Abstract
In vivo antigen targeting to dendritic cells (DCs) has been used as a way to improve immune responses. Targeting is accomplished with the use of monoclonal antibodies (mAbs) to receptors present on the DC surface fused with the antigen of interest. An anti-DEC205 mAb has been successfully used to target antigens to the DEC205+CD8α+ DC subset. The administration of low doses of the hybrid mAb together with DC maturation stimuli is able to activate specific T cells and induce production of high antibody titres for a number of different antigens. However, it is still not known if this approach would work with any fused protein. Here we genetically fused the αDEC205 mAb with two fragments (42-kDa and 19-kDa) derived from the ~200 kDa Plasmodium vivax merozoite surface protein 1 (MSP1), known as MSP142 and MSP119, respectively. The administration of two doses of αDEC-MSP142, but not of αDEC-MSP119 mAb, together with an adjuvant to two mouse strains induced high anti-MSP119 antibody titres that were dependent on CD4+ T cells elicited by peptides present in the MSP133 sequence, indicating that the presence of T cell epitopes in antigens targeted to DEC205+ DCs increases antibody responses.
Highlights
Targeting is accomplished with the use of monoclonal antibodies to receptors present on the DC surface fused with the antigen of interest
Antigen targeting to the CD8α+DC population through the use of αDEC205 hybrid monoclonal antibodies (mAbs) has been successfully used in different models, and was shown to induce both CD8+ and CD4+ T cells[5,6,7,13,15,17,18,19,20,21,22,23,24]
An increase in either anti-MSP119 or anti-MSP133 antibody titres was observed after the administration of the second dose, which has been consistently observed in other models[5,14]
Summary
Targeting is accomplished with the use of monoclonal antibodies (mAbs) to receptors present on the DC surface fused with the antigen of interest. The administration of low doses of the hybrid mAb together with DC maturation stimuli is able to activate specific T cells and induce production of high antibody titres for a number of different antigens It is still not known if this approach would work with any fused protein. The administration of two doses of αDEC-MSP142, but not of αDECMSP119 mAb, together with an adjuvant to two mouse strains induced high anti-MSP119 antibody titres that were dependent on CD4+ T cells elicited by peptides present in the MSP133 sequence, indicating that the presence of T cell epitopes in antigens targeted to DEC205+ DCs increases antibody responses. DCs are able to directly activate B cells to mature and produce high affinity antibodies[2] Because of their central role in the induction of immunity, manipulation of DCs is an interesting strategy to induce adaptive immune responses. These results indicated that all these antigens possessed antigenic epitopes recognized by the immune system
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