Immunization of Malaria-Preexposed Volunteers with PfSPZ Vaccine Elicits Long-Lived IgM Invasion-Inhibitory and Complement-Fixing Antibodies

Isabelle Zenklusen, Said Jongo, Salim Abdulla, Kamaka Ramadhani, B. Kim Lee Sim, Hayley Cardamone, Erika L. Flannery, Thao Nguyen, Matthew Fishbaugher, Ryan W.J. Steel, Will Betz, Nelly Carmago, Sebastian Mikolajczak, Stefan H.I. Kappe, Stephen L. Hoffman, Brandon Wilder, Claudia Daubenberger

Research output: Contribution to journalArticle

18 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)1569-1578
Number of pages10
JournalJournal of Infectious Diseases
Volume217
Issue number10
DOIs
StatePublished - Apr 23 2018
Externally publishedYes

Keywords

  • functional antibodies
  • IgM
  • malaria
  • malaria-preexposed individuals
  • PfSPZ vaccine

ASJC Scopus subject areas

  • Immunology and Allergy
  • Infectious Diseases

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    Zenklusen, I., Jongo, S., Abdulla, S., Ramadhani, K., Lee Sim, B. K., Cardamone, H., Flannery, E. L., Nguyen, T., Fishbaugher, M., Steel, R. W. J., Betz, W., Carmago, N., Mikolajczak, S., Kappe, S. H. I., Hoffman, S. L., Wilder, B., & Daubenberger, C. (2018). Immunization of Malaria-Preexposed Volunteers with PfSPZ Vaccine Elicits Long-Lived IgM Invasion-Inhibitory and Complement-Fixing Antibodies. Journal of Infectious Diseases, 217(10), 1569-1578. https://doi.org/10.1093/infdis/jiy080