Immunogenicity and Efficacy Trials with Plasmodium falciparum Recombinant Antigens Identified as Targets of Opsonizing Antibodies in the Naive Squirrel Monkey Saimiri sciureus

Ronald PerrautInstitut Pasteur de la Guyane Francaise, Institut Pasteur de Paris, Cayenne, French Guiana, France

Search for other papers by Ronald Perraut in
Current site
Google Scholar
PubMed
Close
,
Odile Mercereau-PuijalonInstitut Pasteur de la Guyane Francaise, Institut Pasteur de Paris, Cayenne, French Guiana, France

Search for other papers by Odile Mercereau-Puijalon in
Current site
Google Scholar
PubMed
Close
,
Denise MatteiInstitut Pasteur de la Guyane Francaise, Institut Pasteur de Paris, Cayenne, French Guiana, France

Search for other papers by Denise Mattei in
Current site
Google Scholar
PubMed
Close
,
Eliane BourreauInstitut Pasteur de la Guyane Francaise, Institut Pasteur de Paris, Cayenne, French Guiana, France

Search for other papers by Eliane Bourreau in
Current site
Google Scholar
PubMed
Close
,
Serge BonnefoyInstitut Pasteur de la Guyane Francaise, Institut Pasteur de Paris, Cayenne, French Guiana, France

Search for other papers by Serge Bonnefoy in
Current site
Google Scholar
PubMed
Close
,
Bernard BonnemainsInstitut Pasteur de la Guyane Francaise, Institut Pasteur de Paris, Cayenne, French Guiana, France

Search for other papers by Bernard Bonnemains in
Current site
Google Scholar
PubMed
Close
,
Jurg GysinInstitut Pasteur de la Guyane Francaise, Institut Pasteur de Paris, Cayenne, French Guiana, France

Search for other papers by Jurg Gysin in
Current site
Google Scholar
PubMed
Close
,
Jean-Claude MichelInstitut Pasteur de la Guyane Francaise, Institut Pasteur de Paris, Cayenne, French Guiana, France

Search for other papers by Jean-Claude Michel in
Current site
Google Scholar
PubMed
Close
, and
Luiz Pereira Da SilvaInstitut Pasteur de la Guyane Francaise, Institut Pasteur de Paris, Cayenne, French Guiana, France

Search for other papers by Luiz Pereira Da Silva in
Current site
Google Scholar
PubMed
Close
Restricted access

We have previously shown that Plasmodium falciparum recombinant antigens PfEB200, R23, and Pfi72 consistently inhibit opsonization of infected red blood cells by protective hyperimmune Saimiri sera, indicating that they present target epitopes involved in the phagocytosis of infected red blood cells. We report here an analysis of the immune response elicited in naive squirrel monkeys injected with the individual recombinant antigens or with a mixture of the three antigens combined with a synthetic peptide. In the three administration protocols investigated, there was no evidence for the production of antibody contributing to the phagocytosis of infected red blood cells, contrasting with the increase of opsonizing antibodies elicited by these antigens in monkeys with a prior (≥ 500 days) experience with malaria infection. However, the recombinant antigens were highly immunogenic, inducing specific antibody responses to P. falciparum and to the recombinant antigens. When the monkeys immunized with the antigen combination were challenged with blood-stage parasites, there was substantial protection: three of seven immunized animals self-cured and two others experienced a delayed peak of parasitemia. Taken together with our previous findings, these results suggest that PfEB200, R23, and Pfi72 constitute interesting vaccine candidates, and show that the presence of antibodies promoting phagocytosis of infected red blood cells is not a prerequisite for protection after immunization with these antigens in the Saimiri model.

Save