Human transcriptional signature of protection after Plasmodium falciparum immunization and infectious challenge via mosquito bites
The identification of immune correlates of protection against infectious pathogens will accelerate the design and optimization of recombinant and subunit vaccines. Systematic analyses such as immunoprofiling including serological, cellular, and molecular assessments supported by computational tools...
Saved in:
| Main Authors: | , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Taylor & Francis Group
2023-12-01
|
| Series: | Human Vaccines & Immunotherapeutics |
| Subjects: | |
| Online Access: | https://www.tandfonline.com/doi/10.1080/21645515.2023.2282693 |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1850133578344562688 |
|---|---|
| author | Marie Mura Burook Misganaw Aarti Gautam Tanisha Robinson Sidhartha Chaudhury Neha Bansal Andrew J. Martins John Tsang Rasha Hammamieh Elke Bergmann-Leitner |
| author_facet | Marie Mura Burook Misganaw Aarti Gautam Tanisha Robinson Sidhartha Chaudhury Neha Bansal Andrew J. Martins John Tsang Rasha Hammamieh Elke Bergmann-Leitner |
| author_sort | Marie Mura |
| collection | DOAJ |
| description | The identification of immune correlates of protection against infectious pathogens will accelerate the design and optimization of recombinant and subunit vaccines. Systematic analyses such as immunoprofiling including serological, cellular, and molecular assessments supported by computational tools are key to not only identify correlates of protection but also biomarkers of disease susceptibility. The current study expands our previous cellular and serological profiling of vaccine-induced responses to a whole parasite malaria vaccine. The irradiated sporozoite model was chosen as it is considered the most effective vaccine against malaria. In contrast to whole blood transcriptomics analysis, we stimulated peripheral blood mononuclear cells (PBMC) with sporozoites and enriched for antigen-specific cells prior to conducting transcriptomics analysis. By focusing on transcriptional events triggered by antigen-specific stimulation, we were able to uncover quantitative and qualitative differences between protected and non-protected individuals to controlled human malaria infections and identified differentially expressed genes associated with sporozoite-specific responses. Further analyses including pathway and gene set enrichment analysis revealed that vaccination with irradiated sporozoites induced a transcriptomic profile associated with Th1-responses, Interferon-signaling, antigen-presentation, and inflammation. Analyzing longitudinal time points not only post-vaccination but also post-controlled human malaria infection further revealed that the transcriptomic profile of protected vs non-protected individuals was not static but continued to diverge over time. The results lay the foundation for comparing protective immune signatures induced by various vaccine platforms to uncover immune correlates of protection that are common across platforms. |
| format | Article |
| id | doaj-art-3dbd74f968ee436faf72c29a5b48eac8 |
| institution | OA Journals |
| issn | 2164-5515 2164-554X |
| language | English |
| publishDate | 2023-12-01 |
| publisher | Taylor & Francis Group |
| record_format | Article |
| series | Human Vaccines & Immunotherapeutics |
| spelling | doaj-art-3dbd74f968ee436faf72c29a5b48eac82025-08-20T02:31:56ZengTaylor & Francis GroupHuman Vaccines & Immunotherapeutics2164-55152164-554X2023-12-0119310.1080/21645515.2023.2282693Human transcriptional signature of protection after Plasmodium falciparum immunization and infectious challenge via mosquito bitesMarie Mura0Burook Misganaw1Aarti Gautam2Tanisha Robinson3Sidhartha Chaudhury4Neha Bansal5Andrew J. Martins6John Tsang7Rasha Hammamieh8Elke Bergmann-Leitner9Immunology Core, Biologics Research & Development, WRAIR-Walter Reed Army Institute of Research, Silver Spring, MD, USAMedical Readiness Systems Biology, Center for Military Psychiatry and Neuroscience, Walter Reed Army Institute of Research, Silver Spring, MD, USAMedical Readiness Systems Biology, Center for Military Psychiatry and Neuroscience, Walter Reed Army Institute of Research, Silver Spring, MD, USAImmunology Core, Biologics Research & Development, WRAIR-Walter Reed Army Institute of Research, Silver Spring, MD, USACenter of Enabling Capabilties, WRAIR-Walter Reed Army Institute of Research, Silver Spring, MD, USAMultiscale Systems Biology Section, Laboratory of Immune System Biology, NIAID, NIH, Bethesda, MD, USAMultiscale Systems Biology Section, Laboratory of Immune System Biology, NIAID, NIH, Bethesda, MD, USAMultiscale Systems Biology Section, Laboratory of Immune System Biology, NIAID, NIH, Bethesda, MD, USAMedical Readiness Systems Biology, Center for Military Psychiatry and Neuroscience, Walter Reed Army Institute of Research, Silver Spring, MD, USAImmunology