Role of malaria exposure and off-target responses on RTS,S/AS02A vaccine immunogenicity and protection in Mozambican children
Abstract RTS,S/AS01E is the first malaria vaccine implemented for young African children. However, it provides partial protection against Plasmodium falciparum (Pf) malaria, and a better understanding of the mechanisms and determinants of vaccine immunity will help develop second-generation improved...
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Nature Portfolio
2025-06-01
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| Series: | npj Vaccines |
| Online Access: | https://doi.org/10.1038/s41541-025-01167-0 |
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| author | Elisa Fuentes Chenjerai Jairoce Didac Macià Leonie Mayer Jorge P. Torres-Yaguana Marta Vidal Rebeca Santano David L. Narum David Cavanagh Benoit Gamain Ross L. Coppel James G. Beeson Sheetij Dutta Jahit Sacarlal Ruth Aguilar Gemma Moncunill Carlota Dobaño |
| author_facet | Elisa Fuentes Chenjerai Jairoce Didac Macià Leonie Mayer Jorge P. Torres-Yaguana Marta Vidal Rebeca Santano David L. Narum David Cavanagh Benoit Gamain Ross L. Coppel James G. Beeson Sheetij Dutta Jahit Sacarlal Ruth Aguilar Gemma Moncunill Carlota Dobaño |
| author_sort | Elisa Fuentes |
| collection | DOAJ |
| description | Abstract RTS,S/AS01E is the first malaria vaccine implemented for young African children. However, it provides partial protection against Plasmodium falciparum (Pf) malaria, and a better understanding of the mechanisms and determinants of vaccine immunity will help develop second-generation improved vaccines. We measured IgG to vaccine target and Pf blood-stage off-target proteins before and after vaccination in 874 children aged 1–4 years in a phase 2b trial of RTS,S/AS02A in Mozambique. We found that naturally acquired PfCSP IgG levels pre-vaccination were positively associated with RTS,S immunogenicity. Increased levels of IgG to the C-terminus and NANP-repeat regions of PfCSP, and to PfMSP5 and PfMSP1 block 2, following vaccination, were significantly associated with a lower hazard of clinical malaria over 6 months. Thus, immune priming, anti-PfCSP C-terminus and off-target antibody responses contributed to malaria protection after adjusting for prior Pf exposure, and this could guide strategies for optimizing the immunogen and vaccine deployment. |
| format | Article |
| id | doaj-art-965e0e45ad1a4e42bca8a27d09b5a56b |
| institution | DOAJ |
| issn | 2059-0105 |
| language | English |
| publishDate | 2025-06-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | npj Vaccines |
| spelling | doaj-art-965e0e45ad1a4e42bca8a27d09b5a56b2025-08-20T03:10:38ZengNature Portfolionpj Vaccines2059-01052025-06-0110111010.1038/s41541-025-01167-0Role of malaria exposure and off-target responses on RTS,S/AS02A vaccine immunogenicity and protection in Mozambican childrenElisa Fuentes0Chenjerai Jairoce1Didac Macià2Leonie Mayer3Jorge P. Torres-Yaguana4Marta Vidal5Rebeca Santano6David L. Narum7David Cavanagh8Benoit Gamain9Ross L. Coppel10James G. Beeson11Sheetij Dutta12Jahit Sacarlal13Ruth Aguilar14Gemma Moncunill15Carlota Dobaño16ISGlobalISGlobalISGlobalISGlobalISGlobalISGlobalISGlobalLaboratory of Malaria Immunology and Vaccinology, National Institute of Allergy and Infectious Diseases, National Institutes of HealthInstitute of Immunology & Infection Research and Centre for Immunity, Infection & Evolution, Ashworth Laboratories, School of Biological Sciences, University of Edinburgh, King’s BuildingsSorbonne Université, CNRS, Inserm, Centre d’Immunologie et des Maladies Infectieuses, CIMIInfection and Immunity Program, Monash Biomedicine Discovery Institute and Department of Microbiology, Monash UniversityMacfarlane Burnet Institute for Medical Research and Public HealthU.S. Military Malaria Vaccine Program, Walter Reed Army Institute of Research (WRAIR)Centro de Investigação em Saúde de ManhiçaISGlobalISGlobalISGlobalAbstract RTS,S/AS01E is the first malaria vaccine implemented for young African children. However, it provides partial protection against Plasmodium falciparum (Pf) malaria, and a better understanding of the mechanisms and determinants of vaccine immunity will help develop second-generation improved vaccines. We measured IgG to vaccine target and Pf blood-stage off-target proteins before and after vaccination in 874 children aged 1–4 years in a phase 2b trial of RTS,S/AS02A in Mozambique. We found that naturally acquired PfCSP IgG levels pre-vaccination were positively associated with RTS,S immunogenicity. Increased levels of IgG to the C-terminus and NANP-repeat regions of PfCSP, and to PfMSP5 and PfMSP1 block 2, following vaccination, were significantly associated with a lower hazard of clinical malaria over 6 months. Thus, immune priming, anti-PfCSP C-terminus and off-target antibody responses contributed to malaria protection after adjusting for prior Pf exposure, and this could guide strategies for optimizing the immunogen and vaccine deployment.https://doi.org/10.1038/s41541-025-01167-0 |
| spellingShingle | Elisa Fuentes Chenjerai Jairoce Didac Macià Leonie Mayer Jorge P. Torres-Yaguana Marta Vidal Rebeca Santano David L. Narum David Cavanagh Benoit Gamain Ross L. Coppel James G. Beeson Sheetij Dutta Jahit Sacarlal Ruth Aguilar Gemma Moncunill Carlota Dobaño Role of malaria exposure and off-target responses on RTS,S/AS02A vaccine immunogenicity and protection in Mozambican children npj Vaccines |
| title | Role of malaria exposure and off-target responses on RTS,S/AS02A vaccine immunogenicity and protection in Mozambican children |
| title_full | Role of malaria exposure and off-target responses on RTS,S/AS02A vaccine immunogenicity and protection in Mozambican children |
| title_fullStr | Role of malaria exposure and off-target responses on RTS,S/AS02A vaccine immunogenicity and protection in Mozambican children |
| title_full_unstemmed | Role of malaria exposure and off-target responses on RTS,S/AS02A vaccine immunogenicity and protection in Mozambican children |
| title_short | Role of malaria exposure and off-target responses on RTS,S/AS02A vaccine immunogenicity and protection in Mozambican children |
| title_sort | role of malaria exposure and off target responses on rts s as02a vaccine immunogenicity and protection in mozambican children |
| url | https://doi.org/10.1038/s41541-025-01167-0 |
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