A synthetic TLR4 agonist formulated in an emulsion enhances humoral and Type 1 cellular immune responses against GMZ2 - A GLURP-MSP3 fusion protein malaria vaccine candidate

Research output: Contribution to journalJournal articleResearchpeer-review

  • Susana Lousada-Dietrich
  • Prajakta S Jogdand
  • Søren Jepsen
  • Vera Manuel Valadão Vaz dos Santos Pinto
  • Sisse B Ditlev
  • Michael Christiansen
  • Severin Olesen Larsen
  • Christopher B Fox
  • Vanitha S Raman
  • Randall F Howard
  • Thomas S Vedvick
  • Gregory Ireton
  • Darrick Carter
  • Steven G Reed
  • Theisen, Michael
GMZ2 adjuvanted by aluminum hydroxide is a candidate malaria vaccine that has successfully passed phase 1 clinical testing in adult German and Gabonese volunteers and Gabonese children under five. Here we report a preclinical study screening a series of adjuvant vehicles and Toll-like receptor (TLR) agonists in CB6F1 mice to identify an improved formulation of GMZ2 suitable for further human clinical studies. GMZ2 formulated in an oil-in-water emulsion plus the synthetic TLR4 agonist GLA elicits the highest (a) vaccine-specific IgG2a and total IgG titers, (b) parasite-specific IFA titers, (c) levels of Type 1 cytokine responses (IFN-¿), and (d) number of long-lived-plasma cells (LLPC) secreting antibodies against both the GMZ2 fusion and its two components. Thus, GLA helps to elicit a vaccine-specific Type 1 antibody profile together with high levels of LLPC, both of which are thought to be essential for the development of long-term protective immunity against clinical malaria.
Original languageEnglish
JournalVaccine
Volume29
Issue number17
Pages (from-to)3284-92
Number of pages9
DOIs
Publication statusPublished - 12 Apr 2011

ID: 33325738