Biochemical Characterization and Evaluation of a Brugia malayi Small Heat Shock Protein as a Vaccine against Lymphatic Filariasis

Filarial nematodes enjoy one of the longest life spans of any human pathogen due to effective immune evasion strategies developed by the parasite. Among the various immune evasion strategies exhibited by the parasite, Interleukin 10 (IL-10) productions and IL-10 mediated immune suppression has significant negative impact on the host immune system. Recently, we identified a small heat shock protein expressed by Brugia malayi (BmHsp12.6) that can bind to soluble human IL-10 receptor alpha (IL-10R) and activate IL-10 mediated effects in cell lines. In this study we show that the IL-10R binding region of BmHsp12.6 is localized to its N-terminal region. This region has significant sequence similarity to the receptor binding region of human IL-10. In vitro studies confirm that the N-terminal region of BmHsp12.6 (N-BmHsp12.6) has IL-10 like activity and the region containing the alpha crystalline domain and C-terminus of BmHsp12.6 (BmHsp12.6αc) has no IL-10 like activity. However, BmHsp12.6αc contains B cell, T cell and CTL epitopes. Members of the sHSP families are excellent vaccine candidates. Evaluation of sera samples from putatively immune endemic normal (EN) subjects showed IgG1 and IgG3 antibodies against BmHsp12.6αc and these antibodies were involved in the ADCC mediated protection. Subsequent vaccination trials with BmHsp12.6αc in a mouse model using a heterologous prime boost approach showed that 83% protection can be achieved against B. malayi L3 challenge. Results presented in this study thus show that the N-BmHsp12.6 subunit of BmHsp12.6 has immunoregulatory function, whereas, the BmHsp12.6αc subunit of BmHsp12.6 has significant vaccine potential

Efficient computation of the shapley value for centrality in networks

The Shapley Value is arguably the most important normative solution concept in coalitional games. One of its applications is in the domain of networks, where the Shapley Value is used to measure the relative importance of individual nodes. This measure, which is called node centrality, is of paramount significance in many real-world application domains including social and organisational networks, biological networks, communication networks and the internet. Whereas computational aspects of the Shapley Value have been analyzed in the context of conventional coalitional games, this paper presents the first such study of the Shapley Value for network centrality. Our results demonstrate that this particular application of the Shapley Value presents unique opportunities for efficiency gains, which we exploit to develop exact analytical formulas for Shapley Value based centrality computation in both weighted and unweighted networks. These formulas not only yield efficient (polynomial time) and error-free algorithms for computing node centralities, but their surprisingly simple closed form expressions also offer intuition into why certain nodes are relatively more important to a network. © 2010 Springer-Verlag