Antigen-stimulated PBMC transcriptional protective signatures for malaria immunization

Moncunill, Gemma and Scholzen, Anja and Mpina, Maximillian and Nhabomba, Augusto and Hounkpatin, Aurore Bouyoukou and Osaba, Lourdes and Valls, Raquel and Campo, Joseph J. and Sanz, Hèctor and Jairoce, Chenjerai and Williams, Nana Aba and Pasini, Erica M. and Arteta, David and Maynou, Joan and Palacios, Lourdes and Duran-Frigola, Miquel and Aponte, John J. and Kocken, Clemens H. M. and Agnandji, Selidji Todagbe and Mas, José Manuel and Mordmüller, Benjamin and Daubenberger, Claudia and Sauerwein, Robert and Dobaño, Carlota. (2020) Antigen-stimulated PBMC transcriptional protective signatures for malaria immunization. Science Translational Medicine, 12 (543). eaay8924.

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Official URL: https://edoc.unibas.ch/76873/

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Identifying immune correlates of protection and mechanisms of immunity accelerates and streamlines the development of vaccines. RTS,S/AS01E, the most clinically 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 identifying correlates of vaccine-induced immunity based on transcriptomes of peripheral blood mononuclear cells from individuals immunized with RTS,S/AS01E or chemoattenuated sporozoites stimulated with parasite antigens in vitro. Specifically, we used samples of individuals from two age cohorts and three African countries participating in an RTS,S/AS01E pediatric phase 3 trial and malaria-naïve individuals participating in a CPS trial. We identified both preimmunization and postimmunization transcriptomic signatures correlating with protection. Signatures were validated in independent children and infants from the RTS,S/AS01E phase 3 trial and individuals from an independent CPS trial with high accuracies (>70%). Transcription modules revealed interferon, NF-κB, Toll-like receptor (TLR), and monocyte-related signatures associated with protection. Preimmunization signatures suggest that priming the immune system before vaccination could potentially improve vaccine immunogenicity and efficacy. Last, 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.
Faculties and Departments:09 Associated Institutions > Swiss Tropical and Public Health Institute (Swiss TPH)
09 Associated Institutions > Swiss Tropical and Public Health Institute (Swiss TPH) > Department of Medical Parasitology and Infection Biology (MPI) > Clinical Immunology (Daubenberger)
UniBasel Contributors:Mpina, Maximillian and Daubenberger, Claudia
Item Type:Article, refereed
Article Subtype:Research Article
Publisher:American Association for the Advancement of Science
Note:Publication type according to Uni Basel Research Database: Journal article
Identification Number:
Last Modified:17 Jun 2020 10:11
Deposited On:17 Jun 2020 10:11

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