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Comparative Systems Analyses Reveal Molecular Signatures of Clinically tested Vaccine Adjuvants
Thorunn A Olafsdottir1, Madelene Lindqvist1, Intawat Nookaew2,3
1Department of Microbiology and Immunology, Institute of Biomedicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
Abstract:
A better understanding of the mechanisms of action of human adjuvants could inform a rational development of next generation vaccines for human use. Here, we exploited a genome wide transcriptomics analysis combined with a systems biology approach to determine the molecular signatures induced by four clinically tested vaccine adjuvants, namely CAF01, IC31, GLA-SE and Alum in mice. We report signature molecules, pathways, gene modules and networks, which are shared by or otherwise exclusive to these clinical-grade adjuvants in whole blood and draining lymph nodes of mice. Intriguingly, co-expression analysis revealed blood gene modules highly enriched for molecules with documented roles in T follicular helper (TFH) and germinal center (GC) responses. We could show that all adjuvants enhanced, although with different magnitude and kinetics, TFH and GC B cell responses in draining lymph nodes. These results represent, to our knowledge, the first comparative systems analysis of clinically tested vaccine adjuvants that may provide new insights into the mechanisms of action of human adjuvants.
Insights
This study reveals molecular signatures of four vaccine adjuvants (CAF01, IC31, GLA-SE, Alum) in mice. All adjuvants boosted T follicular helper (TFH) and germinal center (GC) responses, offering insights into vaccine mechanisms.
Area of Science:
- Immunology
- Vaccinology
- Systems Biology
Background:
- Understanding vaccine adjuvant mechanisms is crucial for developing next-generation vaccines.
- Four clinically tested adjuvants (CAF01, IC31, GLA-SE, Alum) were analyzed.
- Previous research lacked comparative systems-level analysis of these adjuvants.
Purpose of the Study:
- To determine the molecular signatures induced by four clinically tested vaccine adjuvants in mice.
- To identify shared and exclusive molecular pathways, gene modules, and networks.
- To elucidate the mechanisms of action of human vaccine adjuvants.
Main Methods:
- Genome-wide transcriptomics analysis in mice.
- Systems biology approach to analyze molecular signatures.
- Co-expression analysis of whole blood and draining lymph node samples.
Main Results:
- Identified distinct and shared molecular signatures for CAF01, IC31, GLA-SE, and Alum.
- Discovered blood gene modules enriched for T follicular helper (TFH) and germinal center (GC) response molecules.
- Confirmed that all adjuvants enhanced TFH and GC B cell responses in draining lymph nodes with varying kinetics and magnitude.
Conclusions:
- This comparative systems analysis provides novel insights into the mechanisms of action of clinically relevant vaccine adjuvants.
- The findings highlight the role of TFH and GC responses in adjuvant-induced immunomodulation.
- Results pave the way for rational design of improved vaccine formulations.
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