The effect of adjuvants on the immune response induced by a DBL4ɛ-ID4 VAR2CSA based Plasmodium falciparum vaccine against placental malaria

• Published in: Vaccine Vol. 30; no. 3; pp. 572 - 579
• Main Authors: Pinto, V.V., Salanti, A., Joergensen, L.M., Dahlbäck, M., Resende, M., Ditlev, S.B., Agger, E.M., Arnot, D.E., Theander, T.G., Nielsen, M.A.
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier Ltd 11.01.2012
• Subjects: adjuvants; Adjuvants, Immunologic - administration & dosage; Animals; antibodies; Antibodies, Protozoan - blood; Antigens, Protozoan - immunology; Cell Adhesion; chondroitin sulfate; Chondroitin Sulfates - metabolism; Chondroitin sulphate A; clinical trials; DBL4ɛ-ID4; Disease Models, Animal; epitopes; Female; humans; immune response; immunoglobulin G; malaria; Malaria Vaccines - administration & dosage; Malaria Vaccines - immunology; Malaria, Falciparum - prevention & control; parasites; Placenta Diseases - prevention & control; Placental malaria vaccine; Plasmodium falciparum; Pregnancy; Rats; Rats, Wistar; vaccines; VAR2CSA; women; CSA; Plasmodium falciparum; FCA; DBL4ɛ-ID4; VAR2CSA; Chondroitin sulphate A; PM; Placental malaria vaccine; DBL; FIA
• ISSN: 0264-410X; 1873-2518
• DOI: 10.1016/j.vaccine.2011.11.068

► Antibodies against the DBL4ɛ-ID4 subunit of the VAR2CSA protein can inhibit parasite binding to the placental ligand chondroitin sulphate A. ► We tested the ability of DBL4ɛ-ID4 to induce binding-inhibitory antibodies when formulated with adjuvants approved for human use. ► We have characterized the immune response of DBL4ɛ-ID4 in combination with Freund's adjuvant, Montanide® ISA 720, Alhydrogel® and CAF01. ► The results demonstrate that the DBL4ɛ-ID4 antigen is highly immunogenic and that binding inhibitory antibodies are induced when formulated with any of the tested adjuvants. A vaccine protecting women against placental malaria could be based on the sub-domains of the VAR2CSA antigen, since antibodies against the DBL4ɛ-ID4 subunit of the VAR2CSA protein can inhibit parasite binding to the placental ligand chondroitin sulphate A (CSA). Here we tested the ability of DBL4ɛ-ID4 to induce binding-inhibitory antibodies when formulated with adjuvants approved for human use. We have characterized the immune response of DBL4ɛ-ID4 in combination with Freund's complete and incomplete adjuvant and with three adjuvants currently being used in clinical trials: Montanide® ISA 720, Alhydrogel® and CAF01. Antibodies induced against DBL4ɛ-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 DBL4ɛ-ID4 antigen. These results demonstrate that the DBL4ɛ-ID4 antigen is highly immunogenic and that binding inhibitory antibodies are induced when formulated with any of the tested adjuvants.