Oral Abstract Session 01 - Global HIV Vaccine Enterprise

POSTERS
Posters
Topic 1: Adjuvants, Immunogens and Inserts
P01.15
Robust Antibody and Cellular Responses with an
Improved DNA Vaccine Alone
N. Hutnick 1 , D.J. Myles 1 , K. Muthumani 1 , M. Morrow 2 , J. Yan 2 ,
A.S. Khan 2 , N.Y. Sardasai 2 , D.B. Weiner 1
1 University of Pennsylvania, Philadelphia, PA, USA; 2 Inovio
Pharmaceuticals, Blue Bell, PA, USA
Background: The recent results of the RV144 trial demonstrate
that HIV-specific antibodies may provide protection from
infection. DNA vaccines may represent an important HIV
vaccine platform since they are safe, relatively inexpensive to
manufacture, and stable at room temperature. However, the
platform has been used largely as a prime modality limited to
induce low level CD4 T cell responses in NHP and humans. In this
study we sought to improve our current DNA vaccines to induce
HIV-specific antibodies with plasmid vaccination alone.
Methods: Groups of 5 Indian Rhesus Macaques were vaccinated
with pHIV consensus gag, pol, and clade C envelopes delivered IM
with in-vivo electroporation at weeks 0, 4 and 12. Immunogenicity
was measured two weeks after each dose.
Results: Three doses of an HIV DNA vaccine alone induced
robust cellular and antibody responses. Despite using clade C
based enveloped, high binding titers were detectable against
gp120s from multiple clades. Neutralizing titers were in the
100’s range to a panel of clade B and C tier 1 viruses. These
data establish that designed DNA envelop antigens can drive
functional immunity in NHP.
Conclusion: Multiple improvements to DNA vaccine technology
have significantly enhanced the immunogenicity of the platform.
Just three doses of a plasmid based HIV vaccine induced robust
binding and neutralizing antibodies as well as effector T-cell
responses in NHP. We are currently expanding the immunity
induced by these constructs through novel DNA adjuvants as
well as in prime-boost combinations.
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AIDS Vaccine 2012
P01.16
Adjuvant-Dependent Cytokine Profiles in the Context
of a DNA Prime-Protein Boost HIV-1 Vaccine
R. Buglione-Corbett 1 , K. Pouliot 1 , R. Marty-Roix 1 , K. West 1 ,
S. Wang 1 , E. Lien 1 , S. Lu 1
1University of Massachusetts Medical School, Worcester, MA,
USA
Background: Heterologous prime-boost vaccinations have
emerged as a promising strategy to generate protective
immunity against a variety of pathogens. Our previous clinical
work has demonstrated that an HIV-1 gp120 DNA prime-protein
boost vaccine, DP6-001, elicits enhanced neutralizing antibody
responses as well as cell-mediated immune responses in humans.
However, the roles of adjuvants remain largely unknown in the
context of such combination vaccines.
Methods: In a mouse model, we studied the effects of adjuvants
QS-21, Alum, and MPL, in the context of DP6-001. Both gp120specific
antibody and T cell responses were monitored by
ELISA and intracellular cytokine staining (ICS), respectively.
Innate cytokine profiles were determined in sera collected 6
hours post-immunization by Cytometric Bead Array (CBA) and
Luminex assays.
Results: Serum anti-Env IgG titers were comparable between
adjuvant groups. All immunized animals demonstrated
comparable positive gp120-specific CD4+ and CD8+ T cell
responses by ICS. Adjuvant profiles were largely determined
by sera cytokines following protein boosting. QS-21 was
distinguished by elevated IL-4, IFNγ, MIP-1β, and IL-1β. MPL was
characterized by elevated G-CSF, KC, and RANTES. Both adjuvant
groups demonstrated elevated IL-6. Production of these sera
cytokine profiles required DNA priming.
Conclusion: Our data indicated that different adjuvants
generate unique patterns of biomarkers, indicating that
different mechanisms are involved in their action. Our results
also provided useful guidance in the selection of an adjuvant
for inclusion in future prime-boost strategies, with the goal of
enhancing immunogenicity while minimizing reactogenicity.