Restriction of HIV-1 Escape by a Highly Broad and Potent Neutralizing Antibody

Broadly neutralizing antibodies (bNAbs) represent a promising approach to prevent and treat HIV-1 infection. However, viral escape through mutation of the HIV-1 envelope glycoprotein (Env) limits clinical applications. Here we describe 1-18, a new V_H1-46-encoded CD4 binding site (CD4bs) bNAb with outstanding breadth (97%) and potency (GeoMean IC₅₀ = 0.048 μg/mL). Notably, 1-18 is not susceptible to typical CD4bs escape mutations and effectively overcomes HIV-1 resistance to other CD4bs bNAbs. Moreover, mutational antigenic profiling uncovered restricted pathways of HIV-1 escape. Of most promise for therapeutic use, even 1-18 alone fully suppressed viremia in HIV-1-infected humanized mice without selecting for resistant viral variants. A 2.5-Å cryo-EM structure of a 1-18-BG505_(SOSIP.664) Env complex revealed that these characteristics are likely facilitated by a heavy-chain insertion and increased inter-protomer contacts. The ability of 1-18 to effectively restrict HIV-1 escape pathways provides a new option to successfully prevent and treat HIV-1 infection

Family Exit in Family Firms: How Network Ties Affect the Owner’s Intention to Follow the Private Equity Succession Route

Kreer F, Mauer R, Limbach P, Brettel M. Family Exit in Family Firms: How Network Ties Affect the Owner’s Intention to Follow the Private Equity Succession Route. Schmalenbach Business Review. 2015;67(4):454-488.We study private equity as a succession route in family firms. Using survey data from Germany, we empirically examine the role owner-managers and their network ties play in the early process of firm succession. Our evidence suggests that network ties, strong ties in particular, matter to owner-managers when they consider a sale to private equity. Applying the Theory of Planned Behavior, we find that subjective norms and attitude explain the intention to sell to private equity investors, while entrepreneurial network ties explain the subjective norm component. We further show that subjective norm mediates the relationship of network ties on intention