High Sporozoite Antibody Titers in Conjunction with Microscopically Detectable Blood Infection Display Signatures of Protection from Clinical Malaria

Résumé

Immuno-epidemiological studies typically reveal slow, age-dependent acquisition of immune responses against Plasmodium falciparum sporozoites. Naturally acquired immunity against pre-erythrocytic stages is considered inadequate to confer protection against clinical malaria. To explore previously unrecognized anti-sporozoite responses, we measured serum levels of naturally acquired antibodies to whole Plasmodium falciparum sporozoites (Pfspz) and the immunodominant (NANP)5-repeats of the major sporozoite surface protein, circumsporozoite protein, in a well-characterized Kenyan cohort. Sera were sampled at the start of the malaria transmission season and all subjects were prospectively monitored for uncomplicated clinical malaria in the ensuing 6 months. We used Kaplan-Meier analysis and multivariable regression to investigate the association of anti-sporozoite immunity with incidence of clinical malaria. Although naturally acquired humoral responses against Pfspz and (NANP)5 were strongly correlated (p<0.0001), 37% of Pfspz-responders did not recognize (NANP)5. The prevalence and magnitude of anti-sporozoite responses increased with age, although some high Pfspz-responders were identified among children. Survival analysis revealed a reduced risk of and increased time to first or only episode of clinical malaria among Pfspz- or (NANP)5-responders carrying microscopically detectable Pf parasitaemia at the start of the transmission season (p<0.03. Our Cox regression interaction models indicated a potentially protective interaction between high anti-Pfspz (p=0.002) or (NANP)5 (p=0.001) antibody levels and microscopically detectable Pf parasitaemia on the risk of subsequent clinical malaria. Our findings indicate that robust anti-sporozoite immune responses can be naturally acquired already at an early age. A potentially protective role of high levels of anti-Pfspz antibodies against clinical episodes of uncomplicated malaria was detected, suggesting that antibody-mediated pre-erythrocytic immunity might indeed contribute to protection in nature.

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