posted on 2021-10-15, 07:13authored bySachin
S. Shivatare, Ting-Jen Rachel Cheng, Yang-Yu Cheng, Vidya S. Shivatare, Tsung-I Tsai, Hong-Yang Chuang, Chung-Yi Wu, Chi-Huey Wong
While the improved treatment of human
immunodeficiency virus type
1 (HIV-1) infection is available, the development of an effective
and safe prophylactic vaccine against HIV-1 is still an unrealized
goal. Encouragingly, the discovery of broadly neutralizing antibodies
(bNAbs) from HIV-1 positive patients that are capable of neutralizing
a broad spectrum of HIV-1 isolates of various clades has accelerated
the progress of vaccine development in the past few years. Some of
these bNAbs recognize the N-glycans on the viral surface gp120 glycoprotein.
We have been interested in using the glycan epitopes recognized by
bNAbs for the development of vaccines to elicit bNAb-like antibodies
with broadly neutralizing activities. Toward this goal, we have identified
novel hybrid-type structures with subnanomolar avidity toward several
bNAbs including PG16, PGT121, PGT128-3C, 2G12, VRC13, VRC-PG05, VRC26.25,
VRC26.09, PGDM1400, 35O22, and 10-1074. Here, we report the immunogenicity
evaluation of a novel hybrid glycan conjugated to carrier DTCRM197, a nontoxic mutant of the diphtheria toxin, for immunization in
mice. Our results indicated that the IgG response was mainly against
the chitobiose motif with nonspecific binding to a panel of N-glycans
with reducing end GlcNAc–GlcNAc (chitobiose) printed on the
glass slides. However, the IgM response was mainly toward the reducing
end GlcNAc moiety. We further used the glycoconjugates of Man3GlcNAc2, Man5GlcNAc2, and
Man9GlcNAc2 glycans for immunization, and a
similar specificity pattern was observed. These findings suggest that
the immunogenicity of chitobiose may interfere with the outcome of
N-glycan-based vaccines, and modification may be necessary to increase
the immunogenicity of the entire N-glycan epitope.