Glutaraldehyde Cross-linking of HIV-1 Env Trimers Skews the Antibody Subclass Response in Mice.
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.
['Soldemo|Martina|M|', 'Àdori|Monika|M|', 'Stark|Julian M|JM|', 'Feng|Yu|Y|', 'Tran|Karen|K|', 'Wilson|Richard|R|', 'Yang|Lifei|L|', 'Guenaga|Javier|J|', 'Wyatt|Richard T|RT|', 'Karlsson Hedestam|Gunilla B|GB|']
cross-linking HIV-1 env mice immunogenicity antibody isotypes gluteraldehyde vaccine responses