Oral Abstract Session 01 - Global HIV Vaccine Enterprise

Oral Abstract Session 01: Animal Models
OA01.01
Significant Protection from Infection and AIDS
Progression After Gastrointestinal and Oral
Vaccinations, Respectively, with a SIV DNA/rMVA
Vaccine
A. Aldovini 1 , M. Manrique 1 , A. Cobo-Molinos 1 , P. Kozlowski 2 ,
A. Carvlle 3
1 Children’s Hospital Boston, Harvard Medical School, Boston,
MA, USA; 2 Louisiana State University Health Sciences Center,
New Orleans, LA, USA; 3 New England Primate Research Center,
Harvard Medical School, Southborough, MA, USA
Background: Nasal SIV vaccination can significantly protect
from AIDS progression.
Methods: We compared four mucosal routes of vaccination
in four groups of seven female Rhesus Macaques (RM) each,
immunized in the oral cavity (O), gastrointestinally (GI), nasally
(N) and vaginally (V) with mutated proviral SIV, IL-2 and IL-
15 DNAs and SIV rMVA. Vaccinated and control animals were
challenged vaginally with repeated low-dose of SIVmac251.
Results: Only N vaccination induced a significant increase
in plasma SIV-IgG titers. Significantly higher systemic, rectal
and vaginal SIV-specific T-cell responses were detected in the
oral group during the immunization. The median number of
challenges required to become infected was significantly higher
in the GI group (32; 16 for O, 12 for V, 9 for N, 11 for controls).
Repeated SIV exposure expanded vaginal anti-SIV T-cells in
some of the animals. Seven vaccinated RM (3 in the O, 3 in the
N and 1 in the GI group) suppressed the viremia after the initial
infection peak and maintained it undetectable over the course
of the trial. Immunized, infected animals had significantly lower
levels of systemic T-cell immune activation, better preservation
of CD4+ central memory and α4β7high+ CD4+ T-cells, with
consequent better protection from AIDS. However a lower
protection from AIDS progression was observed in the GI group
compared to the other vaccinated RM, with a median survival
of 24 weeks. A significantly higher loss of CD4+ CM T-cells,
detected early on in this group, correctly predicted its poor
long-term outcome.
Conclusion: Protection from infection in The GI group correlated
with higher anti-SIV CD8+ T cells responses in vaginal T-cells
on the day of first challenge. More than 50% of the O and N
vaccinated RM were still disease-free 72 weeks after infection,
and protection correlated with levels of systemic anti-SIV
IFN-g+/CD8+ T-cells on the day of first challenge.
Oral Abstract Sessions
OA01.02
Antibodies to the Envelope Protein Protect Macaques
from SIVmac251 Acquisition in an Immunization
Regimen That Mimics the RV-144 Thai Trial
G. Franchini 1 , P. Pegu 1 , S. Gordon 1 , B. Keele 2 , M. Doster 1 , Y.
Guan 3 , G. Ferrari 4 , R. Pal 5 , M.G. Ferrari 6 , S. Whitney 7 , L. Hudacik 7 ,
E. Billings 8 , M. Rao 8 , D. Montefiori 9 , D. Venzon 1 , C. Fenizia 1 , J.
Lifson 2 , D. Stablein 2 , J. Tartaglia 10 , N. Michael 11 , J. Kim 11
1 NCI/NIH, Bethesda, MD, USA; 2 NCI-Frederick, Frederick, MD,
USA; 3 Institute of Human Virology Maryland University School of
Medicine, Baltimore, MD, USA; 4 Duke University, Durham, NC,
USA; 5 Advanced Bioscience Laboratories, Rockville, MD, USA;
6 ABL, Rockville, MD, USA; 7 Advanced Biosciences Laboratories,
Rockville, MD, USA; 8 Army Institute of Research, Silver Spring,
MD, USA; 9 Duke University Medical Center, Durham, NC, USA;
10 Sanofi Pasteur Inc, Swifter, PA, USA; 11 Walter Reed Army Intitute
of Research, Silver Spring, MD, USA
Background: The canarypox vector ALVAC-HIV, together with the
HIV gp120 envelope, has protected 31.2% of Thai heterosexual
individuals from HIV acquisition in the RV144 HIV vaccine trial.
This outcome was unexpected, given the limited ability of the
ALVAC-HIV vaccine component to induce CD8+T-cell responses,
and of the HIVgp120 envelope to elicit broad neutralizing
antibodies.
Methods: We vaccinated macaques with an immunization
regimen that mimics the RV144 trial and exposed them to a
mucosal dose of SIV that transmits few virus variants, similar
mac251
to HIV transmission to humans.
Results: Vaccination induced anti-envelope antibodies, modest
CD4+ and CD8+ T-cell responses. One third of the vaccinated
macaques were protected from SIV acquisition, whereas
mac251
the remaining infected vaccinees progressed to disease. Vaccine
induced SIV specific T-and B-cell responses were not different
mac251
in protected or infected animals. The sera of the animals protected
had higher avidity antibodies to the gp120 envelope protein,
recognized the variable envelope region V2, and reduced SIVmac251 infectivity in cells that express high level of α4β7, suggesting a
functional role to antibodies to V2.
Conclusion: The SIV infection macaque faithfully reproduces
mac251
results in humans, and is instrumental in the development of
more efficacious vaccines for HIV.
AIDS Vaccine 2012
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ORAL ABSTRACT SESSIONS