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Impact of malaria preexposure on antiparasite cellular and humoral immune responses after controlled human malaria infection

Obiero, Joshua M. and Shekalaghe, Seif and Hermsen, Cornelus C. and Mpina, Maxmillian and Bijker, Else M. and Roestenberg, Meta and Teelen, Karina and Billingsley, Peter F. and Sim, B. Kim Lee and James, Eric R. and Daubenberger, Claudia A. and Hoffman, Stephen L. and Abdulla, Salim and Sauerwein, Robert W. and Scholzen, Anja. (2015) Impact of malaria preexposure on antiparasite cellular and humoral immune responses after controlled human malaria infection. Infection and immunity, Vol. 83, H. 5. pp. 2185-2196.

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Official URL: http://edoc.unibas.ch/dok/A6381863

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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.
Faculties and Departments:09 Associated Institutions > Swiss Tropical and Public Health Institute (Swiss TPH)
09 Associated Institutions > Swiss Tropical and Public Health Institute (Swiss TPH) > Department of Medical Parasitology and Infection Biology > Clinical Immunology (Daubenberger)
UniBasel Contributors:Daubenberger, Claudia
Item Type:Article, refereed
Article Subtype:Research Article
Bibsysno:Link to catalogue
Publisher:American Society for Microbiology
ISSN:1098-5522
Note:Publication type according to Uni Basel Research Database: Journal article
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Last Modified:05 Jun 2015 08:52
Deposited On:05 Jun 2015 08:52

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