High Sporozoite Antibody Titers in Conjunction with Microscopically Detectable Blood Infection Display Signatures of Protection from Clinical Malaria.
Offeddu V., Olotu A., Osier F., Marsh K., Matuschewski K., Thathy V.
Immunoepidemiological studies typically reveal slow, age-dependent acquisition of immune responses againstPlasmodium falciparumsporozoites. Naturally acquired immunity against preerythrocytic stages is considered inadequate to confer protection against clinical malaria. To explore previously unrecognized antisporozoite responses, we measured serum levels of naturally acquired antibodies to wholePlasmodium falciparumsporozoites (Pfspz) and the immunodominant (NANP)5repeats 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 antisporozoite immunity with incidence of clinical malaria. Although naturally acquired humoral responses againstPfspz and (NANP)5were strongly correlated (p < 0.0001), 37% ofPfspz responders did not recognize (NANP)5. The prevalence and magnitude of antisporozoite responses increased with age, although some highPfspz responders were identified among children. Survival analysis revealed a reduced risk of and increased time to first or only episode of clinical malaria amongPfspz or (NANP)5responders carrying microscopically detectablePlasmodium falciparum(Pf) parasitemia 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 anti-(NANP)5(p = 0.001) antibody levels and microscopically detectablePfparasitemia on the risk of subsequent clinical malaria. Our findings indicate that robust antisporozoite 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 preerythrocytic immunity might indeed contribute to protection in nature.