Sterile protection against malaria is independent of immune responses to the circumsporozoite protein

Anne Charlotte Grüner, Marjorie Mauduit, Rita Tewari, Jackeline F. Romero, Nadya Depinay, Michèle Kayibanda, Eliette Lallemand, Jean Marc Chavatte, Andrea Crisanti, Photini Sinnis, Dominique Mazier, Giampietro Corradin, Georges Snounou, Laurent Rénia

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Abstract

Background. Research aimed at developing vaccines against infectious diseases generally seeks to induce robust immune responses to immunodominant antigens. This approach has led to a number of efficient bacterial and viral vaccines, but it has yet to do so for parasitic pathogens. For malaria, a disease of global importance due to infection by Plasmodium protozoa, immunization with radiation-attenuated sporozoites uniquely leads to long lasting sterile immunity against infection, The circumsporozoite protein (CSP), an important component of the sporozoite's surface, remains the leading candidate antigen for vaccines targeting the parasite's pre-erythrocytic stages. Difficulties in developing CSP-based vaccines that reproduce the levels of protection afforded by radiation-attenuated sporozoites have led us to question the role of CSP in the acquisition of sterile immunity. We have used a parasite transgenic for the CSP because it allowed us to test whether a major immunodominant Plasmodium antigen is indeed need for the induction of protective immunity against infection. Methology/Main Findings. We employed a P. berghei parasite line that expresses a heterologous CSP from P. falciparum in order to assess the role of the CSP in the protection conferred by vaccination with radiation-attenuated P. berghei parasites. Our data demonstrated that sterile immunity could be obtained despite the absence of immune responses specific to the CSP expressed by the parasite used for challenge. Conclusions. We conclude that other pre-erythrocytic parasite antigens, possibly hitherto uncharacterised, can be targeted to induce sterile immunity against malaria. From a broader perspective, our results raise the question as to whether immunodominant parasite antigens should be the favoured targets for vaccine development.

Original languageEnglish (US)
Article numbere1371
JournalPloS one
Volume2
Issue number12
DOIs
StatePublished - Dec 26 2007

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)
  • General

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    Grüner, A. C., Mauduit, M., Tewari, R., Romero, J. F., Depinay, N., Kayibanda, M., Lallemand, E., Chavatte, J. M., Crisanti, A., Sinnis, P., Mazier, D., Corradin, G., Snounou, G., & Rénia, L. (2007). Sterile protection against malaria is independent of immune responses to the circumsporozoite protein. PloS one, 2(12), [e1371]. https://doi.org/10.1371/journal.pone.0001371