Core, Biologics Research & Development, WRAIR-Walter Reed Army Institute of Research, Silver Spring, MD, USAThe identification of immune correlates of protection against infectious pathogens will accelerate the design and optimization of recombinant and subunit vaccines. Systematic analyses such as immunoprofiling including serological, cellular, and molecular assessments supported by computational tools are key to not only identify correlates of protection but also biomarkers of disease susceptibility. The current study expands our previous cellular and serological profiling of vaccine-induced responses to a whole parasite malaria vaccine. The irradiated sporozoite model was chosen as it is considered the most effective vaccine against malaria. In contrast to whole blood transcriptomics analysis, we stimulated peripheral blood mononuclear cells (PBMC) with sporozoites and enriched for antigen-specific cells prior to conducting transcriptomics analysis. By focusing on transcriptional events triggered by antigen-specific stimulation, we were able to uncover quantitative and qualitative differences between protected and non-protected individuals to controlled human malaria infections and identified differentially expressed genes associated with sporozoite-specific responses. Further analyses including pathway and gene set enrichment analysis revealed that vaccination with irradiated sporozoites induced a transcriptomic profile associated with Th1-responses, Interferon-signaling, antigen-presentation, and inflammation. Analyzing longitudinal time points not only post-vaccination but also post-controlled human malaria infection further revealed that the transcriptomic profile of protected vs non-protected individuals was not static but continued to diverge over time. The results lay the foundation for comparing protective immune signatures induced by various vaccine platforms to uncover immune correlates of protection that are common across platforms.https://www.tandfonline.com/doi/10.1080/21645515.2023.2282693Malariavaccinehuman controlled malaria infectionprotectiontranscriptomic |
| spellingShingle | Marie Mura Burook Misganaw Aarti Gautam Tanisha Robinson Sidhartha Chaudhury Neha Bansal Andrew J. Martins John Tsang Rasha Hammamieh Elke Bergmann-Leitner Human transcriptional signature of protection after Plasmodium falciparum immunization and infectious challenge via mosquito bites Human Vaccines & Immunotherapeutics Malaria vaccine human controlled malaria infection protection transcriptomic |
| title | Human transcriptional signature of protection after Plasmodium falciparum immunization and infectious challenge via mosquito bites |
| title_full | Human transcriptional signature of protection after Plasmodium falciparum immunization and infectious challenge via mosquito bites |
| title_fullStr | Human transcriptional signature of protection after Plasmodium falciparum immunization and infectious challenge via mosquito bites |
| title_full_unstemmed | Human transcriptional signature of protection after Plasmodium falciparum immunization and infectious challenge via mosquito bites |
| title_short | Human transcriptional signature of protection after Plasmodium falciparum immunization and infectious challenge via mosquito bites |
| title_sort | human transcriptional signature of protection after plasmodium falciparum immunization and infectious challenge via mosquito bites |
| topic | Malaria vaccine human controlled malaria infection protection transcriptomic |
| url | https://www.tandfonline.com/doi/10.1080/21645515.2023.2282693 |
| work_keys_str_mv | AT mariemura humantranscriptionalsignatureofprotectionafterplasmodiumfalciparumimmunizationandinfectiouschallengeviamosquitobites AT burookmisganaw humantranscriptionalsignatureofprotectionafterplasmodiumfalciparumimmunizationandinfectiouschallengeviamosquitobites AT aartigautam humantranscriptionalsignatureofprotectionafterplasmodiumfalciparumimmunizationandinfectiouschallengeviamosquitobites AT tanisharobinson humantranscriptionalsignatureofprotectionafterplasmodiumfalciparumimmunizationandinfectiouschallengeviamosquitobites AT sidharthachaudhury humantranscriptionalsignatureofprotectionafterplasmodiumfalciparumimmunizationandinfectiouschallengeviamosquitobites AT nehabansal humantranscriptionalsignatureofprotectionafterplasmodiumfalciparumimmunizationandinfectiouschallengeviamosquitobites AT andrewjmartins humantranscriptionalsignatureofprotectionafterplasmodiumfalciparumimmunizationandinfectiouschallengeviamosquitobites AT johntsang humantranscriptionalsignatureofprotectionafterplasmodiumfalciparumimmunizationandinfectiouschallengeviamosquitobites AT rashahammamieh humantranscriptionalsignatureofprotectionafterplasmodiumfalciparumimmunizationandinfectiouschallengeviamosquitobites AT elkebergmannleitner humantranscriptionalsignatureofprotectionafterplasmodiumfalciparumimmunizationandinfectiouschallengeviamosquitobites |