Liposomal vaccines incorporating molecular adjuvants and intrastructural T-cell help promote the immunogenicity of HIV membrane-proximal external region peptides

An HIV vaccine capable of inducing high and durable levels of broadly neutralizing antibodies has thus far proven elusive. A promising antigen is the membrane-proximal external region (MPER) from gp41, a segment of the viral envelope recognized by a number of broadly neutralizing antibodies. Though an attractive vaccine target due to the linear nature of the epitope and its highly conserved sequence, MPER peptides are poorly immunogenic and may require display on membranes to achieve a physiological conformation matching the native virus. Here we systematically explored how the structure and composition of liposomes displaying MPER peptides impacts the strength and durability of humoral responses to this antigen as well as helper T-cell responses in mice. Administration of MPER peptides anchored to the surface of liposomes induced MPER-specific antibodies whereas MPER administered in oil-based emulsion adjuvants or alum did not, even when combined with Toll-like receptor agonists. High-titer IgG responses to liposomal MPER required the inclusion of molecular adjuvants such as monophosphoryl lipid A. Anti-MPER humoral responses were further enhanced by incorporating high-Tm lipids in the vesicle bilayer and optimizing the MPER density to a mean distance of ∼10–15 nm between peptides on the liposomes' surfaces. Encapsulation of helper epitopes within the vesicles allowed efficient “intrastructural” T-cell help, which promoted IgG responses to MPER while minimizing competing B-cell responses against the helper sequence. These results define several key properties of liposome formulations that promote durable, high-titer antibody responses against MPER peptides, which will be a prerequisite for a successful MPER-targeting vaccine.Bill & Melinda Gates FoundationNational Institutes of Health (U.S.) (AI091693

Sodium Lauryl Sulfate Abrogates Human Immunodeficiency Virus Infectivity by Affecting Viral Attachment

The microbicidal activity of sodium lauryl sulfate (SLS) against human immunodeficiency virus type 1 (HIV-1) was studied in cultured cells. Pretreatment of HIV-1(NL4-3) with SLS decreased, in a concentration-dependent manner, its infectivity when using 1G5 as target cells. In the absence of a viral pretreatment period or when 1G5 cells were pretreated with SLS, the surfactant-induced inactivation of viral infectivity was less pronounced, especially at concentrations between 375 and 550 μM. SLS had no effect on HIV-1 when the virus was adsorbed to 1G5 cells by a 2-h incubation period. SLS almost completely inhibited the fusion process by decreasing the attachment of HIV-1 to target cells. SLS also inhibited the infectivity of HIV-1-based luciferase reporter viruses pseudotyped with the amphotropic murine leukemia virus envelope (which enters cells in a CD4-, CCR5-, and CXCR4-independent manner), indicating that SLS may inactivate other envelope viruses. In contrast, no effect was seen with vesicular stomatitis virus envelope glycoprotein G (which enters cells through receptor-mediated endocytosis) pretreated with up to 700 μM SLS. SLS also decreased, in a dose-dependent manner, the HIV-1-dependent syncytium formation between 1G5 and J1.1 cells after a 24-h incubation. The reduction of luciferase activity was more pronounced when J1.1 cells (which express HIV-1 proteins on their surface) were pretreated with SLS rather than 1G5 cells. Taken together, our results suggest that SLS could represent a candidate of choice for use in vaginal microbicides to prevent the sexual transmission of HIV and possibly other pathogens causing sexually transmitted diseases

A comparative content analysis of media reporting of sports betting in Australia: Lessons for public health media advocacy approaches

© 2017 The Author(s). Background: Harmful gambling is a significant public health issue. There has been widespread discussion in the Australian media about the extent and impact of sports betting on the Australian community, particularly relating to young men and children. Given the role th at the media plays in influencing policy change and political agendas, and the acknowledgement that media based advocacy is a fundamental component of successful advocacy campaigns, this research aimed to investigate how different stakeholder groups discuss sports betting within the Australian print media. The study uses this information to provide recommendations to guide public health media advocacy approaches. Methods: A quantitative content analysis of print media articles was conducted during two significant Parliamentary Inquiries about sports betting - (1) The Joint Select Committee Inquiry into the Advertising and Promotion of Gambling Services in Sport (2012/2013), and (2) 'The Review of Illegal Offshore Wagering (2015/2016). A total of 241 articles from 12 daily Australian newspapers were analysed. Statistical analysis was used to compare frequency of, and changes in, themes, voices and perspectives over time. Results: Discussions about the marketing and communication of sports betting was a main theme in media reporting (n = 165, 68.5%), while discussions about gambling reform decreased significantly across the two time periods (p < 0.0001). The presence of sports betting industry (p < 0.0001), sporting code (p < 0.0001) and public health expert (p = 0.001) voices all increased significantly across the two time periods. There were very few (n = 11, 4.6%) voices from those who had experienced gambling harm. Finally, while there were significantly fewer articles taking the perspective that regulation changes were needed to protect vulnerable sub-populations (p < 0.0001), articles that had a neutral perspective about the need for regulation change increased significantly across the two time periods (p < 0.0001). Discussion and conclusions: Mapping the media reporting of sports betting is important in developing effective public health advocacy approaches. This study indicates that discussions about the marketing strategies utilised by the sports betting industry was still a main theme in media articles. However, discussions relating to sports betting reforms, in particular to protect individuals who may be vulnerable to the harm associated with these products and their promotional strategies (for example children and young men) decreased during the time periods. Public health advocates may seek to address the decrease in media reports about reform by developing clear evidence-based messages about why regulatory reform is needed, as well as the potential consequences of not implementing reforms. Working with organisations to build capacity for people who have experienced gambling harm may help ensure that individuals with a lived experience of harm have an increased voice in the media