Bar, KJ

Decker, J

Hahn, BH

Keele, BF

Kwong, PD

Li, H

McLellan, J

Salazar, M

Salazar-Gonzales, J

Shaw, GM

Wang, S

Yang, Y

English

PubMed

Hahn BH

Yang Y

Wang S

Li H

Salazar M

Salazar-Gonzales J

McLellan J

Decker J

Keele BF

Bar KJ

Kwong PD

Shaw GM

Directory of Open Access Journals

Retrovirology

P04-43. Neutralizing antibody responses against conformational envelope epitopes in early HIV-1 infection

KJ Bar

BF Keele

J Decker

J McLellan

J Salazar-Gonzales

M Salazar

H Li

S Wang

Y Yang

BH Hahn

PD Kwong

GM Shaw

Springer - Publisher Connector

BioMed Central
Page 1 of 1
(page number not for citation purposes)
Retrovirology
Open AccessPoster presentation
P04-43. Neutralizing antibody responses against conformational 
envelope epitopes in early HIV-1 infection
KJ Bar*1, BF Keele2, J Decker1, J McLellan3, J Salazar-Gonzales1, M Salazar1, 
H Li1, S Wang1, Y Yang3, BH Hahn1, PD Kwong3 and GM Shaw1
Address: 1Medicine, University of Alabama at Birmingham, AL, USA, Birmingham, USA, 2National Cancer Institute-Frederick, Frederick, USA and 
3National Institutes of Health, Bethesda, MD, USA
* Corresponding author    
Background
Identification of the transmitted/founder virus in HIV-1
infection allows a unique opportunity to explore the ear-
liest processes of immune pressure and escape. Through
single genome amplification (SGA), we can identify the
transmitted envelope (env), characterize the diversity of
plasma viral quasispecies at subsequent time points, and
characterize neutralizing antibody (Nab) responses.
Methods
SGA of HIV-1 plasma viral RNA from CHAVI subjects 040
(CH040) and 077 (CH077) was performed. The transmit-
ted env and site-directed mutants representing the domi-
nant mutations occurring over the first year of infection
were cloned. Pseudotyped viruses were generated and
neutralization susceptibility to autologous plasma was
tested. Adsorption assays using linear peptides and con-
formationally intact gp120 and gp140 Env monomers
were performed.
Results
In CH040, a single amino acid (AA) mutation arising in
V1 by week 12 post-infection conferred complete escape
from plasma Nab. A two AA mutation at the base of V3
arising at week 24 also conferred escape from week 12 and
week 24 plasma Nab pressure. Neither linear V1 peptides
nor conformationally intact Env monomers were able to
adsorb neutralizing antibody. In CH077, mutations in
both V2 and C2 cause escape from the plasma Nab
response at week 24. Linear V2 peptides were not able to
adsorb away neutralization.
Conclusion
SGA allowed determination of the transmitted virus and
subsequent variants and enabled detailed analysis of early
Nab epitopes and viral escape pathways. In CH040, V1
and V3 mutations each confer total escape from autolo-
gous plasma Nab. This early Nab likely recognizes a con-
formational epitope involving protomer-protomer
interaction since the autologous monomeric gp120
adsorbed b12 Nab activity but not the Nab in CH040
plasma. Similarly, in CH077, we observe that the earliest
Nab likely recognizes a conformational epitope involving
V2 and C2. Elicitation of Nab against conformational
epitopes may be a common theme in early HIV-1 infec-
tion.
from AIDS Vaccine 2009
Paris, France. 19–22 October 2009
Published: 22 October 2009
Retrovirology 2009, 6(Suppl 3):P71 doi:10.1186/1742-4690-6-S3-P71
<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/P71
© 2009 Bar et al; licensee BioMed Central Ltd. 


Crossref

file:///data/core-remote/dit/data/Springer-OA/pdf/3a7/aHR0cDovL2xpbmsuc3ByaW5nZXIuY29tLzEwLjExODYvMTc0Mi00NjkwLTYtUzMtUDcxLnBkZg==.pdf

P04-43. Neutralizing antibody responses against conformational envelope epitopes in early HIV-1 infection

Abstract

Similar works

Full text

Available Versions

Directory of Open Access Journals

Springer - Publisher Connector

Crossref