Full-length plasmodium falciparum circumsporozoite protein administered with long-chain poly(I·C) or the toll-like receptor 4 agonist glucopyranosyl lipid adjuvant-stable emulsion elicits potent antibody and CD4+ T cell immunity and protection in mice

Kathrin Kastenmüller, Diego A. Espinosa, Lauren Trager, Cristina Stoyanov, Andres M. Salazar, Santosh Pokalwar, Sanjay Singh, Sheetij Dutta, Christian F. Ockenhouse, Fidel Zavala, Robert A. Sedera

Research output: Contribution to journalArticle

Abstract

The Plasmodium falciparum circumsporozoite (CS) protein (CSP) is a major vaccine target for preventing malaria infection. Thus, developing strong and durable antibody and T cell responses against CSP with novel immunogens and potent adjuvants may improve upon the success of current approaches. Here, we compare four distinct full-length P. falciparum CS proteins expressed in Escherichia coli or Pichia pastoris for their ability to induce immunity and protection in mice when administered with long-chain poly(I·C) [poly(I·C)LC] as an adjuvant. CS proteins expressed in E. coli induced high-titer antibody responses against the NANP repeat region and potent CSP-specific CD4+ T cell responses. Moreover, E. coli-derived CS proteins in combination with poly(I·C)LC induced potent multifunctional (interleukin 2-positive [IL-2+], tumor necrosis factor alpha-positive [TNF-α+], gamma interferon-positive [IFN-γ+]) CD4+ effector T cell responses in blood, in spleen, and particularly in liver. Using transgenic Plasmodium berghei expressing the repeat region of P. falciparum CSP [Pb-CS(Pf)], we showed that there was a 1-to 4-log decrease in malaria rRNA in the liver following a high-dose challenge and+50% sterilizing protection with a lowdose challenge compared to control levels. Protection was directly correlated with high-level antibody titers but not CD4+ T cell responses. Finally, protective immunity was also induced using the Toll-like receptor 4 agonist glucopyranosyl lipid adjuvantstable emulsion (GLA-SE) as the adjuvant, which also correlated with high antibody titers yet CD4+ T cell immunity that was significantly less potent than that with poly(I·C)LC. Overall, these data suggest that full-length CS proteins and poly(I·C)LC or GLA-SE offer a simple vaccine formulation to be used alone or in combination with other vaccines for preventing malaria infection.

Original languageEnglish (US)
Pages (from-to)789-800
Number of pages12
JournalInfection and immunity
Volume81
Issue number3
DOIs
StatePublished - Mar 1 2013

ASJC Scopus subject areas

  • Parasitology
  • Microbiology
  • Immunology
  • Infectious Diseases

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