Antigen-stimulated PBMC transcriptional signatures of protection upon malaria sporozoite and RTS,S/AS01E immunizations
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA605110 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description: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.
2020-05-13 | GSE144826 | GEO
Project description:We applied a systems biology approach to study immune responses in subjects receiving 3 consecutive immunizations with RTS,S/AS01 (RRR), or in those receiving 2 immunizations of RTS,S/AS01, following a primary immunization with adenoviral Ad35 (ARR) vector expressing circumsporozoite protein.
2017-03-01 | GSE89292 | GEO
Project description:RTS,S is the sole candidate vaccine shown to provide protection against infection to malaria-naive adults challenged with mosquito-borne homologous falciparum malaria and protection against infection and clinical and severe disease to volunteers in malaria-endemic Africa who were exposed to diverse Plasmodium falciparum strains. In this experiment we profiled gene expression in PBMCs after vaccination with the RTS,S candidate malaria vaccine in a controlled human malaria infection study. Subjects were vaccinated with three doses of the RTS,S candidate malaria vaccine. Blood samples for PBMC isolation and subsequent gene expression analysis were taken on day 0 (0m), day of the third vaccination (8w), 1 day post third vaccination (8w1d), 3 days post third vaccination (8w3d), the day of the infection (10w), 1 day post infection (10w1d), and 5 days post infection (10w5d). After infection the subjects were closely monitored for parasitemia. The response to the controlled infection was recorded as follows: no parasitemia (P, protected), parasitemia in the same time frame as the control group (NP, not protected), parasitemia later than the control group (DL, delayed). In addition to the experimental factors, a confounding factor was identified in the data analysis related to the use of a specific kit batch (Kit A or B).
2017-04-27 | E-MTAB-4629 | biostudies-arrayexpress
Project description:Identification of gene signatures that are associated with protection in RTS,S malaria vaccination study
2020-04-21 | GSE102288 | GEO
Project description:Route of immunization can markedly influence the quality of immune response. Here, we show that intradermal (ID) but not intramuscular (IM) modified vaccinia Ankara (MVA) vaccinations provide protection from acquisition of intravaginal tier2 SHIV challenges in female macaques. Both routes of vaccination induced comparable levels of serum IgG with neutralizing and non-neutralizing activities. The protection in MVA-ID group correlated positively with serum neutralizing and antibody-dependent phagocytic activities, and envelope-specific vaginal IgA; while the limited protection in MVA-IM group correlated only with serum neutralizing activity. MVA-ID immunizations induced greater germinal center Tfh and B cell responses, reduced the ratio of Th1 to Tfh cells in blood and showed lower activation of intermediate monocytes and inflammasome compared to MVA-IM immunizations. This lower innate activation correlated negatively with induction of Tfh responses. These data demonstrate that the MVA-ID vaccinations protect against intravaginal SHIV challenges by modulating the innate and T helper responses.
2023-07-27 | GSE219118 | GEO
Project description:Genome-wide investigation of transcriptional regulation in malaria sporozoite
| PRJNA877191 | ENA
Project description:MalariaM-bM-^@M-^Ys cycle of infection requires parasite transmission between a mosquito vector and a vertebrate host. Plasmodium regulates transmission by translationally repressing specific mRNAs until their products are needed. We demonstrate that the Plasmodium yoelii Pumilio-FBF family member Puf2 allows the sporozoite to retain its infectivity in the mosquito salivary glands while awaiting transmission. Puf2 mediates this critical feature solely through its RNA-Binding Domain (RBD) likely by protecting and silencing specific mRNAs. Puf2 storage granules are distinct from stress granules and P-bodies and dissolve rapidly after infection of hepatocytes, likely releasing the protected and silenced transcripts for M-bM-^@M-^Xjust-in-timeM-bM-^@M-^Y translation by early exoerythrocytic forms (EEFs). Further corroborating this model, pypuf2- sporozoites have no apparent defect in host infection early after invading the salivary glands, but become progressively noninfectious and subsequently prematurely transform into EEFs during prolonged salivary gland residence. In contrast, the premature overexpression of Puf2 in oocysts causes striking deregulation of sporozoite maturation, resulting in fewer oocyst sporozoites that are non-infectious and unable to colonize the salivary glands. Maintenance of Puf2 expression in liver stage parasites produces no phenotype, suggesting that a window of permissive expression exists. Finally, by conducting the first comparative RNAseq analysis of Plasmodium sporozoites, we have uncovered that Puf2 may play a role in both the protection of specific transcripts as well as RNA turnover via the CCR4/Not complex. These findings uncover requirements for maintaining a window of opportunity for the malaria parasite to accommodate the unpredictable moment of transmission from mosquito to vertebrate host. Wild-type (Py17XNL) and pypuf2 -salivary gland sporozoites
2012-10-27 | E-GEOD-41873 | biostudies-arrayexpress
Project description:Identification of gene signatures that are associated with RTS,S-mediated protection against controlled malaria infection
2020-04-21 | GSE103401 | GEO
Project description:Malaria’s cycle of infection requires parasite transmission between a mosquito vector and a vertebrate host. Plasmodium regulates transmission by translationally repressing specific mRNAs until their products are needed. We demonstrate that the Plasmodium yoelii Pumilio-FBF family member Puf2 allows the sporozoite to retain its infectivity in the mosquito salivary glands while awaiting transmission. Puf2 mediates this critical feature solely through its RNA-Binding Domain (RBD) likely by protecting and silencing specific mRNAs. Puf2 storage granules are distinct from stress granules and P-bodies and dissolve rapidly after infection of hepatocytes, likely releasing the protected and silenced transcripts for ‘just-in-time’ translation by early exoerythrocytic forms (EEFs). Further corroborating this model, pypuf2- sporozoites have no apparent defect in host infection early after invading the salivary glands, but become progressively noninfectious and subsequently prematurely transform into EEFs during prolonged salivary gland residence. In contrast, the premature overexpression of Puf2 in oocysts causes striking deregulation of sporozoite maturation, resulting in fewer oocyst sporozoites that are non-infectious and unable to colonize the salivary glands. Maintenance of Puf2 expression in liver stage parasites produces no phenotype, suggesting that a window of permissive expression exists. Finally, by conducting the first comparative RNAseq analysis of Plasmodium sporozoites, we have uncovered that Puf2 may play a role in both the protection of specific transcripts as well as RNA turnover via the CCR4/Not complex. These findings uncover requirements for maintaining a window of opportunity for the malaria parasite to accommodate the unpredictable moment of transmission from mosquito to vertebrate host.
2012-10-27 | GSE41873 | GEO
Project description:Sporozoite is the stage in which malaria parasites initially infect the vertebrate host. Elucidation of gene regulation in this stage will promote the investigation of mechanisms of liver infection by this parasite and contribute to development of strategies for preventing the malaria transmission. AP2-Sp is a transcription factor essential for formation of sporozoites or sporogony, which take place in oocysts on the midgut of infected mosquitoes. To understand the role of this transcription factor in the transcriptional regulatory system of this stage we performed ChIP-seq analysis using whole mosquito midguts containing late oocysts as start materials and explore its target genes genome-widely. Target genes were composed of 640 genes, which encompassed various functional categories and were contained genes involved in distinct processes parasites pass through in this stage, from sporogony to development into the liver stage. Furthermore, RNA-seq analysis showed that these genes constituted majority of the genes highly expressed in in this stage. These results suggested that this TF determines basal pattern of gene expression of this stage by targeting a broad range of genes directly.
2022-11-05 | GSE212753 | GEO