Background: Sterile protection in >90% of volunteers against homologous Plasmodium falciparum infection has been achieved only using the controlled human malaria infection (CHMI) model. This efficient model involves whole parasite immunizations under chloroquine prophylaxis (CPS-immunization), requiring only 30-45 mosquitoes bites infected with P. falciparum-sporozoites. Given the large diversity of P. falciparum parasites, it is essential to assess protection against heterologous parasite strains. Methods: In an open-label follow-up study, 16 volunteers previously CPS-immunized and challenged with P. falciparum NF54 (West-Africa) in a dose de-escalation and challenge trial were rechallenged with clone NF135.C10 (Cambodia) at 14 months after the last immunization (NCT01660854). Results: Two out of thirteen NF54 protected volunteers previously fully protected against NF54 were also fully protected against NF135.C10, while 11/13 showed a delayed patency (median prepatent period of 10.5 days (range 9.0-15.5) versus 8.5 days in 5 malaria-naïve controls (p = 0.0005). Analysis of patency by qPCR indicated a 91 to >99% estimated reduction of liver parasite load in 7/11 partially protected subjects. Three volunteers previously not protected against NF54, were also not protected against NF135.C10. Conclusion: This study shows that CPS-immunization can induce heterologous protection for a period of more than one year, which is a further impetus for clinical development of whole parasite vaccines. Trial Registration: Clinicaltrials.gov NCT01660854
CITATION STYLE
Schats, R., Bijker, E. M., Van Gemert, G. J., Graumans, W., Van De Vegte-Bolmer, M., Van Lieshout, L., … Sauerweina, R. W. (2015). Heterologous Protection against Malaria after Immunization with Plasmodium falciparum Sporozoites. PLoS ONE, 10(5). https://doi.org/10.1371/journal.pone.0124243
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