Meta-análise transcricional de indivíduos vacinados contra malária

Abstract

Malaria causes over 600,000 deaths annually, with the vast majority of fatalities resulting from Plasmodium falciparum infection. This disease remains a major humanitarian problem across tropical regions of the world, particularly in sub-Saharan Africa, where most deaths occur among pregnant women, newborns, and children under five. Currently, only two vaccines against P. falciparum are recommended by the World Health Organization: RTS,S/AS01 and, more recently, R21/Matrix-M. Multiple studies involving different vaccines (RTS,S, PfRAS, PvRAS) have evaluated the transcriptome of whole blood and peripheral blood mononuclear cells (PBMCs). These data are available in public repositories such as the NCBI Gene Expression Omnibus (GEO) and can be repurposed for new analyses. Objectives. Our primary goal is to identify a set of genes associated with the immune response induced by vaccination, using multiple cohorts and different vaccines. We aim to identify both a unified signature and a signature specific to the RTS,S vaccine, then compare the two to analyze similarities and differences. Methodology. We identified 14 datasets in public repositories, totaling 2,054 samples and over 3 TB of data volume. We conducted three metaanalyses: one using pre-vaccination samples, another combining pre- and post-vaccination samples, and a third focusing exclusively on cohorts that used the RTS,S vaccine. Our results were generated using tools such as MetaIntegrator, an R programming language package, to identify differential gene expression across groups. Results. We found that prevaccination gene expression could not predict vaccine efficacy, as differences in expression between protected and nonprotected individuals prior to vaccination were minimal. Subsequent analyses suggest that a pre-vaccination transcriptional profile associated with lymphocytes correlates with protection. In the second meta-analysis, comparing pre- and post-vaccination samples, we identified a unified transcriptional signature of malaria vaccination. The results demonstrate robust activation of myeloid cell-mediated inflammatory responses and interferons, alongside increased expression of genes related to antigen presentation and blood coagulation. In our final meta-analysis, using only RTS,S vaccine cohorts with different adjuvants, we identified a vaccine-specific signature. Conclusion. We identified a signature specific to the RTS,S vaccine and observed that while there is overlap between its gene components and the unified signature of all vaccines, significant differences remain, which are only captured when other vaccines are included in the meta-analysis. We conclude that transcriptomic meta-analyses hold translational potential to enhance vaccine monitoring and efficacy.