Humoral protection against mosquito bite-transmitted Plasmodium falciparum infection in humanized mice

Brandon K. Sack, Sebastian A. Mikolajczak, Matthew Fishbaugher, Ashley M. Vaughan, Erika L. Flannery, Thao Nguyen, Will Betz, Mary Jane Navarro, Lander Foquet, Ryan W.J. Steel, Zachary P. Billman, Sean C. Murphy, Stephen L. Hoffman, Sumana Chakravarty, B. Kim Lee Sim, Marije Behet, Isaie J. Reuling, Jona Walk, Anja Scholzen, Robert W. SauerweinAndrew S. Ishizuka, Barbara Flynn, Robert A. Seder, Stefan H.I. Kappe

Research output: Contribution to journalArticle

12 Scopus citations

Abstract

A malaria vaccine that prevents infection will be an important new tool in continued efforts of malaria elimination, and such vaccines are under intense development for the major human malaria parasite Plasmodium falciparum (Pf). Antibodies elicited by vaccines can block the initial phases of parasite infection when sporozoites are deposited into the skin by mosquito bite and then target the liver for further development. However, there are currently no standardized in vivo preclinical models that can measure the inhibitory activity of antibody specificities against Pf sporozoite infection via mosquito bite. Here, we use human liver-chimeric mice as a challenge model to assess prevention of natural Pf sporozoite infection by antibodies. We demonstrate that these mice are consistently infected with Pf by mosquito bite and that this challenge can be combined with passive transfer of either monoclonal antibodies or polyclonal human IgG from immune serum to measure antibody-mediated blocking of parasite infection using bioluminescent imaging. This methodology is useful to down-select functional antibodies and to investigate mechanisms or immune correlates of protection in clinical trials, thereby informing rational vaccine optimization.

Original languageEnglish (US)
Article number27
Journalnpj Vaccines
Volume2
Issue number1
DOIs
StatePublished - Dec 1 2017

ASJC Scopus subject areas

  • Immunology
  • Pharmacology
  • Infectious Diseases
  • Pharmacology (medical)

Fingerprint Dive into the research topics of 'Humoral protection against mosquito bite-transmitted Plasmodium falciparum infection in humanized mice'. Together they form a unique fingerprint.

  • Cite this

    Sack, B. K., Mikolajczak, S. A., Fishbaugher, M., Vaughan, A. M., Flannery, E. L., Nguyen, T., Betz, W., Jane Navarro, M., Foquet, L., Steel, R. W. J., Billman, Z. P., Murphy, S. C., Hoffman, S. L., Chakravarty, S., Sim, B. K. L., Behet, M., Reuling, I. J., Walk, J., Scholzen, A., ... Kappe, S. H. I. (2017). Humoral protection against mosquito bite-transmitted Plasmodium falciparum infection in humanized mice. npj Vaccines, 2(1), [27]. https://doi.org/10.1038/s41541-017-0028-2