Oral Abstract Session 01 - Global HIV Vaccine Enterprise

POSTERS
Posters
Topic 12: Vaccine Concepts and Design
P12.51
Co-immunization with HIV Env DNA and Protein Elicit
Long-Lasting Strong Cellular and Humoral Immune
Responses
J. Li 1 , A. Valentin 1 , V. Kulkarni 1 , C. Alicea 1 , R. Kelly Beach 1 ,
M. Rosati 1 , R. Jalah 1 , S. Reed 2 , B.K. Felber 1 , G.N. Pavlakis 1
1 Frederick National Laboratory for Cancer Research, Frederick,
MD, USA; 2 Infectious Disease Research Institute, Seattle, WA,
USA
Background: We have previously reported that potent, longlasting
HIV-1 Env-specific cell-mediated immune responses could
be elicited in rhesus macaques and mice using plasmids encoding
env DNA as the immunogen. Subsequent experiments showed
that combination of DNA and protein in the form of inactivated
virus particles provided significant protection from infection and
high viremia. We examine a vaccine platform combining DNA and
recombinant Env protein co-immunization at the same time to
generate both strong cellular and humoral immune responses.
Methods: Mice or macaques were immunized with HIV env
gp120 DNA vaccine and/or purified gp120 protein from clade
B or clade C isolates. Mice were immunized twice at 4 weeks
interval with DNA only, protein only formulated in EM005
adjuvant, or DNA&protein/EM005. Macaques were immunized
twice at 4 weeks interval with DNA only, DNA&protein,
DNA&protein/EM005.
Results: DNA&protein co-immunization enhances the Ab
responses compared with DNA or protein only in mice.
DNA&protein co-immunization generated similar levels of
cellular immune responses compared to mice immunized
with DNA only but those levels were significantly higher than
those obtained in mice immunized with protein only. The
establishment of a mouse model that gives similar results with
the macaque model enhances our ability to test many variations
and optimize the vaccine. Importantly, in macaques this
strategy elicited higher binding and neutralizing Ab responses
than DNA only and the neutralizing Abs showed broad activity.
The presence of the EM005 adjuvant further enhanced the
Ab responses. These responses were correlated with the upregulated
activation of dendritic cells by EM005. The longevity
of the Ab response was superior.
Conclusion: The strategy of DNA and protein co-immunization
has potential for development as a prophylactic HIV-1
vaccine. Our challenge studies show that DNA and protein
co-immunized animals developing long-lasting Ab titers were
protected from infection.
266
AIDS Vaccine 2012
P12.52
Viral Vector Delivery of Env Trimer Immunogens
C.L. Parks 1 , S. Rabinovich 1 , P.J. Tiberio 1 , K.J. Wright 1 , M. Yuan 1 ,
M.G. Delboy 1 , M. Kemelman 1 , A.J. Wilson 1 , R.L. Powell 1 ,
S. Hoffenberg 1 , M.J. Chiuchiolo 1 , C. Boggiano 1 , G. Morrow 1 ,
I.C. Lorenz 1 , C.K. Jurgens 1 , X. Zhang 1 , R.W. Lindsay 1 , W.C. Koff 1 ,
C.R. King 1 , M.J. Caulfield 1
1 International AIDS Vaccine Initiative, Brooklyn, NY, USA
Background: Our objective is to develop viral vaccine vectors
that will elicit neutralizing antibodies that are specific for the
functional attachment protein on the HIV particle. To achieve
this goal, we are developing vectors that express membraneanchored
Env trimers that closely mimic authentic functional
glycoprotein spikes.
Methods: We are using vesicular stomatitis virus (VSV)
as a vector platform for delivery of Env immunogens as
transmembrane glycoproteins. We have investigated a variety of
vector designs and Env modifications to identify combinations
that balance the practical requirement for vector genetic
stability with factors influencing antibody responses including
immunogen abundance, efficient post-translational processing,
and presentation of antigenic determinants representative of a
functional trimeric spike.
Results: Substituting domains in Env with analogous regions
from VSV G, we have developed a number of immunogens that
are efficiently expressed and incorporated in the infected cell
plasma membrane, and in most cases, progeny virus particles.
Antigenicity was evaluated using a panel of monoclonal
antibodies specific for various Env epitopes.
Conclusion: We identified modified Env immunogens that contain
determinants for most classes of known broadly neutralizing
monoclonal antibodies including those with specificity for the
CD4 binding site (b12, PGV04), V3 and carbohydrate (PGT126),
the MPER (2F5 and 4E10), the glycan shield (2G12), and structures
formed by V1/V2 and carbohydrate (PG9, PG16, PGT145). Results
from ongoing immunogenicity studies with vectors encoding SIV
or HIV Env immunogens (subtypes A, B, or C) indicate that the
modified trimers elicit antibody responses in small animals and
nonhuman primates, and that some live vectors induce mucosal
antibodies. Study sera are being analyzed for virus neutralization
activity and fine specificity.