Development of a glycoconjugate vaccine to prevent invasive Salmonella Typhimurium infections in sub-Saharan Africa

Invasive infections associated with non-typhoidal Salmonella (NTS) serovars Enteritidis (SE), Typhimurium (STm) and monophasic variant 1,4,[5],12:i:- are a major health problem in infants and young children in sub-Saharan Africa, and currently, there are no approved human NTS vaccines. NTS O-polysaccharides and flagellin proteins are protective antigens in animal models of invasive NTS infection. Conjugates of SE core and O-polysaccharide (COPS) chemically linked to SE flagellin have enhanced the anti-COPS immune response and protected mice against fatal challenge with a Malian SE blood isolate. We report herein the development of a STm glycoconjugate vaccine comprised of STm COPS conjugated to the homologous serovar phase 1 flagellin protein (FliC) with assessment of the role of COPS O-acetyls for functional immunity. Sun-type COPS conjugates linked through the polysaccharide reducing end to FliC were more immunogenic and protective in mice challenged with a Malian STm blood isolate than multipoint lattice conjugates (>95% vaccine efficacy [VE] versus 30-43% VE). Immunization with de-O-acetylated STm-COPS conjugated to CRM197 provided significant but reduced protection against STm challenge compared to mice immunized with native STm-COPS:CRM197 (63-74% VE versus 100% VE). Although OPS O-acetyls were highly immunogenic, post-vaccination sera that contained various O-acetyl epitope-specific antibody profiles displayed similar in vitro bactericidal activity when equivalent titers of anti-COPS IgG were assayed. In-silico molecular modeling further indicated that STm OPS forms a single dominant conformation, irrespective of O-acetylation, in which O-acetyls extend outward and are highly solvent exposed. These preclinical results establish important quality attributes for an STm vaccine that could be co-formulated with an SE-COPS:FliC glycoconjugate as a bivalent NTS vaccine for use in sub-Saharan Africa

CSR committees on boards: the impact of the external country level factors

This article explores the spread of corporate social responsibility (CSR) committees in the European countries, examining whether and what country level external conditions can have a positive impact for their presence on boards. CSR committees are becoming increasingly important as tools of corporate governance to fight corruption, protect stakeholders, create shared value in the long run and, in general, reduce company’s exposure to responsibility failures in a context where the management of CSR is even more complicated. Taking into consideration more than 22,000 boards of European companies from 2000 to 2016, we first developed a descriptive analysis on the level of spread of CSR committees, and then quantitatively prove that the non-financial disclosure mandatory requirements have a positive impact on the presence of CSR committees on boards. This study contributes to the prior studies about the extent to which CSR committees have been adopted by companies and to the existing literature about corporate governance and CSR, supports legislators and regulators by information about the more effective actions to encourage companies in CSR committees’ establishment, and suggests companies a special corporate governance structure to better manage their global responsibility towards stakeholders. Finally, this research can be the starting point for future studies about what industry level factors are potential driver for CSR committees on boards