Journal
PLOS ONE
Volume 10, Issue 9, Pages -Publisher
PUBLIC LIBRARY SCIENCE
DOI: 10.1371/journal.pone.0135513
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Funding
- Agence Nationale de Recherche pour le Sida et hepatites virales through Vaccine Research Institute programme [CRA 2007-291]
- National Institutes of Health [U-19 AI-57234]
- Baylor Healthcare System through Baylor Research Institute
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Targeting dendritic cell-specific endocytic receptors using monoclonal antibodies fused to desired antigens is an approach widely used in vaccine development to enhance the poor immunogenicity of protein-based vaccines and to induce immune responses. Here, we engineered an anti-human DCIR recombinant antibody, which cross-reacts with the homologous cynomoigous macaque receptor and was fused via the heavy chain C-terminus to HIV Gagp24 protein (alpha DCIR.Gagp24). In vitro, alpha DCIR.Gagp24 expanded multifunctional antigen-specific memory CD4(+) T cells recognizing multiple Gagp24 peptides from HIV-infected patient peripheral blood mononuclear cells. In non human primates, priming with alpha DCIR.Gagp24 without adjuvant elicited a strong anti-Gagp24 antibody response after the second immunization, while in the non-targeted HIV Gagp24 protein control groups the titers were weak. The presence of the double-stranded RNA poly(I:C) adjuvant significantly enhanced the anti-Gagp24 antibody response in all the groups and reduced the discrimination between the different vaccine groups. The avidity of the anti-Gagp24 antibody responses was similar with either alpha DCIR.Gagp24 or Gagp24 immunization, but increased from medium to high avidity in both groups when poly(I: C) was co-administered. This data provides a comparative analysis of DC-targeted and non-targeted proteins for their capacity to induce antigen-specific antibody responses in vivo. This study supports the further development of DCIR-based DC-targeting vaccines for protective durable antibody induction, especially in the absence of adjuvant.
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