Dataset Information

Quantification of anti-parasite and anti-disease immunity to malaria as a function of age and exposure.

ABSTRACT: Fundamental gaps remain in our understanding of how immunity to malaria develops. We used detailed clinical and entomological data from parallel cohort studies conducted across the malaria transmission spectrum in Uganda to quantify the development of immunity against symptomatic P. falciparum as a function of age and transmission intensity. We focus on: anti-parasite immunity (i.e. ability to control parasite densities) and anti-disease immunity (i.e. ability to tolerate higher parasite densities without fever). Our findings suggest a strong effect of age on both types of immunity, not explained by cumulative-exposure. They also show an independent effect of exposure, where children living in moderate/high transmission settings develop immunity faster as transmission increases. Surprisingly, children in the lowest transmission setting appear to develop immunity more efficiently than those living in moderate transmission settings. Anti-parasite and anti-disease immunity develop in parallel, reducing the probability of experiencing symptomatic malaria upon each subsequent P. falciparum infection.

SUBMITTER: Rodriguez-Barraquer I

PROVIDER: S-EPMC6103767 | biostudies-literature | 2018 Jul

REPOSITORIES: biostudies-literature

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Quantification of anti-parasite and anti-disease immunity to malaria as a function of age and exposure.

Rodriguez-Barraquer Isabel I Arinaitwe Emmanuel E Jagannathan Prasanna P Kamya Moses R MR Rosenthal Phillip J PJ Rek John J Dorsey Grant G Nankabirwa Joaniter J Staedke Sarah G SG Kilama Maxwell M Drakeley Chris C Ssewanyana Isaac I Smith David L DL Greenhouse Bryan B

eLife 20180725

Fundamental gaps remain in our understanding of how immunity to malaria develops. We used detailed clinical and entomological data from parallel cohort studies conducted across the malaria transmission spectrum in Uganda to quantify the development of immunity against symptomatic <i>P. falciparum</i> as a function of age and transmission intensity. We focus on: anti-parasite immunity (i.e. ability to control parasite densities) and anti-disease immunity (i.e. ability to tolerate higher parasite ...[more]

PMID: 30044224

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Project description:Protective immunity against preerythrocytic malaria parasite infection is difficult to achieve. Intracellular Plasmodium parasites likely minimize antigen presentation by surface-expressed major histocompatibility complex class I (MHC-I) molecules on infected cells, yet they actively remodel their host cells by export of parasite factors. Whether exported liver-stage proteins constitute better candidates for MHC-I antigen presentation to CD8(+) T lymphocytes remains unknown. Here, we systematically characterized the contribution of protein export to the magnitude of antigen-specific T-cell responses against Plasmodium berghei liver-stage parasites in C57BL/6 mice. We generated transgenic sporozoites that secrete a truncated ovalbumin (OVA) surrogate antigen only in the presence of an amino-terminal protein export element. Immunization with live attenuated transgenic sporozoites revealed that antigen export was not critical for CD8(+) T-cell priming but enhanced CD8(+) T-cell proliferation in the liver. Upon transfer of antigen-specific CD8(+) T cells, liver-stage parasites secreting the target protein were eliminated more efficiently. We conclude that Plasmodium parasites strictly control protein export during liver infection to minimize immune recognition. Strategies that enhance the discharge of parasite proteins into infected hepatocytes could improve the efficacy of candidate preerythrocytic malaria vaccines. Importance: Vaccine development against Plasmodium parasites remains a priority in malaria research. The most advanced malaria subunit vaccine candidates contain Plasmodium surface proteins with important roles for parasite vital functions. A fundamental question is whether recognition by effector CD8(+) T cells is restricted to sporozoite surface antigens or extends to parasite proteins that are synthesized during the extensive parasite expansion phase in the liver. Using a surrogate model antigen, we found that a cytoplasmic antigen is able to induce robust protective CD8(+) T-cell responses, but protein export further enhances immunogenicity and protection. Our results show that a cytoplasmic localization does not exclude a protein's candidacy for malaria subunit vaccines and that protein secretion can enhance protective immunity.

Dataset Information

Quantification of anti-parasite and anti-disease immunity to malaria as a function of age and exposure.

Publications

Quantification of anti-parasite and anti-disease immunity to malaria as a function of age and exposure.

Similar Datasets

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