Identifying immune correlates of protection and mechanisms of immunity accelerates and streamlines the development of vaccines. RTS,S/AS01E, the most advanced malaria vaccine, has moderate efficacy in African children. In contrast, immunization with sporozoites under antimalarial chemoprophylaxis (CPS immunization) can provide 100% sterile protection in naïve adults. We used systems biology approaches to identify correlates of vaccine-induced immunity based on transcriptomes of peripheral blood mononuclear cells from subjects immunized with RTS,S/AS01E or chemo-attenuated sporozoites stimulated with parasite antigens in vitro. Specifically, we used samples of subjects from two age cohorts and 3 African countries participating in an RTS,S/AS01E pediatric phase 3 trial and malaria-naïve subjects participating in a CPS trial. We identified both pre-immunization and post-immunization transcriptomic signatures correlating with protection. Signatures were validated in independent children and infants from the RTS,S/AS01E phase 3 trial and subjects from an independent CPS trial with high accuracies (>70%). Transcription modules revealed interferon, NF-B, TLR, and monocyte-related signatures associated with protection. Pre-immunization signatures suggest the potential for strategies to prime the immune system before vaccination towards improving vaccine immunogenicity and efficacy. Finally, signatures of protection could be useful to determine efficacy in clinical trials, accelerating vaccine candidate testing. Nevertheless, signatures should be tested more extensively across multiple cohorts and trials to demonstrate their universal predictive capacity.
Antigen-stimulated PBMC transcriptional protective signatures for malaria immunization.
Sex, Specimen part, Subject, Time
View SamplesWe sequenced mRNA from mouse EML cell line under Kai1 knockdown or Kai1 overexpressing condition. KAI1 belongs to tetraspanin superfamily and is known as suppressor of tumor metastasis. Overall design: Examination of mRNA levels in wildtype (WT) and KAI1 knockdown EML cells were generated by deep sequencing, in duplicate, using Illumina GAIIx. Examination of mRNA levels in wildtype (WT) and KAI1 overexpressing EML cells were also generated in single set.
CD82/KAI1 Maintains the Dormancy of Long-Term Hematopoietic Stem Cells through Interaction with DARC-Expressing Macrophages.
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View SamplesWe apply RNA-seq to limited populations of Innate Lymphoid Cells type 2 and type 3 (ILC2s and ILC3s, respectively) in human individuals infected with acute HIV in the FRESH study. We measured the whole transcriptome of ILC2s and ILC3s in both untreated (n=2) and ART treated (n=2) individuals over the course of infection, in order to compare these populations at key points during infection, namely: viral detection, peak viremia, and weeks past peak viremia (6-7 weeks post detection). Lacking true biological replicates, HIV- patients in the same study (n=9) were used as replicates to conduct Differential Expression (DE) analysis between time points in both ILC2s and ILC3s on a patient by patient basis. In untreated patients, ILC2s and ILC3s differentially expressed genes associated with apoptosis and cell death between peak viremia and viral detection, while ART treated patients' ILC2s and ILC3s demonstrated a mitigated response. Comparing 6-7 weeks after detection with peak viremia revealed a relative decrease in genes associated in cell death in untreated patients, while ART treated patients showed varied responses where several DE genes were associated with immune response. Overall design: RNA-seq of two Innate Lymphoid Cell populations in 2 HIV+ untreated patients, 2 HIV+ ART treated patients, and 9 HIV- patients (control, replicates).
Innate Lymphoid Cells Are Depleted Irreversibly during Acute HIV-1 Infection in the Absence of Viral Suppression.
No sample metadata fields
View SamplesWe report the phenotype of human lung ILC2 and ILC3 populations from individuals with tuberculosis (TB) and non-TB cancer controls. We find that ILC2s demonstrate moderate transcriptional differences in TB infection, whereas ILC3s demonstrate large differences. Overall design: ILC2s and ILC3s were purified by FACS from lung biopsies from TB infected lung tissue and peripheral healthy lung tissue from individuals with cancer. Low-input RNA-seq was performed on 1-3 replicates (dependent on cell number) on 5 individuals with TB infection and 2 controls.
Group 3 innate lymphoid cells mediate early protective immunity against tuberculosis.
Specimen part, Disease, Subject
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