Oral Abstract Session 01 - Global HIV Vaccine Enterprise

Oral Abstract Session 09: Clinical Trials
OA09.01
Safety and Immunogenicity of a Randomized
Phase I Prime-Boost Trial with ALVAC-HIV (vCP205)
and gp160 MN/LAI-2 Adjuvanted in Alum or
Polyphosphazene
R.J. O’Connell 1 , V.R. Polonis 1 , S. Ratto-Kim 1 , J. Cox 2 ,
L.L. Jagodzinski 1 , J. Malia 1 , N.L. Michael 1 , J. Excler 1 , M.L. Robb 1 ,
J.H. Kim 1
1 U.S.Military HIV Research Program, Bethesda, MD, USA;
2 International AIDS Vaccine Initiative, New York, NY, USA
Background: ALVAC-HIV prime/HIV-1 Env protein boost regimens
have shown HIV-specific neutralizing antibody (NAb) and cellmediated
immune responses, but the impact of protein subunit
schedule and adjuvant requires further definition.
Methods: A Phase 1 trial was conducted in two parts. In Part
A, (open-label) 19 volunteers received oligomeric gp160 MN/
LAI-2 (ogp160) with a dose escalation (25, 50, 100 μg). In Part
B, 72 volunteers (60 active, 12 placebo) received placebo or
recombinant canarypox expressing HIV-1 antigens, (ALVAC-HIV,
vCP205) prime with different doses and schedules of ogp160MN/
LAI-2 in alum or polyphosphazene (PCPP).
Results: The vaccines were safe and well tolerated with no
vaccine-related serious adverse events. Cumulative chromium
release CTL frequency was 37%, and 54% of volunteers showed
proliferative responses to HIV antigens. Lymphoproliferative
CD4+, HIV-specific responses were seen in 53% of ogp160 only
and 57% of prime-boost recipients, respectively. Induced binding
antibody to ogp160 was dose-dependent. NAb responses to
vaccine homologous Tier 1 HIV-1 MN were seen in 99% of vaccine
recipients. While NAb to the heterologous Tier 2 US-1 (R5, clade
B) pseudovirus was negative in all volunteers tested using TZMbl
cells, in a PBMC-based assay, US-1 primary isolate Nab was
induced in 2/19 (10.5%) recipients of ogp160 protein alone and
in 5/30 (16.7%) prime-boost volunteers who received ogp160
in PCPP. Primary isolate neutralization was observed more
frequently overall in recipients of ogp160 in PCPP, as compared
with alum (p=0.027). Using an intracellular p24 flow-cytometry
assay, sera from an ALVAC-HIV/ogp160 recipient demonstrated
94% neutralization of US-1.
Conclusion: A small percentage of vaccine recipients developed
Nab to heterologous primary isolates, responses that to our
knowledge have not been previously described. These results
constitute proof of concept that Tier 2 NAb can be elicited by
vaccination in humans, and underscore the importance of
further optimization of prime-boost vaccination and adjuvanting
strategies for HIV-1 prevention.
Oral Abstract Sessions
OA09.02
In Vivo Targeting of HIV Gag to Dendritic Cells in
Combination with Poly ICLC Is Safe and Immunogenic
in Healthy Volunteers
M. Caskey 1 , C. Trumpfheller 1 , S. Pollak 1 , L. Sinnenberg 1 , A. Hurley 1 ,
J. Pring 1 , I. Shimeliovich 1 , B. Yipp 1 , N. Anandasabapathy 1 ,
S. Mehandru 1 , P. Sarma 1 , R. Koup 1 , R. Bailer 1 , G. Tomaras 2 ,
A. Sato 3 , T. Keler 4 , R. Steinman 1 , S. Schlesinger 1
1 The Rockefeller University, New York, NY, USA; 2 Duke
University, Durham, NC, USA; 3 Statistical Center for HIV/AIDS
Research & Prevention (SCHARP), Seattle, WA, USA; 4 Celldex
Therapeutics, NJ, USA
Background: In vivo delivery of HIV antigens within α-DEC 205
antibodies to maturing dendritic cells (DCs) in combination
with maturation stimuli is a potential new vaccine platform.
This phase-I study evaluates the safety and immunogenicity of
DEC-targeting of HIV gag p24 in combination with poly ICLC in
healthy volunteers.
Methods: 45 volunteers aged 18-60 were enrolled. 9
volunteers per dosage group (low: 0.3mg; mid: 1.0mg; high:
3.0mg) received α-DEC205-HIVp24 mAb plus a fixed dose
of poly ICLC s.c., 3 volunteers received poly ICLC only, and 3
volunteers received saline, in a randomized double-blinded
dose escalation design. Volunteers were vaccinated at weeks 0,
4, 12 and followed for 12 months.
Results: Study remains blinded. Transient local and systemic
reactogenicity occurred, without vaccine-related serious adverse
events to date. Gag p24-specific IgG was induced in 9/15 (60%,
9 received vaccine plus adjuvant) volunteers in both low dose
and mid dose groups at weeks 4, 8, 12, and 16. IgG titers were
higher in the mid dose group and responses persisted for at least
6 months after last low dose immunization. Gag-specific CD4+ T
cells were also detected following immunizations. IL-2 and TNF-α
were the predominant cytokines. For CD4+ cells producing IL-2
or TNF-α, the response rates ranged from 33 to 46% (5-7/15
volunteers, 9 received vaccine plus adjuvant) and 8 to 40% (1-
6/15 volunteers) post-vaccination in the low and mid dose groups
respectively. Among positive responders, the median magnitude
across visits ranged from 0.09% to 0.23% in the low dose group
and from 0.06% to 0.17% in the mid dose group.
Conclusion: This novel DC-targeted protein HIV vaccine in
combination with poly ICLC is safe and immunogenic in humans.
Cellular and humoral immune responses are induced. Antibody
responses are durable, with antibody titers unchanged at 6
months following last immunization.
AIDS Vaccine 2012
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ORAL ABSTRACT SESSIONS