Margaret Ackerman

Publications (18) View all

• Article: Natural variation in Fc glycosylation of HIV-specific antibodies impacts antiviral activity.

  Margaret E Ackerman, Max Crispin, Xiaojie Yu, Kavitha Baruah, Austin W Boesch, David J Harvey, Anne-Sophie Dugast, Erin L Heizen, Altan Ercan, Ickwon Choi, Hendrik Streeck, Peter A Nigrovic, Chris Bailey-Kellogg, Chris Scanlan, Galit Alter
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  ABSTRACT: While the induction of a neutralizing antibody response against HIV remains a daunting goal, data from both natural infection and vaccine-induced immune responses suggest that it may be possible to induce antibodies with enhanced Fc effector activity and improved antiviral control via vaccination. However, the specific features of naturally induced HIV-specific antibodies that allow for the potent recruitment of antiviral activity and the means by which these functions are regulated are poorly defined. Because antibody effector functions are critically dependent on antibody Fc domain glycosylation, we aimed to define the natural glycoforms associated with robust Fc-mediated antiviral activity. We demonstrate that spontaneous control of HIV and improved antiviral activity are associated with a dramatic shift in the global antibody-glycosylation profile toward agalactosylated glycoforms. HIV-specific antibodies exhibited an even greater frequency of agalactosylated, afucosylated, and asialylated glycans. These glycoforms were associated with enhanced Fc-mediated reduction of viral replication and enhanced Fc receptor binding and were consistent with transcriptional profiling of glycosyltransferases in peripheral B cells. These data suggest that B cell programs tune antibody glycosylation actively in an antigen-specific manner, potentially contributing to antiviral control during HIV infection.
  The Journal of clinical investigation 04/2013; · 15.39 Impact Factor
• Article: Separation of nonfucosylated antibodies with immobilized FcγRIII receptors.

  Glen R Bolton, Margaret E Ackerman, Austin W Boesch
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  ABSTRACT: Post-translational modifications can dramatically impact protein activity, but identifying such structure:function relationships, as well as capitalizing on functionally enhanced variants, is a significant challenge. Here, affinity chromatography resins that contained immobilized FcγRIII receptors were used to enrich nonfucosylated antibodies 6-9 fold, offering what may be a tractable method for both the identification of post-translational modifications that affect function, as well as a means to enrich variants with enhanced activity. © 2013 American Institute of Chemical Engineers Biotechnol. Prog.,, 2013.
  Biotechnology Progress 03/2013; · 2.34 Impact Factor
• Article: Enhanced phagocytic activity of HIV-specific antibodies correlates with natural production of immunoglobulins with skewed affinity for FcγR2a and FcγR2b.

  Margaret E Ackerman, Anne-Sophie Dugast, Elizabeth G McAndrew, Stephen Tsoukas, Anna F Licht, Darrell J Irvine, Galit Alter
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  ABSTRACT: While development of an HIV vaccine that can induce neutralizing antibodies remains a priority, decades of research have proven that this is a daunting task. However, accumulating evidence suggests that antibodies with the capacity to harness innate immunity may provide some protection. While significant research has focused on the cytolytic properties of antibodies in acquisition and control, less is known about the role of additional effector functions. Here we investigate antibody-dependent phagocytosis of HIV immune complexes, and observe significant differences in the ability of antibodies from infected subjects to mediate this critical effector function. We observe quantitative differences in the capacity of antibodies to both drive phagocytosis and qualitative differences in their FcγR usage profile. We demonstrate that antibodies from controllers and untreated progressors exhibit increased phagocytic activity, altered Fc-domain glycosylation, and skewed interactions with FcγR2a and FcγR2b in both bulk plasma and HIV-specific IgG. While increased phagocytic activity may directly influence immune activation via clearance of inflammatory immune complexes, it is also plausible that Fc receptor usage patterns may regulate the immune response by modulating downstream signals following phagocytosis-driving passive degradation of internalized virus, release of immune modulating cytokines and chemokines, or priming of a more effective adaptive immune response.
  Journal of Virology 03/2013; · 5.40 Impact Factor
• Article: Vaccine design: emerging concepts and renewed optimism.

  Sebastian K Grimm, Margaret E Ackerman
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  ABSTRACT: Arguably, vaccination represents the single most effective medical intervention ever developed. Yet, vaccines have failed to provide any or adequate protection against some of the most significant global diseases. The pathogens responsible for these vaccine-recalcitrant diseases have properties that allow them to evade immune surveillance and misdirect or eliminate the immune response. However, genomic and systems biology tools, novel adjuvants and delivery systems, and refined molecular insight into protective immunity have started to redefine the landscape, and results from recent efficacy trials of HIV and malaria vaccines have instilled hope that another golden age of vaccines may be on the horizon.
  Current opinion in biotechnology 03/2013; · 7.82 Impact Factor
• Article: What mAbs Tell Us about Shapes: Multiple Roads Lead to Rome.

  Galit Alter, Margaret E Ackerman
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  ABSTRACT: In this issue of Immunity, Liao et al. (2013) utilize monoclonal antibodies isolated from RV144 vaccinees to gain key insights into the structural vulnerabilities of the V1-V2 loops of HIV gp120 protein and how they might be associated with vaccine efficacy.
  Immunity 01/2013; 38(1):8-9. · 21.64 Impact Factor