Oral Abstract Session 01 - Global HIV Vaccine Enterprise

POSTERS
Posters
Topic 12: Vaccine Concepts and Design
P12.19
Immunisation with the Membrane Proximal
External Region of gp41 of HIV-1 Grafted into
the Transmembrane Envelope Protein of a
Gammaretrovirus
N. Strasz 1 , V. Morozov 1 , J. Kreutzberger 1 , M. Lau 1 , J. Denner 1
1 Robert Koch Institute, Berlin, Germany
Background: Immunisation with the transmembrane envelope
(TM) proteins p15E of different gammaretroviruses (e.g., porcine
endogenous retrovirus, feline leukaemia virus, Koala retrovirus)
resulted in strong neutralising activity, the antibodies recognised
epitopes in the fusion peptide proximal region (FPPR) and in
the membrane proximal external region (MPER). The MPER
epitopes were localised similarly as the epitopes recognised by
the broadly neutralising antibodies 2F5 and 4E10 in gp41 of HIV-
1. Despite the evolutionary difference between HIV-1 and the
gammaretroviruses, the MPER epitope of antibodies neutralising
PERV (FEGWFN) showed partial homology to the epitope of the
4E10 (NWFNIT, note three identical amino acids). To generate
hybrid antigens able to induce 2F5/4E10-like antibodies,
sequences of the MPER and FPPR of gp41 were grafted into the
p15E backbone of a gammaretrovirus.
Methods: Different hybrid antigens were cloned, expressed in E.
coli and purified. Immunisation studies in rats and guinea pigs
were performed and the antisera were characterised by ELISA,
Western blot analysis, epitope mapping using microarray chips
with overlapping peptides and a neutralisation assay based on
TZM-bl cells.
Results: Antibodies against gp41 of HIV-1 were induced,
recognising epitopes in the FPPR, but also the 2F5 epitope
(ELDKWA) in the MPER. Step by step changes in the sequence
of the hybrids resulted in improved binding of the antibodies to
this epitope. However, none of the immune sera or purified IgG
neutralised HIV-1 more that 50%.
Conclusion: Since modifications in the hybrid proteins led to an
increased anti-MPER response, it may be expected that further
modifications increase neutralisation efficacy and that these
hybrids may be the basis for candidate vaccines against HIV-1.
Performed in the frame of the EuroNeut-41 project in the
Seventh Framework Program.
250
AIDS Vaccine 2012
P12.20
Development of a Novel Simian Adenovirus 24 Based
Vaccine Vector
P. Abbink 1 , R.R. Bradley 1 , F. Ball 1 , D. Ng’ang’a 1 , E. Borducchi 1 ,
D.H. Barouch 1
1 Beth Israel Deaconess Medical Center, Boston, MA, USA
Background: Human adenovirus serotype 5 is a potent vaccine
vector, but its use has been hampered by high seroprevalence
amongst people in sub-Sahara Africa. Novel adenoviral vaccine
vectors from strains with lower seroprevalence worldwide are
being developed that can evade pre-existing immunity. Here
we describe the development of a simian Ad24 (sAd24)-based
vaccine vector.
Methods: Neutralizing antibodies against sAd24 were
determined using a panel of 106 rhesus macaque sera and 128
human sera from Rwanda and South Africa using a luciferasebased
adenovirus neutralization assay.
The immunogenicity of a single dose of 10E7, 10E8 or 10E9
virus particles of sAd24-SIV Gag based vector was determined
in C57BL/6 mice. SIV-Gag-specific immune responses were
assessed by Db/AL11 tetramer binding assays, IFN-γ ELISPOT
assays and ICS assays.
Results: Neutralizing antibodies were found in 7% of monkeys,
all with titers 1000. Gag specific cellular immune responses elicited by sAd24-
SIV Gag in mice are comparable to those seen with the human
Ad26 and Ad28 vectors currently in development.
Conclusion: These data suggest that sAd24 is promising for
further studies as a candidate vaccine vector.