Frontiers in Immunology (Nov 2017)

Glutaraldehyde Cross-linking of HIV-1 Env Trimers Skews the Antibody Subclass Response in Mice

  • Martina Soldemo,
  • Monika Àdori,
  • Julian M. Stark,
  • Yu Feng,
  • Karen Tran,
  • Richard Wilson,
  • Lifei Yang,
  • Javier Guenaga,
  • Richard T. Wyatt,
  • Gunilla B. Karlsson Hedestam

DOI
https://doi.org/10.3389/fimmu.2017.01654
Journal volume & issue
Vol. 8

Abstract

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Well-ordered soluble HIV-1 envelope glycoprotein (Env) spike mimetics such as Native Flexibly Linked (NFL) trimers display high homogeneity, desired antigenicity, and high in vitro stability compared to previous generation soluble HIV-1 Env trimers. Glutaraldehyde (GLA) cross-linking was shown to further increase the thermostability of clade C 16055 NFL trimers and enhance the induction of tier 2 autologous neutralizing antibodies in guinea pigs. Here, we investigated if GLA fixation affected other aspects of the Env-specific immune response by performing a comparative immunogenicity study in C57BL/6 mice with non-fixed and GLA-fixed 16055 NFL trimers administered in AbISCO-100 adjuvant. We detected lower Env-specific binding antibody titers and increased skewing toward Th2 responses in mice immunized with GLA-fixed trimers compared to mice immunized with unfixed trimers, as shown by a higher Env-specific IgG1:IgG2b antibody subclass ratio. These results suggest that the presence of GLA adducts on Env influences the quality of the induced antibody response.

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