title: A role for immune responses against non-CS components in the cross-species protection induced by immunization with irradiated malaria sporozoites.
abstract: Immunization with irradiated Plasmodium sporozoites induces sterile immunity in rodents, monkeys and humans. The major surface component of the sporozoite the circumsporozoite protein (CS) long considered as the antigen predominantly responsible for this immunity, thus remains the leading candidate antigen for vaccines targeting the parasite's pre-erythrocytic (PE) stages. However, this role for CS was questioned when we recently showed that immunization with irradiated sporozoites (IrrSpz) of a P. berghei line whose endogenous CS was replaced by that of P. falciparum still conferred sterile protection against challenge with wild type P. berghei sporozoites. In order to investigate the involvement of CS in the cross-species protection recently observed between the two rodent parasites P. berghei and P. yoelii, we adopted our gene replacement approach for the P. yoelii CS and exploited the ability to conduct reciprocal challenges. Overall, we found that immunization led to sterile immunity irrespective of the origin of the CS in the immunizing or challenge sporozoites. However, for some combinations, immune responses to CS contributed to the acquisition of protective immunity and were dependent on the immunizing IrrSpz dose. Nonetheless, when data from all the cross-species immunization/challenges were considered, the immune responses directed against non-CS parasite antigens shared by the two parasite species played a major role in the sterile protection induced by immunization with IrrSpz. This opens the perspective to develop a single vaccine formulation that could protect against multiple parasite species.
authors.affiliation: Singapore Immunology Network (SIgN), Agency for Science, Technology and Research (A*STAR), Biopolis, Singapore.
authors.forename: Marjorie
authors.initials: M
authors.lastname: Mauduit
authors.forename: Anne Charlotte
authors.initials: AC
authors.lastname: Grüner
authors.forename: Rita
authors.initials: R
authors.lastname: Tewari
authors.forename: Nadya
authors.initials: N
authors.lastname: Depinay
authors.forename: Michèle
authors.initials: M
authors.lastname: Kayibanda
authors.forename: Jean-Marc
authors.initials: JM
authors.lastname: Chavatte
authors.forename: Jean-François
authors.initials: JF
authors.lastname: Franetich
authors.forename: Andrea
authors.initials: A
authors.lastname: Crisanti
authors.forename: Dominique
authors.initials: D
authors.lastname: Mazier
authors.forename: Georges
authors.initials: G
authors.lastname: Snounou
authors.forename: Laurent
authors.initials: L
authors.lastname: Rénia
mesh_terms: D000818:Animals; D000913:Antibodies, Protozoan / Q000276:immunology; D000953:Antigens, Protozoan / Q000276:immunology; D005260:Female; D007107:Immune System; D007074:Immunoglobulin G / Q000378:metabolism; D007075:Immunoglobulin M / Q000378:metabolism; D008288:Malaria / Q000276:immunology; D017780:Malaria Vaccines / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D010962:Plasmodium berghei / Q000276:immunology* / Q000378:metabolism; D010967:Plasmodium yoelii / Q000276:immunology* / Q000378:metabolism; D015800:Protozoan Proteins / Q000276:immunology / Q000502:physiology*; D034101:Sporozoites / Q000276:immunology
chemical_list: D000913:Antibodies, Protozoan; D000953:Antigens, Protozoan; D007074:Immunoglobulin G; D007075:Immunoglobulin M; D017780:Malaria Vaccines; D015800:Protozoan Proteins; C041595:circumsporozoite protein, Protozoan