Antibody responses to α-Gal in African children vary with age and site and are associated with malaria protection.

Naturally-acquired antibody responses to malaria parasites are not only directed to protein antigens but also to carbohydrates on the surface of Plasmodium protozoa. Immunoglobulin M responses to α-galactose (α-Gal) (Galα1-3Galβ1-4GlcNAc-R)-containing glycoconjugates have been associated with protection from P. falciparum infection and, as a result, these molecules are under consideration as vaccine targets; however there are limited field studies in endemic populations. We assessed a wide breadth of isotype and subclass antibody response to α-Gal in children from Mozambique (South East Africa) and Ghana (West Africa) by quantitative suspension array technology. We showed that anti-α-Gal IgM, IgG and IgG1-4 levels vary mainly depending on the age of the child, and also differ in magnitude in the two sites. At an individual level, the intensity of malaria exposure to P. falciparum and maternally-transferred antibodies affected the magnitude of α-Gal responses. There was evidence for a possible protective role of anti-α-Gal IgG3 and IgG4 antibodies. However, the most consistent findings were that the magnitude of IgM responses to α-Gal was associated with protection against clinical malaria over a one-year follow up period, especially in the first months of life, while IgG levels correlated with malaria risk

Digital information made to measure : an exploration of possibilities and user-demands

A representation is given of an analysis of developments in the access to scientific literature, an overview of the possibilities of co-operation with other libraries and the result of an assessment of the informational needs of its RIVM-users. The Working Group gives recommendations concerning present and future tasks, costs and budgeting and the place of the library in the organisational structure of the RIVM. The most important recommendations are: continuation and acceleration of the policy of digital availability of information, reduction of the in-print collection, broadening the supply of information (other than official scientific literature), setting up an e-archive for RIVM-reports (in co-operation with external partners), institutional co-ordination of the RIVM-Internet and Intranet activities (together with the IT-department), support and facilitating of knowledge management within the institute and cost charging for a part of the library services.Naast een analyse van de ontwikkelingen in de toegang tot de wetenschappelijke literatuur en een inventarisatie van de samenwerkingsmogelijkheden met andere bibliotheken wordt het resultaat van een uitgebreide behoeftepeiling binnen het RIVM gepresenteerd. Aan de hand hiervan komt de Werkgroep bibliotheekfunctie met aanbevelingen t.a.v. huidige en nieuwe taken, kosten en budgettering en de plaats van de bibliotheek in de RIVM-organisatie. De voornaamste aanbevelingen zijn: voorzetting en versnelling van het beleid om informatie digitaal beschikbaar te stellen, de papieren collectie gefaseerd af te bouwen, verbreding van het informatieaanbod (naast de officiele wetenschappelijke literatuur), het (samen met externe partners) opzetten van een e-archive voor RIVM-rapporten, instituutsbrede coordinatie (samen met de IT-afdeling) van de RIVM-Internet- en Intranetactiviteiten, ondersteuning en facilitering van kennismanagement binnen het RIVM en het doorbelasten van een deel van de dienstverlening

Contribution of murine IgG Fc regions to antibody binding to the capsule of Burkholderia pseudomallei

Immunoglobulin G3 (IgG3) is the predominant IgG subclass elicited in response to polysaccharide antigens in mice. This specific subclass has been shown to crosslink its fragment crystallizable (Fc) regions following binding to multivalent polysaccharides. Crosslinking leads to increased affinity through avidity, which theoretically should lead to more effective protection against bacteria and yeast displaying capsular polysaccharides on their surface. To investigate this further we have analyzed the binding characteristics of 2 IgG monoclonal antibody (mAb) subclass families that bind to the capsular polysaccharide (CPS) of Burkholderia pseudomallei. The first subclass family originated from an IgG3 hybridoma cell line (3C5); the second family was generated from an IgG1 cell line (2A5). When the Fc region of the 3C5 IgG3 is removed by proteolytic cleavage, the resulting F(ab')(2) fragments exhibit decreased affinity compared to the full-length mAb. Similarly, when the parent IgG3 mAb is subclass-switched to IgG1, IgG2b, and IgG2a, all of these subclasses exhibit decreased affinity. This decrease in affinity is not seen when the 2A5 IgG1 mAb is switched to an IgG2b or IgG2a, strongly suggesting the drop in affinity is related to the IgG3 Fc region