IAS 2007 - Immune-based Therapies: Pre-clinical Models

Immune-based Therapies: Pre-clinical Models

WEAA2

Type:

Oral abstract session

Back

Venue:

Bayside Auditorium A

Time:

14:30 - 16:00, Wednesday, 25.07.2007

Code:

WEAA2

Co-Chairs:

Anthony Jaworowski, Australia
H. Clifford Lane, United States

Presentations in this session:
14:30
WEAA201
Abstract
Powerpoint (756 KB) Enhanced anti-HIV-1 T cell responses stimulated by dendritic cells loaded with consensus subtype B, wild-type or autologous gag mRNA
Presented by Ellen Van Gulck, Belgium
Van Gulck E.¹, Heyndrickx L.¹, Coppens S.¹, Van Tendeloo V.², Berneman Z.², Vanham G.¹
¹Institute of Tropical Medicine, Microbiology, Antwerp, Belgium, ²Antwerp University Hospital, Medicine, Antwerp, Belgium

14:45
WEAA202
Abstract Improved efficiency and delivery of IL-15 DNA in combination with IL-15 receptor alpha DNA in mice and macaques as vaccine adjuvants and for immunotherapy deliver a potent growth signal for NK and T cells
Presented by George Pavlakis, United States
Bergamaschi C.¹, Jalah R.¹, Rosati M.¹, Valentin A.¹, Kulkarni V.¹, Alicea C.¹, Patel V.¹, Zhang G.-M.¹, Felber B.¹, Pavlakis G.¹
¹National Cancer Institute at Frederick, Center for Cancer Research, Frederick, United States

15:00
WEAA203
Abstract DNA vaccination in the presence of cytokine adjuvants down-regulates PD-1 expression on memory subsets in SIV infected rehsus macaques
Presented by Rabih Halwani, Canada
Halwani R.¹, Boyer J.², Weiner D.², Sekaly R.-P.¹
¹CHUM Reserach Center, Microbiology and Immunology, Montreal, Canada, ²The Penn Center of AIDS Research, Pennsylvania, United States

15:15
WEAA204
Abstract
Powerpoint (1.09 MB) Reduced viremia and delayed disease progression following immunotherapy of SIV with peptide pulsed blood
Presented by Robert De Rose, Australia
De Rose R.¹, Fernandez C.¹, Smith M.¹, Peut V.¹, Batten C.J.¹, Rollman E.¹, Loh L.¹, Alcantara S.¹, Mason R.¹, Law M.², Handley A.³, Kent S.¹
¹University of Melbourne, Microbiology & Immunology, Parkville, Australia, ²University of New South Wales, National Centre in HIV Epidemiology and Clinical Research, Sydney, Australia, ³OPAL Therapeutics, Melbourne, Australia

15:30
WEAA205
Abstract
Powerpoint (1.12 MB) Reduced IL-7Rα expression in CD8 T cells from HIV+ patients is associated with the transcriptional repressor Gfi-1 and impaired STAT activation in response to IL-7 but not IL-2, IL-15, IL-4, and IL-10
Presented by Marko Kryworuchko, Canada
Benoit A.¹, Abdkader K.¹, Sirskyj D.¹, Alhetheel A.¹, Sant N.¹, Angel J.², Kumar A.¹, Diaz-Mitoma F.¹, Kryworuchko M.¹
¹Children's Hospital of Eastern Ontario (CHEO), Infectious Disease and Vaccine Research Centre, CHEO-Research Institute, Division of Virology, CHEO; Depts. Pathology & Laboratory Medicine, and Biochemistry, Microbiology & Immunology, University of Ottawa, Ottawa, ON, Canada, ²Ottawa Hospital - General Campus, Division of Infectious Diseases, Ottawa, ON, Canada

15:45
WEAA2LB
Abstract
Powerpoint (744 KB) Adoptive-transfer studies with semi-inbred cats demonstrate lentivirus-specific CD4+perforin+ CTL and CD8+granzyme-B+/interferon-gamma+ CTL important for a broadly-effective AIDS vaccine
Presented by Janet Yamamoto
Yamamoto J.¹, Pu R.¹, Coleman J.K.¹, Sato E.¹
¹University of Florida, Gainesville FL, United States

Audio files:

audio file - high quality (mp3 format, 45.8 MB)
audio file - low quality (mp3 format, 22.9 MB)

Rapporteur report

Track A: HIV Basic Science report by Gilda Tachedjian
This session covered basic data on signal transduction defects in HIV patients which may impair immune responses in the context of immunotherapy to several preclinical models for immune based therapies.

