NspA is a conserved membrane protein that elicits protective antibody responses in mice against Neisseria meningitidis. A recent crystallographic study showed that NspA adopts an eight-stranded ␤-barrel structure when reconstituted in detergent. In order to define the segments of NspA-containing epitopes recognized by protective murine anti-NspA antibodies, we studied the binding of two bactericidal and protective anti-NspA monoclonal antibodies (MAbs), AL12 and 14C7. Neither MAb binds to overlapping synthetic peptides (10-mers, 12-mers, and cyclic 12-mers) corresponding to the entire mature sequence of NspA, or to denatured recombinant NspA (rNspA), although binding to the protein can be restored by refolding in liposomes. Based on the ability of the two MAbs to bind to Escherichia coli microvesicles prepared from a set of rNspA variants created by site-specific mutagenesis, the most important contacts between the MAbs and NspA appear to be located within the LGG segment of loop 3. The conformation of loop 2 also appears to be an important determinant, as particular combinations of residues in this segment resulted in loss of antibody binding. Thus, the two anti-NspA MAbs recognize discontinuous conformational epitopes that result from the close proximity of loops 2 and 3 in the three-dimensional structure of NspA. The data suggest that optimally immunogenic vaccines using rNspA will require formulations that permit proper folding of the protein.

Global initiatives and recent G8 commitments to health systems strengthening have brought increased attention to factors affecting health system performance. While equity concerns and human rights language appear often in the global health discourse, their inclusion in health systems efforts beyond rhetorical pronouncements is limited. Building on recent work assessing the extent to which features compatible with the right to health are incorporated into national health systems, we examine how health systems frameworks have thus far integrated human rights concepts and human rights-based approaches to health in their conceptualisation. Findings point to the potential value of the inclusion of human rights in these articulations to increase the participation or involvement of clients in health systems, to broaden the concept of equity, to bring attention to laws and policies beyond regulation and to strengthen accountability mechanisms.

As one viewpoint of three in the PLoS Medicine Debate on whether drug companies are living up to their human rights responsibilities, Sofia Gruskin and Zyde Raad argue that companies' actions to promote access to medicines, including their interactions with state and non-state actors, must be better monitored.