Antigen-stimulated PBMC transcriptional protective signatures for malaria immunization.

Autor:	Moncunill G; ISGlobal, Hospital Clínic-Universitat de Barcelona, E-08036 Barcelona, Catalonia, Spain. gemma.moncunill@isglobal.org carlota.dobano@isglobal.org.; Centro de Investigação em Saúde de Manhiça (CISM), Rua 12, Cambeve, Vila de Manhiça, CP 1929 Maputo, Mozambique., Scholzen A; Department of Medical Microbiology, Radboud University Medical Center, 6500 HB Nijmegen, Netherlands., Mpina M; Ifakara Health Institute, Bagamoyo Research and Training Centre. P.O. Box 74, Bagamoyo, Tanzania.; Swiss Tropical and Public Health Institute, Socinstrasse 57, 4002 Basel, Switzerland.; University of Basel, Petersplatz 1, 4001 Basel, Switzerland., Nhabomba A; Centro de Investigação em Saúde de Manhiça (CISM), Rua 12, Cambeve, Vila de Manhiça, CP 1929 Maputo, Mozambique., Hounkpatin AB; Centre de Recherches Médicales de Lambaréné (CERMEL), BP 242 Lambaréné, Gabon.; Institute of Tropical Medicine and German Center for Infection Research, University of Tübingen, Wilhelmstraße 27, D-72074 Tübingen, Germany., Osaba L; Progenika Biopharma. A Grifols Company, S.A., 48160 Derio, Vizcaya, Spain., Valls R; Anaxomics Biotech, S.L, 08008 Barcelona, Spain., Campo JJ; ISGlobal, Hospital Clínic-Universitat de Barcelona, E-08036 Barcelona, Catalonia, Spain.; Centro de Investigação em Saúde de Manhiça (CISM), Rua 12, Cambeve, Vila de Manhiça, CP 1929 Maputo, Mozambique., Sanz H; ISGlobal, Hospital Clínic-Universitat de Barcelona, E-08036 Barcelona, Catalonia, Spain., Jairoce C; Centro de Investigação em Saúde de Manhiça (CISM), Rua 12, Cambeve, Vila de Manhiça, CP 1929 Maputo, Mozambique., Williams NA; ISGlobal, Hospital Clínic-Universitat de Barcelona, E-08036 Barcelona, Catalonia, Spain., Pasini EM; Department of Parasitology, Biomedical Primate Research Centre, Rijswijk, Netherlands., Arteta D; Progenika Biopharma. A Grifols Company, S.A., 48160 Derio, Vizcaya, Spain., Maynou J; Progenika Biopharma. A Grifols Company, S.A., 48160 Derio, Vizcaya, Spain., Palacios L; Progenika Biopharma. A Grifols Company, S.A., 48160 Derio, Vizcaya, Spain., Duran-Frigola M; Institute for Research in Biomedicine (IRB Barcelona). The Barcelona Institute of Science and Technology, 08028 Barcelona, Catalonia, Spain., Aponte JJ; ISGlobal, Hospital Clínic-Universitat de Barcelona, E-08036 Barcelona, Catalonia, Spain., Kocken CHM; Department of Parasitology, Biomedical Primate Research Centre, Rijswijk, Netherlands., Agnandji ST; Centre de Recherches Médicales de Lambaréné (CERMEL), BP 242 Lambaréné, Gabon.; Institute of Tropical Medicine and German Center for Infection Research, University of Tübingen, Wilhelmstraße 27, D-72074 Tübingen, Germany., Mas JM; Anaxomics Biotech, S.L, 08008 Barcelona, Spain., Mordmüller B; Institute of Tropical Medicine and German Center for Infection Research, University of Tübingen, Wilhelmstraße 27, D-72074 Tübingen, Germany., Daubenberger C; Swiss Tropical and Public Health Institute, Socinstrasse 57, 4002 Basel, Switzerland.; University of Basel, Petersplatz 1, 4001 Basel, Switzerland., Sauerwein R; Department of Medical Microbiology, Radboud University Medical Center, 6500 HB Nijmegen, Netherlands., Dobaño C; ISGlobal, Hospital Clínic-Universitat de Barcelona, E-08036 Barcelona, Catalonia, Spain. gemma.moncunill@isglobal.org carlota.dobano@isglobal.org.; Centro de Investigação em Saúde de Manhiça (CISM), Rua 12, Cambeve, Vila de Manhiça, CP 1929 Maputo, Mozambique.
Jazyk:	angličtina
Zdroj:	Science translational medicine [Sci Transl Med] 2020 May 13; Vol. 12 (543).
DOI:	10.1126/scitranslmed.aay8924
Abstrakt:	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. (Copyright © 2020 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works.)
Databáze:	MEDLINE
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