Background: One of the great challenges for an HIV vaccine is to elicit broadly neutralizing antibodies specific for conserved epitopes from which the virus cannot easily escape. The CD4 binding site is one such epitope against which several antibodies (e.g. b12, VRC01) have been isolated. In macaques infected with SHIV, passive immunization with these CD4-directed neutralizing antibodies fails to control the virus, but prophylactic administration is highly protective. Similarly, patients who generate neutralizing antibodies over the course of an HIV infection derive no clinical benefit from them, but eliciting such antibodies prophylactically by vaccination may prevent the virus from establishing its lethal foothold

Hanson, M.

Irvine, Darrell J.

Kriegsman, Barry A.

Mata-Fink, Jordi

Wittrup, Karl Dane

Retrovirology

PubMed

J Mata-Fink

M Hanson

B Kriegsman

D Irvine

K Wittrup

Crossref

Engineered gp120 immunogens that elicit VRC01-like antibodies by vaccination

Springer - Publisher Connector

POSTER PRESENTATION Open Access
Engineered gp120 immunogens that elicit
VRC01-like antibodies by vaccination
J Mata-Fink*, M Hanson, B Kriegsman, D Irvine, K Wittrup
From AIDS Vaccine 2012
Boston, MA, USA. 9-12 September 2012
Background
One of the great challenges for an HIV vaccine is to elicit
broadly neutralizing antibodies specific for conserved epi-
topes from which the virus cannot easily escape. The
CD4 binding site is one such epitope against which sev-
eral antibodies (e.g. b12, VRC01) have been isolated. In
macaques infected with SHIV, passive immunization
with these CD4-directed neutralizing antibodies fails to
control the virus, but prophylactic administration is
highly protective. Similarly, patients who generate neu-
tralizing antibodies over the course of an HIV infection
derive no clinical benefit from them, but eliciting such
antibodies prophylactically by vaccination may prevent
the virus from establishing its lethal foothold.
Methods
Yeast surface display is a powerful method for rapidly
engineering complex glycoproteins. We have developed a
stripped core gp120 that presents a functional CD4 bind-
ing site when displayed on yeast, and an accompanying
suite of tools with which to map conformational epitopes
of neutralizing antibodies, design novel immunogens, and
monitor the specificity of serum following immunization.
Results
We map the epitopes of the anti-gp120 antibodies
VRC01, b12, and b13, and uncover subtle energetic dif-
ferences in their nearly-overlapping epitopes that are not
obvious from existing crystal structures. With this infor-
mation, we design novel gp120 immunogens that share
the VRC01 epitope but whose other surface amino acids
are highly diverse. When mice are immunized with these
immunogens in a heterologous prime-boost format they
elicit VRC01-competitive antibodies and not the compet-
ing immunodominant specificities seen with a single
immunogen. The antisera are tested for their binding to
a panel of gp120, and their neutralization potential is
assayed.
Conclusion
We have engineered a novel set of immunogens that eli-
cit CD4 binding site-directed antibodies upon immuni-
zation. The yeast display tools may be used to design
future immunogens.
Published: 13 September 2012
doi:10.1186/1742-4690-9-S2-P6
Cite this article as: Mata-Fink et al.: Engineered gp120 immunogens that
elicit VRC01-like antibodies by vaccination. Retrovirology 2012 9(Suppl 2):
P6.
Submit your next manuscript to BioMed Central
and take full advantage of: 
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• Thorough peer review
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Submit your manuscript at 
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Massachusetts Institute of Technology, Cambridge, MA, USA
Mata-Fink et al. Retrovirology 2012, 9(Suppl 2):P6
http://www.retrovirology.com/content/9/S2/P6
© 2012 Mata-Fink 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.


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POSTER PRESENTATION Open AccessEngineered gp120 immunogens that elicitVRC01-like antibodies by vaccinationJ Mata-Fink*, M Hanson, B Kriegsman, D Irvine, K WittrupFrom AIDS Vaccine 2012Boston, MA, USA. 9-12 September 2012BackgroundOne of the great challenges for an HIV vaccine is to elicitbroadly neutralizing antibodies specific for conserved epi-topes from which the virus cannot easily escape. TheCD4 binding site is one such epitope against which sev-eral antibodies (e.g. b12, VRC01) have been isolated. Inmacaques infected with SHIV, passive immunizationwith these CD4-directed neutralizing antibodies fails tocontrol the virus, but prophylactic administration ishighly protective. Similarly, patients who generate neu-tralizing antibodies over the course of an HIV infectionderive no clinical benefit from them, but eliciting suchantibodies prophylactically by vaccination may preventthe virus from establishing its lethal foothold.MethodsYeast surface display is a powerful method for rapidlyengineering complex glycoproteins. We have developed astripped core gp120 that presents a functional CD4 bind-ing site when displayed on yeast, and an accompanyingsuite of tools with which to map conformational epitopesof neutralizing antibodies, design novel immunogens, andmonitor the specificity of serum following immunization.ResultsWe map the epitopes of the anti-gp120 antibodiesVRC01, b12, and b13, and uncover subtle energetic dif-ferences in their nearly-overlapping epitopes that are notobvious from existing crystal structures. With this infor-mation, we design novel gp120 immunogens that sharethe VRC01 epitope but whose other surface amino acidsare highly diverse. When mice are immunized with theseimmunogens in a heterologous prime-boost format theyelicit VRC01-competitive antibodies and not the compet-ing immunodominant specificities seen with a singleimmunogen. The antisera are tested for their binding toa panel of gp120, and their neutralization potential isassayed.ConclusionWe have engineered a novel set of immunogens that eli-cit CD4 binding site-directed antibodies upon immuni-zation. The yeast display tools may be used to designfuture immunogens.Published: 13 September 2012doi:10.1186/1742-4690-9-S2-P6Cite this article as: Mata-Fink et al.: Engineered gp120 immunogens thatelicit VRC01-like antibodies by vaccination. Retrovirology 2012 9(Suppl 2):P6.Submit your next manuscript to BioMed Centraland take full advantage of: • Convenient online submission• Thorough peer review• No space constraints or color figure charges• Immediate publication on acceptance• Inclusion in PubMed, CAS, Scopus and Google Scholar• Research which is freely available for redistributionSubmit your manuscript at www.biomedcentral.com/submitMassachusetts Institute of Technology, Cambridge, MA, USAMata-Fink et al. Retrovirology 2012, 9(Suppl 2):P6http://www.retrovirology.com/content/9/S2/P6© 2012 Mata-Fink et al; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the CreativeCommons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, andreproduction in any medium, provided the original work is properly cited.

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Engineered gp120 immunogens that elicit VRC01-like antibodies by vaccination

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