title: Impact of malaria preexposure on antiparasite cellular and humoral immune responses after controlled human malaria infection.
abstract: To understand the effect of previous malaria exposure on antiparasite immune responses is important for developing successful immunization strategies. Controlled human malaria infections (CHMIs) using cryopreserved Plasmodium falciparum sporozoites provide a unique opportunity to study differences in acquisition or recall of antimalaria immune responses in individuals from different transmission settings and genetic backgrounds. In this study, we compared antiparasite humoral and cellular immune responses in two cohorts of malaria-naive Dutch volunteers and Tanzanians from an area of low malarial endemicity, who were subjected to the identical CHMI protocol by intradermal injection of P. falciparum sporozoites. Samples from both trials were analyzed in parallel in a single center to ensure direct comparability of immunological outcomes. Within the Tanzanian cohort, we distinguished one group with moderate levels of preexisting antibodies to asexual P. falciparum lysate and another that, based on P. falciparum serology, resembled the malaria-naive Dutch cohort. Positive P. falciparum serology at baseline was associated with a lower parasite density at first detection by quantitative PCR (qPCR) after CHMI than that for Tanzanian volunteers with negative serology. Post-CHMI, both Tanzanian groups showed a stronger increase in anti-P. falciparum antibody titers than Dutch volunteers, indicating similar levels of B-cell memory independent of serology. In contrast to the Dutch, Tanzanians failed to increase P. falciparum-specific in vitro recall gamma interferon (IFN-γ) production after CHMI, and innate IFN-γ responses were lower in P. falciparum lysate-seropositive individuals than in seronegative individuals. In conclusion, positive P. falciparum lysate serology can be used to identify individuals with better parasite control but weaker IFN-γ responses in circulating lymphocytes, which may help to stratify volunteers in future CHMI trials in areas where malaria is endemic.
authors.affiliation: Radboud University Medical Center, Department of Medical Microbiology, Nijmegen, The Netherlands.
authors.forename: Joshua M
authors.initials: JM
authors.lastname: Obiero
authors.affiliation: Ifakara Health Institute, Bagamoyo Research and Training Center, Bagamoyo, Tanzania.
authors.forename: Seif
authors.initials: S
authors.lastname: Shekalaghe
authors.affiliation: Radboud University Medical Center, Department of Medical Microbiology, Nijmegen, The Netherlands.
authors.forename: Cornelus C
authors.initials: CC
authors.lastname: Hermsen
authors.affiliation: Ifakara Health Institute, Bagamoyo Research and Training Center, Bagamoyo, Tanzania.
authors.forename: Maxmillian
authors.initials: M
authors.lastname: Mpina
authors.affiliation: Radboud University Medical Center, Department of Medical Microbiology, Nijmegen, The Netherlands.
authors.forename: Else M
authors.initials: EM
authors.lastname: Bijker
authors.affiliation: Radboud University Medical Center, Department of Medical Microbiology, Nijmegen, The Netherlands.
authors.forename: Meta
authors.initials: M
authors.lastname: Roestenberg
authors.affiliation: Radboud University Medical Center, Department of Medical Microbiology, Nijmegen, The Netherlands.
authors.forename: Karina
authors.initials: K
authors.lastname: Teelen
authors.affiliation: Sanaria Inc., Rockville, Maryland, USA.
authors.forename: Peter F
authors.initials: PF
authors.lastname: Billingsley
authors.affiliation: Sanaria Inc., Rockville, Maryland, USA.
authors.forename: B Kim Lee
authors.initials: BK
authors.lastname: Sim
authors.affiliation: Sanaria Inc., Rockville, Maryland, USA.
authors.forename: Eric R
authors.initials: ER
authors.lastname: James
authors.affiliation: Swiss Tropical and Public Health Institute, Department of Medical Parasitology and Infection Biology, Basel, Switzerland University of Basel, Basel, Switzerland.
authors.forename: Claudia A
authors.initials: CA
authors.lastname: Daubenberger
authors.affiliation: Sanaria Inc., Rockville, Maryland, USA.
authors.forename: Stephen L
authors.initials: SL
authors.lastname: Hoffman
authors.affiliation: Ifakara Health Institute, Bagamoyo Research and Training Center, Bagamoyo, Tanzania.
authors.forename: Salim
authors.initials: S
authors.lastname: Abdulla
authors.affiliation: Radboud University Medical Center, Department of Medical Microbiology, Nijmegen, The Netherlands robert.sauerwein@radboudumc.nl anja.scholzen@radboudumc.nl.
authors.forename: Robert W
authors.initials: RW
authors.lastname: Sauerwein
authors.affiliation: Radboud University Medical Center, Department of Medical Microbiology, Nijmegen, The Netherlands robert.sauerwein@radboudumc.nl anja.scholzen@radboudumc.nl.
authors.forename: Anja
authors.initials: A
authors.lastname: Scholzen
mesh_terms: D000328:Adult; D000913:Antibodies, Protozoan / Q000097:blood; D006801:Humans; D007111:Immunity, Cellular; D056724:Immunity, Humoral; D007371:Interferon-gamma / Q000378:metabolism; D007963:Leukocytes, Mononuclear / Q000276:immunology; D016778:Malaria, Falciparum / Q000276:immunology*; D009426:Netherlands; D010963:Plasmodium falciparum / Q000276:immunology*; D013636:Tanzania; D055815:Young Adult
chemical_list: D000913:Antibodies, Protozoan; D007371:Interferon-gamma