Delivering HIV Gagp24 to DCIR Induces Strong Antibody Responses $In\ Vivo$ - CEA - Commissariat à l’énergie atomique et aux énergies alternatives Access content directly
Journal Articles PLoS ONE Year : 2015

Delivering HIV Gagp24 to DCIR Induces Strong Antibody Responses $In\ Vivo$

Abstract

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 cynomolgous macaque receptor and was fused via the heavy chain C-terminus to HIV Gagp24 protein (αDCIR.Gagp24). In vitro, αDCIR.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 αDCIR.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 αDCIR.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.

Dates and versions

cea-01825887 , version 1 (28-06-2018)

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Anne-Laure Flamar, Vanessa Contreras, Sandra Zurawski, Monica Montes, Nathatlie Dereuddre-Bosquet, et al.. Delivering HIV Gagp24 to DCIR Induces Strong Antibody Responses $In\ Vivo$. PLoS ONE, 2015, 10, pp.0135513. ⟨10.1371/journal.pone.0135513⟩. ⟨cea-01825887⟩
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