Heterologous Protection against Malaria after Immunization with Plasmodium falciparum Sporozoites.
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 re-challenged 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.


CONCLUSIONS
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.


BACKGROUND
Clinicaltrials.gov NCT01660854.
Leiden University Medical Center, Department of Infectious Diseases, PO Box 9600, 2300 RC, Leiden, The Netherlands.
Remko
R
Schats
Radboud university medical center, Department of Medical Microbiology, PO Box 9101, 6500 HB, Nijmegen, The Netherlands.
Else M
EM
Bijker
Radboud university medical center, Department of Medical Microbiology, PO Box 9101, 6500 HB, Nijmegen, The Netherlands.
Geert-Jan
GJ
van Gemert
Radboud university medical center, Department of Medical Microbiology, PO Box 9101, 6500 HB, Nijmegen, The Netherlands.
Wouter
W
Graumans
Radboud university medical center, Department of Medical Microbiology, PO Box 9101, 6500 HB, Nijmegen, The Netherlands.
Marga
M
van de Vegte-Bolmer
Leiden University Medical Center, Department of Medical Microbiology, PO Box 9600, 2300 RC, Leiden, The Netherlands; Leiden University Medical Center, Department of Parasitology, PO Box 9600, 2300 RC, Leiden, The Netherlands.
Lisette
L
van Lieshout
Leiden University Medical Center, Department of Infectious Diseases, PO Box 9600, 2300 RC, Leiden, The Netherlands.
Mariëlle C
MC
Haks
Radboud university medical center, Department of Medical Microbiology, PO Box 9101, 6500 HB, Nijmegen, The Netherlands.
Cornelus C
CC
Hermsen
Radboud university medical center, Department of Medical Microbiology, PO Box 9101, 6500 HB, Nijmegen, The Netherlands.
Anja
A
Scholzen
Leiden University Medical Center, Department of Infectious Diseases, PO Box 9600, 2300 RC, Leiden, The Netherlands.
Leo G
LG
Visser
Radboud university medical center, Department of Medical Microbiology, PO Box 9101, 6500 HB, Nijmegen, The Netherlands.
Robert W
RW
Sauerwein
D000328:Adult; D002738:Chloroquine / Q000009:adverse effects / Q000627:therapeutic use; D006801:Humans; D007114:Immunization; D016778:Malaria, Falciparum / Q000188:drug therapy / Q000276:immunology* / Q000469:parasitology / Q000517:prevention & control*; D018512:Parasitemia / Q000276:immunology / Q000469:parasitology; D010963:Plasmodium falciparum / Q000276:immunology*; D034101:Sporozoites / Q000276:immunology*
D002738:Chloroquine