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Immunization of malaria pre-exposed volunteers with PfSPZ Vaccine elicits long-lived IgM invasion-inhibitory and complement-fixing antibodies

Zenklusen, Isabelle and Jongo, Said and Abdulla, Salim and Ramadhani, Kamaka and Lee Sim, B. Kim and Cardamone, Hayley and Flannery, Erika L. and Nguyen, Thao and Fishbaugher, Matthew and Steel, Ryan W. J. and Betz, Will and Carmago, Nelly and Mikolajczak, Sebastian and Kappe, Stefan H. I. and Hoffman, Stephen L. and Sack, Brandon K. and Daubenberger, Claudia. (2018) Immunization of malaria pre-exposed volunteers with PfSPZ Vaccine elicits long-lived IgM invasion-inhibitory and complement-fixing antibodies. Journal of infectious diseases, 217 (10). pp. 1569-1578.

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Official URL: https://edoc.unibas.ch/64896/

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Abstract

The assessment of antibody responses after immunization with radiation-attenuated, aseptic, purified, cryopreserved Plasmodium falciparum sporozoites (Sanaria PfSPZ Vaccine) has focused on IgG isotype antibodies. Here, we aimed to investigate if P. falciparum sporozoite binding and invasion-inhibitory IgM antibodies are induced following immunization of malaria-preexposed volunteers with PfSPZ Vaccine.; Using serum from volunteers immunized with PfSPZ, we measured vaccine-induced IgG and IgM antibodies to P. falciparum circumsporozoite protein (PfCSP) via ELISA. Function of this serum as well as IgM antibody fractions was measured via in vitro in an inhibition of sporozoite invasion assay. These IgM antibody fractions were also measured for binding to sporozoites by immunofluorescence assay and complement fixation on whole sporozoites.; We found that in addition to anti-PfCSP IgG, malaria-preexposed volunteers developed anti-PfCSP IgM antibodies after immunization with PfSPZ Vaccine and that these IgM antibodies inhibited P. falciparum sporozoite invasion of hepatocytes in vitro. These IgM plasma fractions also fixed complement to whole P. falciparum sporozoites.; This is the first finding that PfCSP and P. falciparum sporozoite-binding IgM antibodies are induced following immunization of PfSPZ Vaccine in malaria-preexposed individuals and that IgM antibodies can inhibit P. falciparum sporozoite invasion into hepatocytes in vitro and fix complement on sporozoites. These findings indicate that the immunological assessment of PfSPZ Vaccine-induced antibody responses could be more sensitive if they include parasite-specific IgM in addition to IgG antibodies.; NCT02132299.
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:Zenklusen, Isabelle and Daubenberger, Claudia
Item Type:Article, refereed
Article Subtype:Research Article
Publisher:Oxford University Press
ISSN:0022-1899
Note:Publication type according to Uni Basel Research Database: Journal article
Identification Number:
Last Modified:03 Jul 2018 10:38
Deposited On:03 Jul 2018 10:38

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