Long lived liver-resident memory T cells of biased specificities for abundant sporozoite antigens drive malaria protection by radiation-attenuated sporozoite vaccination.
Vaccination with radiation-attenuated sporozoites (RAS) can provide highly effective protection against malaria in both humans and mice. To extend understanding of malaria immunity and inform the development of future vaccines, we studied the protective response elicited by this vaccine in C57BL/6 m...
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Public Library of Science (PLoS)
2025-05-01
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| Series: | PLoS Pathogens |
| Online Access: | https://doi.org/10.1371/journal.ppat.1012731 |
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| author | Maria N de Menezes Zhengyu Ge Anton Cozijnsen Stephanie Gras Patrick Bertolino Irina Caminschi Mireille H Lahoud Katsuyuki Yui Geoffrey I McFadden Lynette Beattie William R Heath Daniel Fernandez-Ruiz |
| author_facet | Maria N de Menezes Zhengyu Ge Anton Cozijnsen Stephanie Gras Patrick Bertolino Irina Caminschi Mireille H Lahoud Katsuyuki Yui Geoffrey I McFadden Lynette Beattie William R Heath Daniel Fernandez-Ruiz |
| author_sort | Maria N de Menezes |
| collection | DOAJ |
| description | Vaccination with radiation-attenuated sporozoites (RAS) can provide highly effective protection against malaria in both humans and mice. To extend understanding of malaria immunity and inform the development of future vaccines, we studied the protective response elicited by this vaccine in C57BL/6 mice. We reveal that successive doses of Plasmodium berghei RAS favour the generation of liver CD8+ tissue-resident memory T cells (TRM cells) over circulating memory cells and markedly enhance their longevity. Importantly, RAS immunisation strongly skews the composition of the liver CD8+ TRM compartment towards cells specific for abundant sporozoite antigens, such as thrombospondin-related anonymous protein (TRAP) and circumsporozoite protein (CSP), which become major mediators of protection. The increased prevalence of sporozoite specificities is associated with limited intrahepatic attenuated parasite development and inhibition of naïve T cell responses to all parasite antigens, whether formerly encountered or not, in previously vaccinated mice. This leads to the exclusive expansion of effector T cells formed upon initial immunisation, ultimately reducing the diversity of the liver TRM pool later established. However, stronger responses to less abundant epitopes can be achieved with higher initial doses of RAS. These findings provide novel insights into the mechanisms governing malaria immunity induced by attenuated sporozoite vaccination and highlight the susceptibility of this vaccine to limitations imposed by strain-specific immunity associated with the abundant, yet highly variable sporozoite antigens CSP and TRAP. |
| format | Article |
| id | doaj-art-0afb5c4af75744079a2ff4553bed3e1d |
| institution | Kabale University |
| issn | 1553-7366 1553-7374 |
| language | English |
| publishDate | 2025-05-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS Pathogens |
| spelling | doaj-art-0afb5c4af75744079a2ff4553bed3e1d2025-08-20T03:44:38ZengPublic Library of Science (PLoS)PLoS Pathogens1553-73661553-73742025-05-01215e101273110.1371/journal.ppat.1012731Long lived liver-resident memory T cells of biased specificities for abundant sporozoite antigens drive malaria protection by radiation-attenuated sporozoite vaccination.Maria N de MenezesZhengyu GeAnton CozijnsenStephanie GrasPatrick BertolinoIrina CaminschiMireille H LahoudKatsuyuki YuiGeoffrey I McFaddenLynette BeattieWilliam R HeathDaniel Fernandez-RuizVaccination with radiation-attenuated sporozoites (RAS) can provide highly effective protection against malaria in both humans and mice. To extend understanding of malaria immunity and inform the development of future vaccines, we studied the protective response elicited by this vaccine in C57BL/6 mice. We reveal that successive doses of Plasmodium berghei RAS favour the generation of liver CD8+ tissue-resident memory T cells (TRM cells) over circulating memory cells and markedly enhance their longevity. Importantly, RAS immunisation strongly skews the composition of the liver CD8+ TRM compartment towards cells specific for abundant sporozoite antigens, such as thrombospondin-related anonymous protein (TRAP) and circumsporozoite protein (CSP), which become major mediators of protection. The increased prevalence of sporozoite specificities is associated with limited intrahepatic attenuated parasite development and inhibition of naïve T cell responses to all parasite antigens, whether formerly encountered or not, in previously vaccinated mice. This leads to the exclusive expansion of effector T cells formed upon initial immunisation, ultimately reducing the diversity of the liver TRM pool later established. However, stronger responses to less abundant epitopes can be achieved with higher initial doses of RAS. These findings provide novel insights into the mechanisms governing malaria immunity induced by attenuated sporozoite vaccination and highlight the susceptibility of this vaccine to limitations imposed by strain-specific immunity associated with the abundant, yet highly variable sporozoite antigens CSP and TRAP.https://doi.org/10.1371/journal.ppat.1012731 |
| spellingShingle | Maria N de Menezes Zhengyu Ge Anton Cozijnsen Stephanie Gras Patrick Bertolino Irina Caminschi Mireille H Lahoud Katsuyuki Yui Geoffrey I McFadden Lynette Beattie William R Heath Daniel Fernandez-Ruiz Long lived liver-resident memory T cells of biased specificities for abundant sporozoite antigens drive malaria protection by radiation-attenuated sporozoite vaccination. PLoS Pathogens |
| title | Long lived liver-resident memory T cells of biased specificities for abundant sporozoite antigens drive malaria protection by radiation-attenuated sporozoite vaccination. |
| title_full | Long lived liver-resident memory T cells of biased specificities for abundant sporozoite antigens drive malaria protection by radiation-attenuated sporozoite vaccination. |
| title_fullStr | Long lived liver-resident memory T cells of biased specificities for abundant sporozoite antigens drive malaria protection by radiation-attenuated sporozoite vaccination. |
| title_full_unstemmed | Long lived liver-resident memory T cells of biased specificities for abundant sporozoite antigens drive malaria protection by radiation-attenuated sporozoite vaccination. |
| title_short | Long lived liver-resident memory T cells of biased specificities for abundant sporozoite antigens drive malaria protection by radiation-attenuated sporozoite vaccination. |
| title_sort | long lived liver resident memory t cells of biased specificities for abundant sporozoite antigens drive malaria protection by radiation attenuated sporozoite vaccination |
| url | https://doi.org/10.1371/journal.ppat.1012731 |
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