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

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

JOURNAL=Frontiers in Immunology

VOLUME=8

YEAR=2017

URL=https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2017.01654

DOI=10.3389/fimmu.2017.01654

ISSN=1664-3224

ABSTRACT=<p>Well-ordered soluble HIV-1 envelope glycoprotein (Env) spike mimetics such as Native Flexibly Linked (NFL) trimers display high homogeneity, desired antigenicity, and high <italic>in vitro</italic> 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.</p>