The effect of adjuvants on the immune response induced by a DBL4e-ID4 VAR2CSA based Plasmodium falciparum vaccine against placental malaria

TY - JOUR

T1 - The effect of adjuvants on the immune response induced by a DBL4e-ID4 VAR2CSA based Plasmodium falciparum vaccine against placental malaria

AU - Pinto, V V

AU - Salanti, A

AU - Joergensen, L M

AU - Dahlbäck, M

AU - Resende, M

AU - Ditlev, S B

AU - Agger, E M

AU - Arnot, D E

AU - Theander, T G

AU - Nielsen, M A

N1 - Copyright © 2011 Elsevier Ltd. All rights reserved.

PY - 2012/1/11

Y1 - 2012/1/11

N2 - A vaccine protecting women against placental malaria could be based on the sub-domains of the VAR2CSA antigen, since antibodies against the DBL4e{open}-ID4 subunit of the VAR2CSA protein can inhibit parasite binding to the placental ligand chondroitin sulphate A (CSA). Here we tested the ability of DBL4e{open}-ID4 to induce binding-inhibitory antibodies when formulated with adjuvants approved for human use. We have characterized the immune response of DBL4e{open}-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 DBL4e{open}-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 DBL4e{open}-ID4 antigen. These results demonstrate that the DBL4e{open}-ID4 antigen is highly immunogenic and that binding inhibitory antibodies are induced when formulated with any of the tested adjuvants.

AB - A vaccine protecting women against placental malaria could be based on the sub-domains of the VAR2CSA antigen, since antibodies against the DBL4e{open}-ID4 subunit of the VAR2CSA protein can inhibit parasite binding to the placental ligand chondroitin sulphate A (CSA). Here we tested the ability of DBL4e{open}-ID4 to induce binding-inhibitory antibodies when formulated with adjuvants approved for human use. We have characterized the immune response of DBL4e{open}-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 DBL4e{open}-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 DBL4e{open}-ID4 antigen. These results demonstrate that the DBL4e{open}-ID4 antigen is highly immunogenic and that binding inhibitory antibodies are induced when formulated with any of the tested adjuvants.

U2 - 10.1016/j.vaccine.2011.11.068

DO - 10.1016/j.vaccine.2011.11.068

M3 - Journal article

C2 - 22122859

SN - 0264-410X

VL - 30

SP - 572

EP - 579

JO - Vaccine

JF - Vaccine

IS - 3

ER -