B Liu

DF Smith

H Fu

H Zhang

RJ Luallen

RW Doms

Y Geng

PubMed

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POSTER PRESENTATION Open Access
2G12/PGT-binding yeast glycoprotein Gp38 elicits
mannose-specific HIV-1 Env cross-reactive
antibodies
H Zhang1*, H Fu1, B Liu1, RJ Luallen1, RW Doms2, DF Smith3, Y Geng1
From AIDS Vaccine 2012
Boston, MA, USA. 9-12 September 2012
Background
The increasing numbers of broad neutralizing antibodies
(bNAbs) that target carbohydrates of HIV envelops
highlight the importance of designing immunogens to
elicit such types of bNAbs for an effective HIV vaccine.
Methods
PGT bNAbs-cross reactive proteins were detected by
Western blots and identified by nano-LC-MS/MS. Rabbit
antisera were raised with single PGT bNAbs-reactive yeast
glycoprotein, and tested by ELISA, Western blots and gly-
can microarray. HIV-1 pseudoviruses were generated in
293T cells, and neutralization assay was performed using
TZM-bl cells.
Results
Using the newly identified, glycan-specific PGT bNAbs to
search for their binders from a triple mutant(TM) strain
of Saccharomyces cerevisiae, we found that the PGT
bNAbs not only bind to the previously identified 2G12-
reactive glycoproteins but also recognize several
unknown proteins in TM yeast. One of them was identi-
fied as a short version of Gp38 with N-terminus trunca-
tion. Based on immunization of rabbits with various
formulations and strategies, we found that a high titer of
HIV-1 Env cross-reactive antibodies was induced when
using a promiscuous T-cell epitope peptide conjugated
Gp38 in a formulation with a Toll-like receptor 2 agonist
and aluminum salts. The Gp38-elicited antibodies could
bind to a broad range of monomeric gp120s from HIV
and SIV. Moreover, the antibodies could also efficiently
neutralize HIV-1 pseudoviruses when the viruses were
produced in the presence of a mannosidase inhibitor
kifunensine, which enriches high-mannose Man9-
GlcNAc2 N-linked glycans. Glycan microarray analysis
showed that these antibodies bind to the synthetic
Mana1,2-Mana1,2-Man containing oligosaccharides.
Conclusion
These data suggest that yeast glycoprotein Gp38, as well
as its truncated form, is an efficient binder to the glycan-
specific HIV bNAbs, and that Gp38 is able to induce a
strong glycan-specific HIV-reactive antibody response
when incorporated with appropriate adjuvants. These
results encourage us to further explore the strategies to
induce 2G12/PGT-like antibodies using Gp38 as well as
its truncated form.
Author details
1ProSci Inc., Poway, CA, USA. 2University of Pennsylvania, Philadelphia, PA,
USA. 3Emory University , Atlanta, GA, USA.
Published: 13 September 2012
doi:10.1186/1742-4690-9-S2-P357
Cite this article as: Zhang et al.: 2G12/PGT-binding yeast glycoprotein
Gp38 elicits mannose-specific HIV-1 Env cross-reactive antibodies.
Retrovirology 2012 9(Suppl 2):P357.
1ProSci Inc., Poway, CA, USA
Full list of author information is available at the end of the article
Zhang et al. Retrovirology 2012, 9(Suppl 2):P357
http://www.retrovirology.com/content/9/S2/P357
© 2012 Zhang et al; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons
Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in
any medium, provided the original work is properly cited.


2G12/PGT-binding yeast glycoprotein Gp38 elicits mannose-specific HIV-1 Env cross-reactive antibodies

http://dx.doi.org/10.1186/1742-4690-9-S2-P357

2G12/PGT-binding yeast glycoprotein Gp38 elicits mannose-specific HIV-1 Env cross-reactive antibodies

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