Heterologous Protection against Malaria after Immunization with Plasmodium falciparum Sporozoites

• Published in: PloS one Vol. 10; no. 5; p. e0124243
• Main Authors: Schats, Remko, Bijker, Else M, van Gemert, Geert-Jan, Graumans, Wouter, van de Vegte-Bolmer, Marga, van Lieshout, Lisette, Haks, Mariëlle C, Hermsen, Cornelus C, Scholzen, Anja, Visser, Leo G, Sauerwein, Robert W
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 01.05.2015; Public Library of Science (PLoS)
• Subjects: Adult; Analysis; Aquatic insects; Bites; Chloroquine; Chloroquine - adverse effects; Chloroquine - therapeutic use; Cloning; Culicidae; Erythrocytes; Health aspects; Hepatitis; Homology; Humans; Immunization; Infection; Infections; Infectious diseases; Insect bites; Liver; Malaria; Malaria, Falciparum - drug therapy; Malaria, Falciparum - immunology; Malaria, Falciparum - parasitology; Malaria, Falciparum - prevention & control; Mosquitoes; Parasitemia - immunology; Parasitemia - parasitology; Parasites; Plasmodium falciparum; Plasmodium falciparum - immunology; Prophylaxis; Sporozoites; Sporozoites - immunology; Vaccines; Vector-borne diseases; Volunteers
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0124243

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. 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 re-challenged with clone NF135.C10 (Cambodia) at 14 months after the last immunization (NCT01660854). 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. 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. Clinicaltrials.gov NCT01660854.