, is a significant public health issue, particularly with emerging multidrug-resistant strains.
- The absence of an effective Shigella sonnei vaccine hinders control efforts, despite ongoing clinical development.
- Generalized Modules for Membrane Antigens (GMMA)-based vaccines are promising candidates, but their interaction with human immune cells requires elucidation.
Purpose of the Study:
- To investigate the immune cell populations targeted by a Shigella sonnei 1790-GMMA vaccine.
- To characterize the molecular mechanisms underlying the immune response induced by the GMMA vaccine.
Main Methods:
- Flow cytometry and confocal microscopy were used to identify immune cell interactions with the S. sonnei 1790-GMMA vaccine.
- Transcriptomic analysis was performed on targeted immune cells to understand molecular responses.
Main Results:
- Monocytes were identified as the primary immune cells interacting with the S. sonnei 1790-GMMA vaccine in human peripheral blood.
- Transcriptomic analysis revealed that the vaccine induces a molecular signature associated with inflammatory and cytokine-related processes.
- The vaccine impacts gene expression linked to macrophage differentiation and T cell regulation.
Conclusions:
- The S. sonnei 1790-GMMA vaccine engages monocytes, driving inflammatory responses and influencing immune cell differentiation pathways.
- This suggests a dual role for GMMA-based vaccines as antigen carriers and modulators of immune cell activation.
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