The effect of adjuvants on the immune response induced by a DBL4 epsilon-ID4 VAR2CSA based Plasmodium falciparum vaccine against placental malaria

V. V. Pinto, A. Salanti, L. M. Joergensen, M. Dahlback, M. Resende, S. B. Ditlev, E. M. Agger, D. E. Arnot, T. G. Theander, M. A. Nielsen

Research output: Contribution to journalArticlepeer-review

Abstract

A vaccine protecting women against placental malaria could be based on the sub-domains of the VAR2CSA antigen, since antibodies against the DBL4 epsilon-1D4 subunit of the VAR2CSA protein can inhibit parasite binding to the placental ligand chondroitin sulphate A (CSA). Here we tested the ability of DBL4 epsilon-1D4 to induce binding-inhibitory antibodies when formulated with adjuvants approved for human use. We have characterized the immune response of DBL4 epsilon-ID4 in combination with Freund's complete and incomplete adjuvant and with three adjuvants currently being used in clinical trials: Montanide (R) ISA 720, Alhydrogel (R) and CAF01. Antibodies induced against DBL4 epsilon-ID4 in combination with these adjuvants inhibited parasite binding to CSA from 82% to 99%. Although, different epitope recognition patterns were obtained for the different formulations, all adjuvant combinations induced strong Th1 and Th2 type responses, resulting in IgG with similar binding strength, with to the DBL4 epsilon-1D4 antigen. These results demonstrate that the DBL4 epsilon-1D4 antigen is highly immunogenic and that binding inhibitory antibodies are induced when formulated with any of the tested adjuvants.

Original languageEnglish
Pages (from-to)572-579
Number of pages8
JournalVaccine
Volume30
Issue number3
Early online date25 Nov 2011
DOIs
Publication statusPublished - 11 Jan 2012

Keywords

  • Plasmodium falciparum
  • VAR2CSA
  • DBL4e-ID4
  • Placental malaria vaccine
  • Chrondroitin sulphate A

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