SummaryOur study investigated the immunomodulatory activities of human plasmaderived serum immunoglobulin (Ig)A. Previous findings seem contradictory indicating either pro-or anti-inflammatory activities. We used serum IgA purified from large plasma pools and studied the modulation of the release of cytokines and chemokines from resting and lipopolysaccharide ( We conclude that human serum IgA has both an anti-inflammatory and a pro-inflammatory capacity and this dual capacity might contribute to the feedback mechanisms maintaining a balance between pro-inflammatory and anti-inflammatory activities.

The new manufacturing process enables the production of a highly purified IgG preparation for intravenous administration. The product has an IgG subclass distribution similar to plasma and contains a broad spectrum of functionally intact antibodies. Preclinical studies demonstrate that the liquid IGIV 10% combines excellent qualities of efficacy, safety and tolerability.

Extensive preclinical safety and pharmacokinetic testing confirmed that this hBChE preparation can be used for further efficacy testing as a bioscavenger for toxic organophosphate compounds in appropriate animal models and ultimately in humans.

West Nile virus (WNV)-neutralizing intravenous immune globulins (IVIG)were fractionated into IgG subclasses, and the contribution of each subclass to in vitro neutralization of and in vivo protection against WNV was evaluated. The results indicate that IgG1 (i) is the main subclass induced following WNV infection of humans, (ii) contained nearly all the in vitro WNV neutralization capacity, and (iii) mediates effector functions in vivo that render it superior to other subclasses in protection against WNV. The importance of human IgG1 indicates that a candidate WNV vaccine should induce an immune response that includes WNV-specific IgG1.West Nile virus (WNV), a flavivirus which has become endemic in North America (1) and has now also been recognized as a major public health concern in Europe (6), causes mostly asymptomatic infections (in ϳ80% of cases), and less than 1% of WNV-infected persons develop neuroinvasive disease (7). There are currently no WNV-specific antiviral drugs available, and treatment of patients is limited to supportive care. To optimize efficacy of a potential vaccine, an understanding of the factors involved in successful WNV clearance after infection of humans is important. Some aspects of the immune response to WNV infection have been studied in detail, especially the affinities and specificities of WNV-neutralizing antibodies (Abs), properties which are crucial for effective virus neutralization (5,8,16,26). During these investigations, it became evident that the murine immune response to WNV differs to some degree from that of humans; e.g., the strongly neutralizing Abs that recognize an epitope on the lateral ridge of domain III of the WNV envelope protein in mice are generated far less frequently in the human immune response (16,27). Reports of protective immune responses following the induction of WNV-specific Abs without virus-neutralizing properties highlighted the involvement of Ab-mediated effector responses such as Ab-dependent cellular cytotoxicity, complement activation, and Ab interaction with Fc-␥ receptors (Fc␥Rs) in protection and immunity (3,14,15). The apparent importance of effector functions beyond virus neutralization in host defense renders an understanding of the profile of human IgG subclasses induced following WNV infection and the respective contributions of the subclasses to in vivo protection particularly interesting. The four human IgG subclasses, IgG1 to IgG4, differ in their affinities for Fc␥Rs and therefore in their abilities to induce effector responses (2). In addition, IgG subclass-dependent effects on in vitro virus neutralization were shown recently for another flavivirus, dengue virus (20). Although accumulating evidence highlights the differential involvement of IgG subclasses in the humoral response against flavivirus infection, no information on the contributions of the different human IgG subclasses to WNV neutralization in vitro and, more importantly, their contributions to in vivo protection is currently available.In this work, we used intraveno...

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