Ching, LK

Stamatatos, L

English

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LK Ching

L Stamatatos

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BioMed Central
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Retrovirology
Open AccessPoster presentation
P19-06. The first hypervariable loop and HIV-1 neutralizing 
antibodies elicited by gp140 env immunogens
LK Ching*1 and L Stamatatos2
Address: 1Pathobiology, University of Washington, Seattle, WA, USA and 2SBRI, Seattle, WA, USA
* Corresponding author    
Background
Efforts to elicit neutralizing antibodies (Nabs) against HIV
have focused on engineering Env immunogens that
mimic the trimeric Env structure on infectious virions
(soluble gp140s). A significant fraction of the antibodies
elicited by Env-derived gp140 immunogens target the first
hypervariable region (V1 loop), suggesting the V1 loop is
immunogenic on these constructs. However, due to
sequence variability, anti-V1 antibodies elicited by gp140s
are not cross-neutralizing.
Methods
To improve our understanding of V1 loop immunogenic-
ity and the way in which the V1 loop may be affecting the
immunogenicity of other Env regions, we: (1)Constructed
an SF162 Env immunogen lacking the V1 loop and exam-
ined how its elimination altered the immunogenic prop-
erties of other epitopes. (2)Used SF162 Env as a scaffold
to express diverse heterologous V1 loops (from YU2, JRFL,
89.6 and HxB2) and then tested these individually or in
combination. The potency, breadth, and epitope specifici-
ties of Abs elicited by the constructs were analyzed and
compared to responses elicited by the wt-SF162 construct.
Results
Our current results indicate that deletion of the V1 loop
does not lead to enhanced cross-reactive neutralizing
responses but enhances the contribution of anti-V3 anti-
bodies to neutralization. Immunizations with the V1 chi-
meric constructs did not elicit antibodies to the
heterologous V1 loops, suggesting that these loops,
although immunogenic on the autologous Env backbone,
are immunosilent on the SF162 Env backbone. The heter-
ologous HxB2 virus was neutralized by antibodies elicited
by all scaffold immunogens and this neutralization is not
mediated by V1- or V3-directed antibodies.
Conclusion
V1 dampening by deletion does not lead to more cross-
reactive neutralizing responses but does alter the immu-
nogenicity of regions outside the V1 loop, such as the V3
loop. Expressing heterologous V1 loops on a given Env
background dampens the immunogenicity of the V1 loop
but does not result in the elicitation of cross-reactive
NAbs.
from AIDS Vaccine 2009
Paris, France. 19–22 October 2009
Published: 22 October 2009
Retrovirology 2009, 6(Suppl 3):P326 doi:10.1186/1742-4690-6-S3-P326
<supplement> <title> <p>AIDS Vaccine 2009</p> </title> <editor>Anna Laura Ross</editor> <note>Meeting abstracts – A single PDF containing all abstracts in this Supplement is available <a href="http://www.biomedcentral.com/content/files/pdf/1742-4690-6-S3-full.pdf">here</a>.</note> <url>http://www.biomedcentral.com/content/pdf/1471-2105-10-S12-info.pdf</url> </supplement>
This abstract is available from: http://www.retrovirology.com/content/6/S3/P326
© 2009 Ching and Stamatatos; licensee BioMed Central Ltd. 


P19-06. The first hypervariable loop and HIV-1 neutralizing antibodies elicited by gp140 env immunogens

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P19-06. The first hypervariable loop and HIV-1 neutralizing antibodies elicited by gp140 env immunogens

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