Oral Abstract Session 01 - Global HIV Vaccine Enterprise

Topic 12: Vaccine Concepts and Design
P12.61 LB
Design And Development of a New Lentiviral Based
Anti-HIV Therapeutic Vaccine
M. Rodriguez 1 , E. Sarry 1 , A. Bejanariu 1 , L. Casaban 1 , S. Abdalla 1 ,
E. Sabbah-Petrover 1 , C. Bauche 1
1 Theravectys, Paris, France
Background: Theravectys develops a new generation of
prophylactic and therapeutic vaccines using optimized lentiviral
vectors. It’s most advanced product, a therapeutic anti-HIV
vaccinal treatment, will enter clinical Phase I/II within a few
weeks. This vaccination will allow seropositive patients to gain
an immunological status identical to the so-called “Functional
Cured” patients who develop an efficient immunological
response capable of controlling the infection without therapy
Methods: Vaccine candidates are integrative and selfinactivated
live-recombinant lentiviral vectors. They encode an
HIV antigen, under the regulation of a patented promoter that
is preferentially induced in APC (generating of a strong, specific
and long lasting T-cell immune response), and showing a basal
level expression in all cells (allowing their elimination by the
settled immune response).
Furthermore, Theravectys developed a vaccination regimen
based on iterative immunizations with lentivectors encoding the
same HIV transgene, relying on different VSV-G serotypes for
pseudotyping without generating cross-neutralizing antibodies.
These candidates were classified as “Live recombinant vectored
vaccines” (EMA, 2011)
Results: Theravectys set up an innovative manufacturing process
combining high production yields, impurity profiles compatible
with direct injections into humans and high immunogenicity.
Pilot and GMP batches have been manufactured and GLP
preclinical studies (amongst which biodistribution, shedding and
toxicity) performed, that showed the restricted diffusion of the
vaccine candidates after injection and their fast disappearance
within few weeks, correlated with an absence of macroscopic
and microscopic toxicity
Conclusion: These data allowed the settlement of an anti-
HIV therapeutic Phase I/II clinical trial that should receive the
authorization of the French regulatory agency before the end
of July.
This trial will be held in France and Belgium and plans the
enrollment of 36 HIV-1 infected patients. Theravectys’ anti-HIV
vaccine treatment will be assessed at three doses and safety,
tolerability and immunogenicity compared to a placebo group.
Results are expected by September 2014 with intermediary
analyses in September 2013
P12.62 LB
AIDS Vaccine 2012
Posters
CN54gp140: Product Characteristics, Preclinical and
Clinical Use - Recombinant Glycoprotein for HIV
Immunization
D. Katinger 1 , S. Jeffs 2 , F. Altmann 3 , A. Cope 2 , P. McKay 2 ,
N. Almond 4 , E. Sandström 5 , B. Hejdeman 5 , G. Biberfeld 5 ,
C. Nilsson 6 , D. Hallengärd 5 , B. Wahren 5 , T. Lehner 7 , M. Singh 8 ,
D.J. Lewis 9 , C. Lacey 10 , R. Shattock 2
1 Polymun Scientific GmbH, Klosterneuburg, Austria; 2 Imperial
College, London, United Kingdom (Great Britain); 3 Universität
für Bodenkultur, Vienna, Austria; 4 HPA-NIBSC, Potters Bar,
United Kingdom (Great Britain); 5 Karolinska Institutet,
Stockholm, Sweden; 6 Swedish Institute for Communicable
Disease Control, Solna, Sweden; 7 King’s College London at
Guy’s Hospital, London, United Kingdom (Great Britain);
8 Lionex Diagnostics & Therapeutics GmbH, Braunschweig,
Germany; 9 University of Surry, Guildford, United Kingdom
(Great Britain); 10 University of York, York, United Kingdom
(Great Britain)
Background: The usefulness of HIV envelope proteins for vaccine
design is widely accepted since the RV144 HIV-1 prime-boost
vaccine trial. It is assumed that a trimeric structure close to the
natural form of the HIV envelope is preferable.
Methods: We have expressed the soluble form of the HIV
envelope of the C/B’ strain 97/CN/54 in CHO cells. The production
process consisted of a large-scale fed-batch fermentation,
an antibody-based affinity chromatography plus additional
purifying steps. CN54gp140 was extensively characterized for
purity and identity. All glycosylation sites were characterized by
mass spectrometry. Immunogenicity and safety were evaluated
in mice, rabbits, mini-pigs, sheep as well as non-human primates.
The antigen was formulated for clinical phase I studies in Tris
buffer (MUCOVAC I, HIVIS07) in HEC gel (MUCOVAC I) as well as
chemically conjugated to hsp70 (MUVAPRED).
Results: The vaccine antigen candidate CN54gp140 proved to
be of high purity and long-term stability. The immune response
was strongest with i.m. application whereas the mucosal routes
(i.vag., i.n.) were less immunogenic. Safety was demonstrated in
animal models as well as in the clinical phase I studies MUCOVAC
I, MUVAPRED and HIVIS07.
Conclusion: CN54gp140 is a highly immunogenic trimeric
envelope protein which can be manufactured in sufficient quality
and quantity for clinical application. It proved to be immunogenic
in several animal models. Finally, it is well tolerated in several
formulations and combinations in humans.
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POSTERS