B Richardson

DC Malherbe

I Srivastava

L Misher

L Stamatatos

N Doria-Rose

NL Haigwood

S Barnett

T Beckett

W Blay-Puryear

Retrovirology

Crossref

BioMed Central
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Retrovirology
Open AccessPoster presentation
P05-10. Sequential immunization with a subtype B HIV-1 envelope 
quasispecies elicits broader neutralization than vaccination with a 
single envelope clone
DC Malherbe*1, N Doria-Rose2, L Misher3, T Beckett3, W Blay-Puryear4, 
S Barnett5, I Srivastava5, B Richardson6, L Stamatatos7 and NL Haigwood1
Address: 1Oregon Health and Science University, Beaverton, OR, USA, 2National Institute of Health, Bethesda, MD, USA, 3Trubion 
Pharmaceuticals, Seattle, WA, USA, 4Boston University, Boston, MA, USA, 5Novartis Vaccines and Diagnostics, Cambridge, MA, USA, 6University 
of Washington, Seattle, WA, USA and 7Seattle Biomedical Research Institute, Seattle, WA, USA
* Corresponding author    
Background
HIV-1 evolves rapidly within the host, resulting in the
development of diverse HIV-1 variants called a viral ''qua-
sispecies'' population. Envelope (Env) is the only target of
neutralizing antibodies (NAbs), which can prevent infec-
tion of target cells. NAbs develop over time as the Enve-
lope diverges. A major goal of HIV-1 vaccine efforts, so far
elusive, is the design of Env-based immunogens effective
at eliciting broad NAbs. We hypothesized that program-
ming the B cell response could be achieved by exposing
the host to a collection of env variants representing the
viral quasispecies members.
Methods
Fifteen sequences were selected as representatives of the
Env quasispecies in a macaque that developed broad
NAbs following infection with SHIVSF162P4. The exact
sequences were created by site-directed mutagenesis in a
codon-optimized expression plasmid. Rabbits were
immunized via gp160 DNA prime (gene gun) and gp140
protein boost. Three vaccine strategies were compared:
sequential env clones (Sequential), cocktail of env clones
(Mixture), or single env variant (Clonal). Purified IgG was
tested for binding and neutralizing antibodies.
Results
All strategies induced similar levels of Env-specific bind-
ing antibodies regardless of vaccine approach. All groups
developed autologous NAbs, with better neutralization
obtained in the clonal and sequential groups and with
weaker responses to variants with increased number of
potential N-glycosylation sites. The NAb response was
partially directed against the V3 loop. Heterologous neu-
tralization was observed in the sequential group.
Conclusion
This study is the first to explore the use of multiple native
HIV-1 Env variants as immunogens. Immunization with a
collection of env quasispecies variants resulted in the
development of broader NAbs than immunization with a
single env gene alone, suggesting that it is possible to edu-
cate the immune system by exposing it to a native HIV-1
quasispecies derived from an individual with a broadened
NAb response.
from AIDS Vaccine 2009
Paris, France. 19–22 October 2009
Published: 22 October 2009
Retrovirology 2009, 6(Suppl 3):P86 doi:10.1186/1742-4690-6-S3-P86
<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/P86
© 2009 Malherbe et al; licensee BioMed Central Ltd. 


P05-10. Sequential immunization with a subtype B HIV-1 envelope quasispecies elicits broader neutralization than vaccination with a single envelope clone

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P05-10. Sequential immunization with a subtype B HIV-1 envelope quasispecies elicits broader neutralization than vaccination with a single envelope clone

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