Van Gulck examined the potential of dendritic cells cultured from monocytes of patients on HAART and electroporated with gag mRNA, to induce autologous T cell responses. Using either autologous gag mRNA or consensus HxB2 gag, both CD4 and CD8 responses were seen. CD4 cells were shown by ELISPOT to produce robust IFNg, IL2 and perforin production while CD8 cells produced both IFNg and perforin but not IL2. These data show the potential of DC-based therapy in the setting of therapy discontinuation.

Using a different approach, termed OPAL, DeRose presented data using a pigtail macaque model in which PBMC were sampled from SIV infected macaques on therapy and controlled viremia, pulsed with a pool of overlapping 15mer peptides covering either SIV Gag or all 9 SIV proteins then reinfused. Therapy was withdrawn and the effect of the peptide-pulsed autologous leukocytes on CD4 and CD8 responses was measured. OPAL “Gag” induced strong Gag-specific responses in both CD4 and CD8 cells whereas OPAL “all” induced a broader response but lower Gag-specific responses presumably due to competition for antigen presentation. Animals receiving OPAL also experienced 0.5-0.7 log reductions in viral load on rebound.

Interleukin 7 and 15 are two cytokines, which increase homeostatic proliferation of T cells as well as positively regulate T cell function. They have been proposed as potential adjuvants in HIV vaccine therapy. In a paper presented by George Pavlakis, IL15 was shown to be more stable and expressed at higher levels if co-expressed with its receptor subunit IL15Ra. Administration of vectors coexpressing both proteins into mice resulted in 3 log increases in IL15 and increased bioactivity as shown by increased NK cell frequency in various tissues. These data support the use of IL15/IL15Ra co-expressing plasmids as a vaccine adjuvant in infectious disease and cancer applications.

In an SIV-infected macaque model, Rabih Halwani showed that an IL12-expressing adjuvant plasmid followed by boosting with an IL15-expressing plasmid increased TEM IFNg and TNFa responses and T cell proliferation when compared to immunising with SIV-expressing plasmids alone. Furthermore, the adjuvant regimen reduced PD1 expression (a marker of “exhausted” CD8+ and CD4+ T cells) thus supporting the incorporation of these cytokine expressing plasmids as vaccine adjuvants.

Kryworuchko presented data showing that IL7 receptor activation of STAT5, which mediates many of the biological activities of this and related cytokines, is defective in PBMC isolated from HIV patients. Defective JAK/STAT signalling in the context of HIV infection has been described for several cytokines and growth factors, but the mechanism(s) is unclear. In the case of IL7, defective signalling was due to specific down regulation of the IL7 receptor which was associated with induction of the transcriptional repressor Gfi-1.Within patient cells, both responsive and non-responsive cells were identified and there was a strong correlation between expression of IL7R and signalling on a per cell basis, but the underlying difference between these populations remains to be identified. What the implication of defective T cell signalling is for vaccine adjuvants is at present unclear.

In a late breaker, Yamamoto presented data on adoptive transfer studies using semi inbred cats to examine the correlates of cellular immunity to FIV induced by a commercial dual subtype FIV vaccine. Purified cell populations from vaccinated cats were transfused into recipients prior to challenge with homologous or heterologous FIV. In both challenge models, protection appeared to be MHC 1 and 2 restricted. Protection was conferred by CD4+ perforin+ and CD8+ granzyme B and IFNg dual positive CTLs.

Add this session to your itinerary and back

Back to the Programme-at-a-Glance

The organizers reserve the right to amend the programme.