1. Immunization of Malaria-Preexposed Volunteers With PfSPZ Vaccine Elicits Long-Lived IgM Invasion-Inhibitory and Complement-Fixing Antibodies
- Author
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Will Betz, Thao Nguyen, Stefan H. I. Kappe, Nelly Carmago, Isabelle Zenklusen, Hayley Cardamone, Brandon K. Sack, Claudia Daubenberger, Salim Abdulla, Sebastian A. Mikolajczak, Kamaka Ramadhani, Stephen L. Hoffman, Said Jongo, B. Kim Lee Sim, Ryan W.J. Steel, Matthew Fishbaugher, and Erika L. Flannery
- Subjects
0301 basic medicine ,Adult ,Male ,Volunteers ,Plasmodium falciparum ,Antibodies, Protozoan ,Vaccines, Attenuated ,Immunoglobulin G ,03 medical and health sciences ,Young Adult ,Major Articles and Brief Reports ,0302 clinical medicine ,Double-Blind Method ,parasitic diseases ,Malaria Vaccines ,Immunology and Allergy ,Medicine ,Humans ,030212 general & internal medicine ,Malaria, Falciparum ,biology ,business.industry ,Vaccination ,Complement fixation test ,biology.organism_classification ,Virology ,PfSPZ vaccine ,Malaria ,Circumsporozoite protein ,030104 developmental biology ,Infectious Diseases ,Immunization ,Immunoglobulin M ,Sporozoites ,Antibody Formation ,biology.protein ,Antibody ,business - 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.
- Published
- 2017