Immunization of Malaria-Preexposed Volunteers With PfSPZ Vaccine Elicits Long-Lived IgM Invasion-Inhibitory and Complement-Fixing Antibodies. (8th February 2018)

• Record Type: Journal Article
• Authors: Zenklusen, Isabelle; Jongo, Said; Abdulla, Salim; Ramadhani, Kamaka; Lee Sim, B Kim; Cardamone, Hayley; Flannery, Erika L; Nguyen, Thao; Fishbaugher, Matthew; Steel, Ryan W J; Betz, Will; Carmago, Nelly; Mikolajczak, Sebastian; Kappe, Stefan H I; Hoffman, Stephen L; Sack, Brandon K; Daubenberger, Claudia
• Is Part Of: Journal of infectious diseases. Volume 217:Number 10(2018)
• Page Start: 1569
• Page End: 1578
• Publication Date: 2018-02-08
• Subjects: malaria -- PfSPZ vaccine -- malaria-preexposed individuals -- functional antibodies -- IgM; Communicable diseases -- Periodicals; Diseases -- Causes and theories of causation -- Periodicals; Medicine -- Periodicals; Communicable Diseases -- Periodicals; Electronic journals; 616.9
• DOI: 10.1093/infdis/jiy080
• Languages: English
• ISSNs: 0022-1899

Abstract

Abstract : We show that functional antisporozoite IgM antibodies are induced in Tanzanian volunteers immunized with radiation attenuated, aseptic, purified, cryopreserved Plasmodium falciparum sporozoites (Sanaria PfSPZ Vaccine), arguing for analysis of this class of antibody in future malaria vaccine trials. Abstract: Background: 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. Methods: 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. Results: 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. Conclusions: 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. Clinical Trials Registration: NCT02132299.