Model for in vivo assessment of humoral protection against malaria sporozoite challenge by passive transfer of monoclonal antibodies and immune serum

Brandon K. Sack, Jessica L. Miller, Ashley M. Vaughan, Alyse Douglass, Alexis Kaushansky, Sebastian Mikolajczak, Alida Coppi, Gloria Gonzalez-Aseguinolaza, Moriya Tsuji, Fidel Zavala, Photini Sinnis, Stefan H.I. Kappe

Research output: Contribution to journalArticle

50 Scopus citations

Abstract

Evidence from clinical trials of malaria vaccine candidates suggests that both cell-mediated and humoral immunity to pre-erythrocytic parasite stages can provide protection against infection. Novel pre-erythrocytic antibody (Ab) targets could be key to improving vaccine formulations, which are currently based on targeting antigens such as the circumsporozoite protein (CSP). However, methods to assess the effects of sporozoite-specific Abs on pre-erythrocytic infection in vivo remain underdeveloped. Here, we combined passive transfer of monoclonal Abs (MAbs) or immune serum with a luciferase-expressing Plasmodium yoelii sporozoite challenge to assess Ab-mediated inhibition of liver infection in mice. Passive transfer of a P. yoelii CSP MAb showed inhibition of liver infection when mice were challenged with sporozoites either intravenously or by infectious mosquito bite. However, inhibition was most potent for the mosquito bite challenge, leading to a more significant reduction of liver-stage burden and even a lack of progression to blood-stage parasitemia. This suggests that Abs provide effective protection against a natural infection. Inhibition of liver infection was also achieved by passive transfer of immune serum from whole-parasite-immunized mice. Furthermore, we demonstrated that passive transfer of a MAb against P. falciparum CSP inhibited liver-stage infection in a humanized mouse/P. falciparum challenge model. Together, these models constitute unique and sensitive in vivo methods to assess serum-transferable protection against Plasmodium sporozoite challenge.

Original languageEnglish (US)
Pages (from-to)808-817
Number of pages10
JournalInfection and Immunity
Volume82
Issue number2
DOIs
StatePublished - Feb 1 2014

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ASJC Scopus subject areas

  • Parasitology
  • Microbiology
  • Immunology
  • Infectious Diseases

Cite this

Sack, B. K., Miller, J. L., Vaughan, A. M., Douglass, A., Kaushansky, A., Mikolajczak, S., Coppi, A., Gonzalez-Aseguinolaza, G., Tsuji, M., Zavala, F., Sinnis, P., & Kappe, S. H. I. (2014). Model for in vivo assessment of humoral protection against malaria sporozoite challenge by passive transfer of monoclonal antibodies and immune serum. Infection and Immunity, 82(2), 808-817. https://doi.org/10.1128/IAI.01249-13