Profiling the antibody response of humans protected by immunization with Plasmodium vivax radiation-attenuated sporozoites

Abstract Malaria sterile immunity has been reproducibly induced by immunization with Plasmodium radiation-attenuated sporozoites (RAS). Analyses of sera from RAS-immunized individuals allowed the identification of P. falciparum antigens, such as the circumsporozoite protein (CSP), the basis for the...

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Main Authors: Mary Lopez-Perez, Aarti Jain, D. Huw Davies, Juan M. Vásquez-Jiménez, Sonia M. Herrera, José Oñate, Philip L. Felgner, Sócrates Herrera, Myriam Arévalo-Herrera
Format: Article
Language:English
Published: Nature Portfolio 2024-02-01
Series:Scientific Reports
Online Access:https://doi.org/10.1038/s41598-024-53175-0
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author Mary Lopez-Perez
Aarti Jain
D. Huw Davies
Juan M. Vásquez-Jiménez
Sonia M. Herrera
José Oñate
Philip L. Felgner
Sócrates Herrera
Myriam Arévalo-Herrera
author_facet Mary Lopez-Perez
Aarti Jain
D. Huw Davies
Juan M. Vásquez-Jiménez
Sonia M. Herrera
José Oñate
Philip L. Felgner
Sócrates Herrera
Myriam Arévalo-Herrera
author_sort Mary Lopez-Perez
collection DOAJ
description Abstract Malaria sterile immunity has been reproducibly induced by immunization with Plasmodium radiation-attenuated sporozoites (RAS). Analyses of sera from RAS-immunized individuals allowed the identification of P. falciparum antigens, such as the circumsporozoite protein (CSP), the basis for the RTS, S and R21Matrix-M vaccines. Similar advances in P. vivax (Pv) vaccination have been elusive. We previously reported 42% (5/12) of sterile protection in malaria-unexposed, Duffy-positive (Fy +) volunteers immunized with PvRAS followed by a controlled human malaria infection (CHMI). Using a custom protein microarray displaying 515 Pv antigens, we found a significantly higher reactivity to PvCSP and one hypothetical protein (PVX_089630) in volunteers protected against P. vivax infection. In mock-vaccinated Fy + volunteers, a strong antibody response to CHMI was also observed. Although the Fy- volunteers immunized with non-irradiated Pv-infected mosquitoes (live sporozoites) did not develop malaria after CHMI, they recognized a high number of antigens, indicating the temporary presence of asexual parasites in peripheral blood. Together, our findings contribute to the understanding of the antibody response to P. vivax infection and allow the identification of novel parasite antigens as vaccine candidates. Trial registration: ClinicalTrials.gov number: NCT 01082341.
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spelling doaj.art-8f73505508e7404eae3cdc664a68ee122024-03-05T18:40:22ZengNature PortfolioScientific Reports2045-23222024-02-0114111210.1038/s41598-024-53175-0Profiling the antibody response of humans protected by immunization with Plasmodium vivax radiation-attenuated sporozoitesMary Lopez-Perez0Aarti Jain1D. Huw Davies2Juan M. Vásquez-Jiménez3Sonia M. Herrera4José Oñate5Philip L. Felgner6Sócrates Herrera7Myriam Arévalo-Herrera8Malaria Vaccine and Drug Development Center (MVDC)Department Physiology & Biophysics, Vaccine R&D Center, University of California IrvineDepartment Physiology & Biophysics, Vaccine R&D Center, University of California IrvineMalaria Vaccine and Drug Development Center (MVDC)Caucaseco Scientific Research CenterImbanaco - QuironSaludDepartment Physiology & Biophysics, Vaccine R&D Center, University of California IrvineMalaria Vaccine and Drug Development Center (MVDC)Malaria Vaccine and Drug Development Center (MVDC)Abstract Malaria sterile immunity has been reproducibly induced by immunization with Plasmodium radiation-attenuated sporozoites (RAS). Analyses of sera from RAS-immunized individuals allowed the identification of P. falciparum antigens, such as the circumsporozoite protein (CSP), the basis for the RTS, S and R21Matrix-M vaccines. Similar advances in P. vivax (Pv) vaccination have been elusive. We previously reported 42% (5/12) of sterile protection in malaria-unexposed, Duffy-positive (Fy +) volunteers immunized with PvRAS followed by a controlled human malaria infection (CHMI). Using a custom protein microarray displaying 515 Pv antigens, we found a significantly higher reactivity to PvCSP and one hypothetical protein (PVX_089630) in volunteers protected against P. vivax infection. In mock-vaccinated Fy + volunteers, a strong antibody response to CHMI was also observed. Although the Fy- volunteers immunized with non-irradiated Pv-infected mosquitoes (live sporozoites) did not develop malaria after CHMI, they recognized a high number of antigens, indicating the temporary presence of asexual parasites in peripheral blood. Together, our findings contribute to the understanding of the antibody response to P. vivax infection and allow the identification of novel parasite antigens as vaccine candidates. Trial registration: ClinicalTrials.gov number: NCT 01082341.https://doi.org/10.1038/s41598-024-53175-0
spellingShingle Mary Lopez-Perez
Aarti Jain
D. Huw Davies
Juan M. Vásquez-Jiménez
Sonia M. Herrera
José Oñate
Philip L. Felgner
Sócrates Herrera
Myriam Arévalo-Herrera
Profiling the antibody response of humans protected by immunization with Plasmodium vivax radiation-attenuated sporozoites
Scientific Reports
title Profiling the antibody response of humans protected by immunization with Plasmodium vivax radiation-attenuated sporozoites
title_full Profiling the antibody response of humans protected by immunization with Plasmodium vivax radiation-attenuated sporozoites
title_fullStr Profiling the antibody response of humans protected by immunization with Plasmodium vivax radiation-attenuated sporozoites
title_full_unstemmed Profiling the antibody response of humans protected by immunization with Plasmodium vivax radiation-attenuated sporozoites
title_short Profiling the antibody response of humans protected by immunization with Plasmodium vivax radiation-attenuated sporozoites
title_sort profiling the antibody response of humans protected by immunization with plasmodium vivax radiation attenuated sporozoites
url https://doi.org/10.1038/s41598-024-53175-0
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