Ahmed R

Amara RR

Araki K

Basu R

Earl PL

Gangadhara S

Hong J

Iyer S

Kwa S

Lai L

Moss B

Sadagopal S

Villinger F

Wyatt L

S Kwa

S Sadagopal

J Hong

S Gangadhara

R Basu

L Lai

S Iyer

K Araki

PL Earl

L Wyatt

F Villinger

B Moss

R Ahmed

RR Amara

Springer - Publisher Connector

POSTER PRESENTATION Open Access
CD40L adjuvant for DNA/MVA vaccine: enhanced
protection from acquisition of neutralization
sensitive & neutralization resistant mucosal
SIV infections
S Kwa1*, S Sadagopal1, J Hong1, S Gangadhara1, R Basu1, L Lai1, S Iyer1, K Araki1, PL Earl2, L Wyatt2, F Villinger1,
B Moss2, R Ahmed1, RR Amara1
From AIDS Vaccine 2012
Boston, MA, USA. 9-12 September 2012
Background
Generating highly functional antibodies against HIV-1 is
critical to prevent infection. Here we evaluated the ability
of CD40L (a co-stimulatory molecule for B cells and den-
dritic cells) as an adjuvant to prevent mucosal infection
from neutralization-susceptible (SIVE660) and neutraliza-
tion-resistant (SIV251) SIVs.
Methods
Groups of rhesus macaques (10-15 animals/group) were
immunized intramuscularly at 0 and 8 weeks with 3mg of
DNA/SIV or DNA/SIV-CD40L, and boosted with 108 pfu
of MVA/SIV at 16 and 24 weeks. In addition, animals
challenged with SIV251 received 106 pfu of MVA/CD40L
premixed with MVA/SIV immunizations. Both the DNA
and MVA immunogens expressed SIV239 Gag, Pol and
Env. At about 24 weeks after final vaccination, animals
were challenged intrarectally with either SIV251 (8 weekly
doses) or SIVE660 (12 weekly doses) until all unvaccinated
controls became infected.
Results
Adjuvanting DNA with CD40L enhanced (p<0.05) the
titer and avidity of antibodies against SIV239 and
SIVE660 Envs. Adjuvanting both DNA and MVA with
CD40L enhanced (p<0.05) the frequency of B cell follicles
with germinal centers (sites of antibody affinity matura-
tion) in the lymph nodes. Following challenge, animals
vaccinated with CD40L adjuvant showed markedly
enhanced protection from virus acquisition against both
SIVE660 (number of challenges for 50% infection was 2
in controls, 5 in DNA/MVA and 12 in DNA/MVA with
CD40L; p=0.003, 76% vaccine efficacy) and SIV251
(number of challenges for 50% infection was 2 in con-
trols, 2 in DNA/MVA and 6 in DNA/MVA with CD40L;
p=0.04, 55% vaccine efficacy). The enhanced protection
against SIVE660 correlated directly with increased avidity
of anti-SIVE660 Env antibody and correlation analyses
for protection against SIV251 are ongoing. CD40L-adju-
vanted animals also showed 100-fold reduction in peak
virus replication in both infection models.
Conclusion
These results demonstrate that CD40L enhances the
functional quality of anti-Env antibody and protection
from acquisition of neutralization sensitive and resistant
mucosal SIV infections.
Author details
1Emory University, Atlanta, GA, USA. 2NIH, Bethesda, MD, USA.
Published: 13 September 2012
doi:10.1186/1742-4690-9-S2-P365
Cite this article as: Kwa et al.: CD40L adjuvant for DNA/MVA vaccine:
enhanced protection from acquisition of neutralization sensitive &
neutralization resistant mucosal SIV infections. Retrovirology 2012
9(Suppl 2):P365.
1Emory University, Atlanta, GA, USA
Full list of author information is available at the end of the article
Kwa et al. Retrovirology 2012, 9(Suppl 2):P365
http://www.retrovirology.com/content/9/S2/P365
© 2012 Kwa 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.


CD40L adjuvant for DNA/MVA vaccine: enhanced protection from acquisition of neutralization sensitive & neutralization resistant mucosal SIV infections

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CD40L adjuvant for DNA/MVA vaccine: enhanced protection from acquisition of neutralization sensitive &amp; neutralization resistant mucosal SIV infections

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CD40L adjuvant for DNA/MVA vaccine: enhanced protection from acquisition of neutralization sensitive & neutralization resistant mucosal SIV infections

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