Abstract
Complete sterile protection to Plasmodium falciparum (Pf) infection mediated by pre-erythrocytic immunity can be experimentally induced under chloroquine prophylaxis, through immunization with sporozoites from infected mosquitoes' bites (CPS protocol). To characterize the profile of CPS induced antibody (Ab) responses, we developed a proteome microarray containing 809 Pf antigens showing a distinct Ab profile with recognition of antigens expressed in pre-erythrocytic life-cycle stages. In contrast, plasma from naturally exposed semi-immune individuals from Kenya was skewed toward antibody reactivity against asexual blood stage antigens. CPS-immunized and semi-immune individuals generated antibodies against 192 and 202 Pf antigens, respectively, but only 60 antigens overlapped between the two groups. Although the number of reactive antigens varied between the CPS-immunized individuals, all volunteers reacted strongly against the pre-erythrocytic antigens circumsporozoite protein (CSP) and liver stage antigen 1 (LSA1). Well classified merozoite and erythrocytic antigens were strongly reactive in semi-immune individuals but lacking in the CPS immunized group. These data show that the antibody profile of CPS-immunized and semi-immune groups have quite distinct profiles reflecting their protective immunity; antibodies from CPS immunized individuals react strongly against pre-erythrocytic while semi-immune individuals mainly react against erythrocytic antigens.
Highlights
Complete sterile protection to Plasmodium falciparum (Pf) infection mediated by pre-erythrocytic immunity can be experimentally induced under chloroquine prophylaxis, through immunization with sporozoites from infected mosquitoes’ bites (CPS protocol)
These data show that the antibody profile of ChemoProphylaxis with Sporozoites (CPS)-immunized and semi-immune groups have quite distinct profiles reflecting their protective immunity; antibodies from CPS immunized individuals react strongly against pre-erythrocytic while semi-immune individuals mainly react against erythrocytic antigens
We showed that complete protection against an experimental challenge, can be induced in malarianaıve volunteers using a protocol of ChemoProphylaxis with Sporozoites (CPS)[12], and that this protection is www.nature.com/scientificreports mediated by a pre-erythrocytic immunity[13]
Summary
Complete sterile protection to Plasmodium falciparum (Pf) infection mediated by pre-erythrocytic immunity can be experimentally induced under chloroquine prophylaxis, through immunization with sporozoites from infected mosquitoes’ bites (CPS protocol). Which and how many of the 5,400 possible Pf proteins encoded by the Pf genome[7] elicit protective antibodies remains unclear To address this important knowledge gap, we constructed a protein microarray using Pf-3D7 genomic data which contained 2,320 individual polypeptides representing 1,200 known and hypothetical proteins, or ,23% of the entire Pf proteome[8,9]. In order to better understand the antibody responses induced by this immunization regimen, we developed a new downselected proteome array containing 809 of the reactive antigens recognized in other cohorts2,8,10(Supplementary figure 1) We probed this array with plasma specimens from CPS-immunized individuals and compared the reactivities with that of specimens from adult individuals from Kenya with naturally acquired protective immunity
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