IAS 2007 - Everything You Wanted to Know about Adaptive Immunity but Were Afraid to Ask

Everything You Wanted to Know about Adaptive Immunity but Were Afraid to Ask

WEAA1

Type:

Oral abstract session

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Venue:

Bayside Auditorium A

Time:

11:00 - 12:30, Wednesday, 25.07.2007

Code:

WEAA1

Co-Chairs:

Simon Mallal, Australia
John Zaunders, Australia

Presentations in this session:
11:00
WEAA101
Abstract
Powerpoint (1.87 MB) Mapping the specificity of neutralizing HIV immune sera
Presented by James Binley, United States
Binley J.¹, Jiang P.¹, Richman D.², Shrestha D.¹, Moore P.³, Robinson J.⁴, Crooks E.¹
¹TPIMS, San Diego, United States, ²UCSD, San Diego, United States, ³NICD, Johannesburg, South Africa, ⁴Tulane University, New Orleans, United States

11:15
WEAA102
Abstract Difficulties in eliciting broadly neutralizing anti-HIV antibodies are not explained by cardiolipin autoreactivity
Presented by Erin M. Scherer, United Kingdom
Scherer E.M.¹, Zwick M.B.², Teyton L.², Burton D.R.²
¹University of Oxford, The Division of Structural Biology, Oxford, United Kingdom, ²The Scripps Research Institute, Department of Immunology, La Jolla, California, United States

11:30
WEAA103
Abstract
Powerpoint (740 KB) No impact of humoral immune responses on controlling viremia during rhesus macaque infection with SIVsmm
Presented by Thaidra Gaufin, United States
Gaufin T.¹, Gautam R.¹, Kasheta M.², Barnes M.¹, Carter A.C.¹, Pattison M.¹, Marx P.A.¹, Kaur A.², Pandrea I.¹, Apetrei C.¹
¹Tulane National Primate Research Center, Covington, United States, ²New England Primate Research Center, Harvard Medical School, Southborough, United States

11:45
WEAA104
Abstract
Powerpoint (3.71 MB) Efficient CD40 signaling and activation of B lymphocytes by HIV-1 particles bearing CD40L
Presented by Michael Imbeault, Canada
Imbeault M.¹, Bélanger D.¹, Ouellet M.¹, Martin G.¹, Tremblay M.J.¹
¹Centre Hospitalier de l'Université Laval, Centre de recherche en Infectiologie, Quebec, Canada

12:00
WEAA105
Abstract The cytolytic potential of SIV Gag specific CD8+ T cells predicts vaccine efficacy
Presented by Erik Rollman, Australia
Rollman E.¹, Smith M.Z.¹, De Rose R.¹, Zuber B.², Kent S.¹
¹University of Melbourne, Department of Microbiology and Immunology, Melbourne, Australia, ²Mabtech AB, Nacka, Sweden

12:15
WEAA106
Abstract Regulatory T cell abnormalities associated with aberrant CD4+ T cell responses in HIV+ patients with immune reconstitution disease (IRD)
Presented by Nabila Seddiki, Australia
Seddiki N.¹, Sasson S.¹, Munier M.L.¹, van Bockel D.¹, Zaunders J.², Marriot D.², Pett S.¹, Cooper D.¹, Kelleher A.¹
¹National Centre in HIV Epidemiology and Clinical Research, Darlinghurst, Australia, ²St Vincents Hospital, Darlinghurst, Australia

Audio files:

audio file - high quality (mp3 format, 43.4 MB)
audio file - low quality (mp3 format, 21.7 MB)

Rapporteur report

Track A: HIV Basic Science report by John Zaunders
Binley et al studied the activities of neutralizing antibodies, mapping at which stage of the viral fusion and infection process the antibodies block, such as CD4 binding versus co-receptor binding or fusion. Most antibodies with neutralizing activity inhibit CD4 binding, similar to the well-studied activity of monoclonal antibody b12. They also studied which regions in gp120 are important for binding using defined mutants as well as testing binding with gp120 trimers in the native conformation. This revealed subtle differences in specificities of sera with cross-neutralizing activity, including both CD4 binding site and gp41 antibodies.

Scherer et al studied the similarity of neutralizing antibodies to anti-cardiolipin autoantibodies, as recently reported. They found that 2 well-defined neutralizing antibodies to gp41 show little if any reactivity to autoantigenic phospholipids. Instead, they exhibited similar reactivity to bacterial antigens as other antibodies generated during infections. These results suggest that tolerance of autoantigens is unlikely to explain the rarity of these neutralizing antibodies, but it may be due to the necessity to bind both peptide and membrane lipid moieties within the one epitope.

Gaufin et al studied SIV infection in rhesus macaques with a strain of SIV, isolated from sootey mangabeys, that was particularly sensitive to neutralizing antibody. They depleted B cells in the rhesus macaques using the therapeutic human monoclonal antibody Rituxan prior to SIV infection. The depletion of B cells was highly effective but had little effect on the peak of viral load during primary infection, nor any discernible effect on the later viral set point in chronic infection, suggesting that antibody plays a minor role in controlling viral replication in either acute or chronic infection.

Imbeault et al described studies on the effect of HIV virions directly on B cell activation. HIV particles can contain CD40 ligand (CD40L) that may interact with CD40 on the surface of B cells. This functional interaction has been well defined previously with either antibodies to CD40 or recombinant CD40L. They found, by detailed microarray, PCR and western blotting analysis that many of the genes in B cells known to be modulated by CD40L, are similarly affected by HIV particles containing CD40L. These results may explain the chronic activation of B cells observed in HIV infection.

Rollman et al studied the kinetics of degranulation and IFN-gamma production in the first 5 hours of restimulation of tetramer+ SIV-specific CD8+ T cells with cognate peptide in vitro. They found that SIV-specific CD8+ T cells from pigtail macaques immunized with attenuated virus were more likely to be rapidly cytotoxic than corresponding CD8+ T cells from animals immunized with vaccinia/fowlpox constructs. The latter cells showed much more rapid cytotoxicity and granzyme B expression after the immunized animals were challenged with SIV.

Seddiki et al hypothesised that immune reconstitution disease (IRD) resulted from a deficit of Tregs. Using a recently defined phenotype for Tregs, it was surprisingly found that they were dramatically increased in IRD patients. This was particularly associated with a greatly increased ratio of Tregs to their target effector CD4+ T cells. However, function of the Tregs in IRD patients appeared to be decreased in suppression assays, possibly due to elevations of gamma chain cytokines in the plasma of these subjects.

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