title: Sterile protection against malaria is independent of immune responses to the circumsporozoite protein.
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 needed for the induction of sterile protective immunity against infection.
  
  
  RESULTS
  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.
authors.affiliation: Institut Cochin, Department of Immunology, Université Paris Descartes, Centre National de Recherche Scientifique (CNRS) UMR 8104, Paris, France.
authors.forename: Anne Charlotte
authors.initials: AC
authors.lastname: Grüner
authors.forename: Marjorie
authors.initials: M
authors.lastname: Mauduit
authors.forename: Rita
authors.initials: R
authors.lastname: Tewari
authors.forename: Jackeline F
authors.initials: JF
authors.lastname: Romero
authors.forename: Nadya
authors.initials: N
authors.lastname: Depinay
authors.forename: Michèle
authors.initials: M
authors.lastname: Kayibanda
authors.forename: Eliette
authors.initials: E
authors.lastname: Lallemand
authors.forename: Jean-Marc
authors.initials: JM
authors.lastname: Chavatte
authors.forename: Andrea
authors.initials: A
authors.lastname: Crisanti
authors.forename: Photini
authors.initials: P
authors.lastname: Sinnis
authors.forename: Dominique
authors.initials: D
authors.lastname: Mazier
authors.forename: Giampietro
authors.initials: G
authors.lastname: Corradin
authors.forename: Georges
authors.initials: G
authors.lastname: Snounou
authors.forename: Laurent
authors.initials: L
authors.lastname: Rénia
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D004797:Enzyme-Linked Immunosorbent Assay; D005455:Fluorescent Antibody Technique; D016778:Malaria, Falciparum / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008969:Molecular Sequence Data; D015800:Protozoan Proteins / Q000737:chemistry / Q000276:immunology*; D017386:Sequence Homology, Amino Acid
chemical_list: D015800:Protozoan Proteins; C041595:circumsporozoite protein, Protozoan