Oral Abstract Session 01 - Global HIV Vaccine Enterprise

SYMPOSIA SESSIONS
32
Symposia Sessions
Symposium 02: Lessons from Clinical Trials
S02.01
RV144 Update: Insights From Correlates of Risk,
Breakthrough Infections, and Animal Studies In The
Context of Future Vaccine Development
J. Kim 1
1Walter Reed Army Institute of Research (WRAIR), Rockville,
MD, USA
Of RV144 vaccine-induced immune responses measured at
peak immunogenicity, 2 weeks post final vaccination, two were
correlated with infection risk. IgA to HIV envelope correlated
directly and IgG to gp120 V2 was inversely correlated with
infection. Analysis of breakthrough viruses further identified
two sites within V2 that showed, positions 169 and 181, that
contained distinct genetic signatures comparing vaccine to
placebo. A post-hoc analysis suggested that there might be
an “early effect” – consistent with an inducible but transient
antibody response. Further work defining the correlates of risk
over time is ongoing. It is not known whether anti-V2 responses
will serve as a correlate for other vaccines. A previous low-dose
intrarectal challenge NHP study looking at Ad26 and MVA-based
SIV vaccines highlighted anti-V2 (SIV) responses as a potential
correlate, and preliminary sequencing of breakthrough SIV from
that study demonstrates genetic signatures within the V2 region.
Taken together these data suggest a hypothesis that anti-V2
responses may have a more general role in protection, and this
concept can be addressed in future clinical trials. The impact of
these developments on current and planned studies of ALVAC
and gp120 will be discussed.
AIDS Vaccine 2012
S02.02
Comparative Immunogenicity of HIV Vaccine
Candidates In The HVTN
N. Frahm 1 , G. Tomaras 2 , D. Montefiori 2 , P. Gilbert 1 , L. Corey 3 ,
J.M. McElrath 1
1 Fred Hutchinson Cancer Research Center, Seattle, WA, USA;
2 Duke University Medical Center, Durham, NC, USA; 3 HIV
Vaccine Trials Network, Seattle, USA
The partial success of the ALVAC/AIDSVAX vaccine in reducing
HIV acquisition in RV144 led to an increased focus on pox/
protein vaccine regimens for the prevention of HIV infection, but
few data exist in humans on the immunogenicity of the newer
generation of poxvirus vectors, and no new GMP-grade proteins
have entered the vaccine pipeline for several years. At the same
time, several new vaccine strategies – vectors, combinations,
adjuvants and delivery technologies – are in phase I studies in
the HVTN, some with dramatic effects on immunogenicity. In
the absence of correlates of protection from HIV acquisition,
the HVTN laboratories aim at providing a broad understanding
of vaccine-induced humoral and cellular immune responses, to
allow for rational decisions on future product development in
light of the recently proposed correlates of risk in RV144.