Oral Abstract Session 01 - Global HIV Vaccine Enterprise

POSTERS
Posters
Topic 2: Animal Models and Preclinical Trials
P02.11
Mapping of SIVmac T-Cell Epitopes in Cynomolgus
Macaques Immunized with Auxo-GTU-MultiSIV
DNA by the Intradermal Route Followed by
Electroporation
A. Corneau 3 , B. Maciel Da Silva 3 , S. Even 3 , J. Morin 3 , N. Sylla 3 ,
F. Martinon 3 , A. Aarninck 1 , A. Blancher 1 , I. Stanescu 2 ,
R. Le Grand 3 , N. Dereuddre-Bosquet 3
1 Laboratoire D’Immunogénétique Moléculaire EA 3034,
Faculté de Médecine, Toulouse, France; 2 FIT Biotech, Tampere,
Finland; 3 CEA, Fontenay-aux-Roses, France
Background: Intradermal immunization with electroporation
using auxo-GTU-MultiHIV DNA encoding Gag, Nef, Rev and Tat
induces strong and sustained T cell responses in cynomolgus
macaques. Here, we used an equivalent vaccine encoding
SIVmac239 antigens (Gag, Nef, Rev, Tat, Vif, Vpx and Vpr) and we
described the breath of this T cell response.
Methods: Naïve male mauritian cynomolgus macaques were
immunized with auxo-GTU-MultiSIV DNA encoding Gag, Nef, Rev
and Tat (n=14) or by a combination of auxo-GTU-MultiSIV DNA
and auxo-GTU-SIV-vifvprvpx (n=12) by the intradermal route
followed by electroporation. MHC class I and class II haplotypes
were determined by microsatellite analysis. T-cell epitopes were
mapped by IFN-γ ELISPOT in PBMC by using matrix of 15-mer
(overlapping by 11) SIVmac239 Gag, Nef, Rev, Tat, Vif, Vpx and
Vpr peptides. Sequence and length of candidate epitopes were
further optimized.
Results: Immunization induced intense and sustained IFN-γ
ELISPOT responses in peripheral blood. T-cell responses against
MHC class I epitopes were evidenced: two in Gag p15 (KA10(28-
37) presented by Mafa-B*011:01 and EL10(58-68) presented by a
MHC-Ia molecule from haplotype M3), two in Gag p27 (HL9(146-
154) presented by Mafa-B*075:01 and LA9(189-197) presented
by a MHC-Ib from haplotype M1), three in Nef (AS10(4-13)
presented by a MHC-Ib molecule from haplotype M3; RM9(103-
111) presented by Mafa-A1*063:02; LD10(146-155) presented
by a MHC-Ia from haplotype M1M2M3), one in Rev (SP10(59-68)
presented by Mafa-B*075:01), one in Tat (CF9(59-67) presented
by Mafa-A1*063:02), four in Vif and two in Vpx. One MHC class
II epitope was identified in Gag p27 (haplotype M3). Among
these, to our knowledge, AF11 is a newly described epitope in
cynomolgus macaques.
Conclusion: Auxo-GTU-MultiSIV DNA vaccination followed
by electroporation induced multi-epitopic T cell responses,
essentially CD8+ but also CD4+. Determination of SIV T-cell
epitopes in cynomolgus macaques facilitates the monitoring of
specific immune responses and pre-clinical vaccine development
in this model.
112
AIDS Vaccine 2012
P02.12
Development of a HIV-1 Vaccine Using an Orally-
Administered, Replication-Competent Adenovirus
Serotype 4 Vector Expressing Env Clade C Glycoprotein
J. Alexander 1 , M. Gurwith 1 , J. Mendy 1 , L. Vang 1 , D. Manayani 1 ,
J. Avanzini 1 , B. Guenther 1 , P. Farness 1 , B.F. Haynes 2 , H. Liao 2 ,
D.C. Montefiori 3 , C.C. LaBranche 3 , T. Mayall 1
1 PaxVax, San Diego, CA, USA; 2 Duke Human Vaccine Institute,
Duke University School of Medicine, Durham, NC, USA;
3 Department of Surgery, Duke University Medical Center,
Durham, NC, USA
Background: Our hypothesis is that the replicating Ad4 vector
approach, may be the best strategy for an effective HIV-1
vaccine due to advantages of demonstrated clinical safety and
immunogenicity of both the Ad4 backbone and an Ad4 H5N1
vector influenza vaccine evaluated in Phase 1. Unlike other
vectors, it can be bioengineered to express full-length HIV-1
Env gp160. More than 50% of global HIV-1 infections are caused
by clade C viruses and therefore we initiated development of
Ad4-Env160 vaccine using an Env clade C sequence obtained
from CHAVI.
Methods: The Ad4-Env viruses were evaluated for: 1) genetic
stability; 2) Env protein expression by Western blot analysis; 3)
cell-surface Env recognition by broadly neutralizing antibody
(bnAb); and 4) immunogenicity in rabbits.
Results: Genetically stable Ad4 recombinant viruses were
generated which expressed the Env gp120, gp140, and gp160
proteins. A549 cells infected with Ad4-Env160 virus expressed
cell-surface Env that was recognized by bnAb specific for MPER,
CD4bs, V2-V3 loop sequences. Following immunization of rabbits,
Env-specific binding antibodies were induced as measured by
ELISA; 160>140>120.
Conclusion: An Ad4 virus expressing full-length Env160 was
generated and evaluated for genetic stability, protein expression,
recognition by bnAb and immunogenicity. These results
represent substantial progress towards defining a replicating
Ad4 vector, recombinant protein vaccine prime/boost approach
for HIV-1 that could eventually undergo clinical testing. Funding:
NIH/NIAID SBIR 1R43AI091546-01; NIH/NIAID Contract No.
HHSN266200400045C.