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.