BackgroundRecently, livestock-associated methicillin-resistant Staphylococcus aureus CC398 has been discovered in animals, livestock farmers and retail meat. This cross-sectional study aimed to determine the spread to persons not in direct contact with livestock in areas with a high density of pig farms.Methodology/Principal FindingsWith a random mailing in 3 selected municipalities in the Netherlands, adult persons were asked to fill in a questionnaire and to take a nose swab. In total, complete information was obtained on 583 persons. Of the 534 persons without livestock-contact, one was positive for MRSA (0.2%; 95% confidence interval, <0.01–1.2). Of the 49 persons who did indicate to be working at or living on a livestock farm, 13 were positive for MRSA (26.5%; 95% confidence interval, 16.1–40.4). All spa-types belonged to CC398.Conclusions/SignificanceLivestock-associated MRSA has a high prevalence in people with direct contact with animals. At this moment it has not spread from the farms into the community.

No abstract

The human immunodeficiency virus type 1 envelope glycoprotein (Env) complex is the principal focus of neutralizing antibody-based vaccines. The functional Env complex is a trimer consisting of six individual subunits: three gp120 molecules and three gp41 molecules. The individual subunits have proven unsuccessful as vaccines presumably because they do not resemble the functional Env complex. Variable domains and carbohydrates shield vulnerable neutralization epitopes on the functional Env complex. The deletion of variable loops has been shown to improve gp120's immunogenicity; however, problems have been encountered when introducing such modifications in stabilized Env trimer constructs. To address these issues, we have created a set of V1/V2 and V3 loop deletion variants in the context of complete virus to allow optimization by forced virus evolution. Compensatory second-site substitutions included the addition and/or removal of specific carbohydrates, changes in the disulfide-bonded architecture of the V1/V2 stem, the replacement of hydrophobic residues by hydrophilic and charged residues, and changes in distal parts of gp120 and gp41. These viruses displayed increased sensitivity to neutralizing antibodies, demonstrating the improved exposure of conserved domains. The results show that we can select for functionally improved Env variants with loop deletions through forced virus evolution. Selected evolved Env variants were transferred to stabilized Env trimer constructs and were shown to improve trimer expression and secretion. Based on these findings, we can make recommendations on how to delete the V1/V2 domain from recombinant Env trimers for vaccine and X-ray crystallography studies. In general, virus evolution may provide a powerful tool to optimize Env vaccine antigens.The human immunodeficiency virus type 1 (HIV-1) envelope glycoprotein complex (Env) is the principal target of vaccine research aimed at raising an antiviral humoral immune response. The isolation of a small number of broadly active neutralizing antibodies from HIV-infected individuals serves as a rationale for the search for vaccines that elicit such antibodies. Although many Env-based HIV-1 vaccines have been tested in preclinical and clinical studies, so far none has raised broadly reactive antibodies that could neutralize diverse primary virus isolates. Thus, relatively straightforward vaccine strategies that worked for other pathogens-for example, the use of unmodified surface antigens-have been explored without satisfactory results for HIV-1, emphasizing the necessity for more-sophisticated vaccine design.The functional HIV-1 Env complex, which mediates viral entry into CD4 ϩ host cells, is a trimer consisting of six individual subunits: three gp120 molecules and three gp41 molecules. The attachment of HIV-1 to a target cell is followed by the fusion of the viral and cellular membranes. First, gp120 binds to the CD4 receptor, a process that induces conformational changes to create and expose the coreceptor binding site (71, 76). The...