Phase I Safety and Immunogenicity of Electroporated HIV DNA with or Without Interleukin 12 in Healthy HIVSeronegative African Volunteers
Abstract
Background: DNA vaccines have typically been safe in clinical
trials, but weakly immunogenic. Strategies to enhance their immunogenicity
include i) co-administration of adjuvants and ii)
intramuscular administration by in vivo electroporation (IM/EP).
Methods: Seventy five HIV-uninfected healthy adults were
enrolled into a randomized, double blind, placebo controlled
trial. Multi-antigenic HIV plasmid DNA (HIVMAG) vaccine encoding
clade B gag-pol, env, nef-tat-vif(3 mg/dose), alone or
A-62 POSTER ABSTRACTS
co-administered with pDNA IL12 given IM/EP using TriGridTM
Delivery System, and recombinant Ad35 vaccine containing HIV-
1 subtype A gag, RT, int, nef and gp140 env genes (Ad35-GRIN/
ENV; 2 · 1010 vp) given IM were tested in different prime-boost
regimens (M0,1,2 +M6 or M0+ M4). Group 1: HIVMAG (x3)-
Ad35 (x1), Group 2: HIVMAG+ 100 ug IL12 (x3)- Ad35 (x1),
Group 3: HIVMAG+ 1000 ug IL12 (x3)- Ad35(x1), Group 4:
HIVMAG+ 1000 ug IL12 (x1)- Ad35 (x1), Group 5: Ad35 (x1)-
HIVMAG+ 1000 ug IL12 (x1). All IM/EP vaccinations required
bilateral administrations, one into each deltoid. Safety, tolerability
and immunogenicity were assessed at predetermined time
points.
Results: Both vaccines were safe and well-tolerated. All but one
local and all systemic reactogenicity events were mild or moderate
in severity. No SAEs were reported. Preliminary group unblinded
IFNy ELISPOT results show that 2 weeks post 3 rdDNA
prime the proportions of volunteers in Groups 1–3 responding
to any peptide were 82, 64 and 42% and 2 weeks post Ad35
boost73, 82 and 89%, with corresponding increases in magnitude
post boost. Response rates in Groups 4 and 5 were 50% and
46%, respectively, after last (second) vaccination. An average of
4 out of 12 peptide pools per vaccinee was recognized; further
studies to assess epitope breadth and polyfunctionality are in
progress.
Conclusion: Repeated administration of HIV MAG + / - IL12 by
IM/EP was acceptable among African volunteers. Preliminary
ELISPOT data showed that HIVMAG by IM/EP was immunogenic
but currently there is no clear indication that pDNA IL12
enhanced the immune responses.
Citation
Anzala,O.,2013.Phase I Safety and Immunogenicity of Electroporated HIV DNA with or Without Interleukin 12 in Healthy HIVSeronegative African Volunteers.Publisher
University of Nairobi
Collections
- Faculty of Health Sciences (FHS) [10385]