4.7 Article

The presence of T cell epitopes is important for induction of antibody responses against antigens directed to DEC205+ dendritic cells

Journal

SCIENTIFIC REPORTS
Volume 6, Issue -, Pages -

Publisher

NATURE PUBLISHING GROUP
DOI: 10.1038/srep39250

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Funding

  1. Sao Paulo Research Foundation (FAPESP) [2007/08648-9, 2013/11442-4]
  2. Brazilian National Research Council (CNPq)/National Institutes of Science and Technology in Vaccines (INCTV) [15203*12]
  3. BNP-Paribas Bank
  4. CNPq

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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(+) CD8 alpha(+) 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 alpha DEC205 mAb with two fragments (42-kDa and 19-kDa) derived from the similar to 200 kDa Plasmodium vivax merozoite surface protein 1 (MSP1), known as MSP1(42) and MSP1(19), respectively. The administration of two doses of alpha DEC-MSP1(42), but not of alpha DEC-MSP1(19) mAb, together with an adjuvant to two mouse strains induced high anti-MSP1(19) antibody titres that were dependent on CD4(+) T cells elicited by peptides present in the MSP1(33) sequence, indicating that the presence of T cell epitopes in antigens targeted to DEC205(+) DCs increases antibody responses.

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