Distinct immune responses associated with vaccination status and protection outcomes after malaria challenge.
Understanding immune mechanisms that mediate malaria protection is critical for improving vaccine development. Vaccination with radiation-attenuated Plasmodium falciparum sporozoites (PfRAS) induces high level of sterilizing immunity against malaria and serves as a valuable tool for the study of pro...
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| Format: | Article |
| Language: | English |
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Public Library of Science (PLoS)
2023-05-01
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| Series: | PLoS Pathogens |
| Online Access: | https://journals.plos.org/plospathogens/article/file?id=10.1371/journal.ppat.1011051&type=printable |
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| author | Damian A Oyong Fergal J Duffy Maxwell L Neal Ying Du Jason Carnes Katharine V Schwedhelm Nina Hertoghs Seong-Hwan Jun Helen Miller John D Aitchison Stephen C De Rosa Evan W Newell M Juliana McElrath Suzanne M McDermott Kenneth D Stuart |
| author_facet | Damian A Oyong Fergal J Duffy Maxwell L Neal Ying Du Jason Carnes Katharine V Schwedhelm Nina Hertoghs Seong-Hwan Jun Helen Miller John D Aitchison Stephen C De Rosa Evan W Newell M Juliana McElrath Suzanne M McDermott Kenneth D Stuart |
| author_sort | Damian A Oyong |
| collection | DOAJ |
| description | Understanding immune mechanisms that mediate malaria protection is critical for improving vaccine development. Vaccination with radiation-attenuated Plasmodium falciparum sporozoites (PfRAS) induces high level of sterilizing immunity against malaria and serves as a valuable tool for the study of protective mechanisms. To identify vaccine-induced and protection-associated responses during malarial infection, we performed transcriptome profiling of whole blood and in-depth cellular profiling of PBMCs from volunteers who received either PfRAS or noninfectious mosquito bites, followed by controlled human malaria infection (CHMI) challenge. In-depth single-cell profiling of cell subsets that respond to CHMI in mock-vaccinated individuals showed a predominantly inflammatory transcriptome response. Whole blood transcriptome analysis revealed that gene sets associated with type I and II interferon and NK cell responses were increased in prior to CHMI while T and B cell signatures were decreased as early as one day following CHMI in protected vaccinees. In contrast, non-protected vaccinees and mock-vaccinated individuals exhibited shared transcriptome changes after CHMI characterized by decreased innate cell signatures and inflammatory responses. Additionally, immunophenotyping data showed different induction profiles of vδ2+ γδ T cells, CD56+ CD8+ T effector memory (Tem) cells, and non-classical monocytes between protected vaccinees and individuals developing blood-stage parasitemia, following treatment and resolution of infection. Our data provide key insights in understanding immune mechanistic pathways of PfRAS-induced protection and infective CHMI. We demonstrate that vaccine-induced immune response is heterogenous between protected and non-protected vaccinees and that inducted-malaria protection by PfRAS is associated with early and rapid changes in interferon, NK cell and adaptive immune responses. Trial Registration: ClinicalTrials.gov NCT01994525. |
| format | Article |
| id | doaj-art-5e95f5d58ff341c091cc9cbb0bcf49d6 |
| institution | Kabale University |
| issn | 1553-7366 1553-7374 |
| language | English |
| publishDate | 2023-05-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS Pathogens |
| spelling | doaj-art-5e95f5d58ff341c091cc9cbb0bcf49d62025-08-20T03:28:13ZengPublic Library of Science (PLoS)PLoS Pathogens1553-73661553-73742023-05-01195e101105110.1371/journal.ppat.1011051Distinct immune responses associated with vaccination status and protection outcomes after malaria challenge.Damian A OyongFergal J DuffyMaxwell L NealYing DuJason CarnesKatharine V SchwedhelmNina HertoghsSeong-Hwan JunHelen MillerJohn D AitchisonStephen C De RosaEvan W NewellM Juliana McElrathSuzanne M McDermottKenneth D StuartUnderstanding immune mechanisms that mediate malaria protection is critical for improving vaccine development. Vaccination with radiation-attenuated Plasmodium falciparum sporozoites (PfRAS) induces high level of sterilizing immunity against malaria and serves as a valuable tool for the study of protective mechanisms. To identify vaccine-induced and protection-associated responses during malarial infection, we performed transcriptome profiling of whole blood and in-depth cellular profiling of PBMCs from volunteers who received either PfRAS or noninfectious mosquito bites, followed by controlled human malaria infection (CHMI) challenge. In-depth single-cell profiling of cell subsets that respond to CHMI in mock-vaccinated individuals showed a predominantly inflammatory transcriptome response. Whole blood transcriptome analysis revealed that gene sets associated with type I and II interferon and NK cell responses were increased in prior to CHMI while T and B cell signatures were decreased as early as one day following CHMI in protected vaccinees. In contrast, non-protected vaccinees and mock-vaccinated individuals exhibited shared transcriptome changes after CHMI characterized by decreased innate cell signatures and inflammatory responses. Additionally, immunophenotyping data showed different induction profiles of vδ2+ γδ T cells, CD56+ CD8+ T effector memory (Tem) cells, and non-classical monocytes between protected vaccinees and individuals developing blood-stage parasitemia, following treatment and resolution of infection. Our data provide key insights in understanding immune mechanistic pathways of PfRAS-induced protection and infective CHMI. We demonstrate that vaccine-induced immune response is heterogenous between protected and non-protected vaccinees and that inducted-malaria protection by PfRAS is associated with early and rapid changes in interferon, NK cell and adaptive immune responses. Trial Registration: ClinicalTrials.gov NCT01994525.https://journals.plos.org/plospathogens/article/file?id=10.1371/journal.ppat.1011051&type=printable |
| spellingShingle | Damian A Oyong Fergal J Duffy Maxwell L Neal Ying Du Jason Carnes Katharine V Schwedhelm Nina Hertoghs Seong-Hwan Jun Helen Miller John D Aitchison Stephen C De Rosa Evan W Newell M Juliana McElrath Suzanne M McDermott Kenneth D Stuart Distinct immune responses associated with vaccination status and protection outcomes after malaria challenge. PLoS Pathogens |
| title | Distinct immune responses associated with vaccination status and protection outcomes after malaria challenge. |
| title_full | Distinct immune responses associated with vaccination status and protection outcomes after malaria challenge. |
| title_fullStr | Distinct immune responses associated with vaccination status and protection outcomes after malaria challenge. |
| title_full_unstemmed | Distinct immune responses associated with vaccination status and protection outcomes after malaria challenge. |
| title_short | Distinct immune responses associated with vaccination status and protection outcomes after malaria challenge. |
| title_sort | distinct immune responses associated with vaccination status and protection outcomes after malaria challenge |
| url | https://journals.plos.org/plospathogens/article/file?id=10.1371/journal.ppat.1011051&type=printable |
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