Banchereau, J

Cobb, A

Flamar, A

King, B

Levy, Y

Loof, N

Montes, M

Plants, J

Sloan, L

Zurawski, G

Zurawski, S

Retrovirology

English

PubMed

N Loof

M Montes

A Flamar

G Zurawski

A Cobb

J Plants

B King

S Zurawski

L Sloan

Y Levy

J Banchereau

Crossref

BioMed Central
Page 1 of 1
(page number not for citation purposes)
Retrovirology
Open AccessOral presentation
S04-04 OA. HIV-specific responses induced by anti-CD40 targeting 
antibodies
N Loof*1, M Montes1, A Flamar1, G Zurawski1, A Cobb1, J Plants1, B King1, 
S Zurawski1, L Sloan1, Y Levy2 and J Banchereau1
Address: 1HIV Vaccine, INSERM U899-BIIR/INSERM/ANRS Center for Human Vaccines, Dallas, TX, USA and 2INSERM U841, Créteil, France
* Corresponding author    
Background
Antibodies directed against antigen-presenting cell (APC)
receptors can deliver antigens very efficiently. This recep-
tor-targeting vaccine system facilitates the uptake, process-
ing and presentation of extracellular antigens. In our
approach, an antibody against human CD40 was fused to
HIV antigens and these prototype vaccines were tested for
their capacity to stimulate the expansion of HIV-specific
memory T cells.
Methods
Recombinant anti-CD40 antibodies fused to HIV Gag
and/or Nef proteins were tested for their capacity to bind
to DCs and to stimulate expansion of HIV-specific T cells.
PBMC and dendritic cells (DC) from HIV-infected
patients were incubated with Gag-targeting molecules fol-
lowed by anti-Gag PE secondary antibody. Binding on in
CD19+, CD14+ and CD11c+ cells was measured by flow
cytometry. Short-term PBMC cultures (10 days) stimu-
lated with DC-targeting vaccines in the presence of IL-2
were re-stimulated with overlapping peptides covering the
total sequences of Gag and Nef, followed by multiplex
cytokine (Luminex) analysis of supernatants and intracel-
lular staining.
Results
The anti-CD40-HIV-Gag/Nef antibodies bind to B cells,
monocytes and DC with a affinity similar to the parental
anti-CD40 antibody. The HIV antigen-targeting vaccines
displayed a high stimulation capacity in vitro compared
with isotype control (IgG4) fusion proteins, inducing
CD4+ and CD8+ T cell responses against Gag and Nef
peptides even at very low concentrations (0.01 nM).
Moreover, we observed not only antigen-specific secretion
of the Th1/CTL set of cytokines but also of cytokines char-
acteristic of Th2 and IL-21 subsets. The breadth and the
quality of the T cell responses observed in PBMC cultures
matched responses those observed in DC-T cell co-cul-
tures.
Conclusion
Thus CD40 is an excellent candidate for HIV vaccines
based on DC targeting, as it's activation not only causes
maturation of APC but permits efficient presentation and
cross-presentation of HIV epitopes, thereby stimulating
strong recall T cell responses.
from AIDS Vaccine 2009
Paris, France. 19–22 October 2009
Published: 22 October 2009
Retrovirology 2009, 6(Suppl 3):O46 doi:10.1186/1742-4690-6-S3-O46
<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/O46
© 2009 Loof et al; licensee BioMed Central Ltd. 


S04-04 OA. HIV-specific responses induced by anti-CD40 targeting antibodies

Loof, Nicolas

Montes, Monica

Flamar, Anne-Laure

Zurawski, Gérard

Cobb, Amanda

King, Bryan

Zurawski, Sandra

Sloan, Louis

Levy, Yves

Banchereau, Jacques

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https://inserm.hal.science/inserm-00663584v1/file/1742-4690-6-S3-O46.pdf

S04-04 OA. HIV-specific responses induced by anti-CD40 targeting antibodies

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