A live RSV vaccine with engineered thermostability is immunogenic in cotton rats despite high attenuation

Respiratory syncytial virus (RSV) is a leading cause of infant hospitalization and there remains no pediatric vaccine. RSV live-attenuated vaccines (LAVs) have a history of safe testing in infants; however, achieving an effective balance of attenuation and immunogenicity has proven challenging. Here we seek to engineer an RSV LAV with enhanced immunogenicity. Genetic mapping identifies strain line 19 fusion (F) protein residues that correlate with pre-fusion antigen maintenance by ELISA and thermal stability of infectivity in live RSV. We generate a LAV candidate named OE4 which expresses line 19F and is attenuated by codon-deoptimization of non-structural (NS1 and NS2) genes, deletion of the small hydrophobic (SH) gene, codon-deoptimization of the attachment (G) gene and ablation of the secreted form of G. OE4 (RSV-A2-dNS1-dNS2-ΔSH-dGm-Gsnull-line19F) exhibits elevated pre-fusion antigen levels, thermal stability, immunogenicity, and efficacy despite heavy attenuation in the upper and lower airways of cotton rats

EGFR interacts with the fusion protein of respiratory syncytial virus strain 2-20 and mediates infection and mucin expression.

Respiratory syncytial virus (RSV) is the major cause of viral lower respiratory tract illness in children. In contrast to the RSV prototypic strain A2, clinical isolate RSV 2-20 induces airway mucin expression in mice, a clinically relevant phenotype dependent on the fusion (F) protein of the RSV strain. Epidermal growth factor receptor (EGFR) plays a role in airway mucin expression in other systems; therefore, we hypothesized that the RSV 2-20 F protein stimulates EGFR signaling. Infection of cells with chimeric strains RSV A2-2-20F and A2-2-20GF or over-expression of 2-20 F protein resulted in greater phosphorylation of EGFR than infection with RSV A2 or over-expression of A2 F, respectively. Chemical inhibition of EGFR signaling or knockdown of EGFR resulted in diminished infectivity of RSV A2-2-20F but not RSV A2. Over-expression of EGFR enhanced the fusion activity of 2-20 F protein in trans. EGFR co-immunoprecipitated most efficiently with RSV F proteins derived from "mucogenic" strains. RSV 2-20 F and EGFR co-localized in H292 cells, and A2-2-20GF-induced MUC5AC expression was ablated by EGFR inhibitors in these cells. Treatment of BALB/c mice with the EGFR inhibitor erlotinib significantly reduced the amount of RSV A2-2-20F-induced airway mucin expression. Our results demonstrate that RSV F interacts with EGFR in a strain-specific manner, EGFR is a co-factor for infection, and EGFR plays a role in RSV-induced mucin expression, suggesting EGFR is a potential target for RSV disease

Memories of Terrebonne 159

Recorded interview and table of contents of interview with Adonise D. Hotard, Delia Price, and Julia J. Higgin

Awareness Is Not Enough: Frequent Use of Water Pollution Information and Changes to Risky Behavior

Hazard information plays an important role in how risk perceptions are formed and what actions are taken in response to risk. While past studies have shown that information on water and air pollution is associated with changes to individual behavior, there is a need for examination of water quality information in the context of environmental disturbances. This study fills that gap by examining water pollution in an active industrial region of the United States—the Galveston Bay of Texas. Using original survey data collected in 2019 of 525 adults living in the Galveston Bay region, logistic regression was used to analyze the association of awareness and use of water pollution information on changes to outdoor activities and consumption of drinking water and/or seafood. Controls for chronic and acute exposure to environmental hazards, environmental knowledge and experience, and demographics were included in the model. The findings indicate frequent use of water quality information is significantly associated with action to reduce risk. On average, an individual who checks water pollution monitoring every day is 26% and 33% more likely to change their outdoor activities and consumption behavior, respectively, than someone who is not aware of this information. There is a need for improvement in pollution data collection and the development of a risk communication framework that facilitates the dissemination of this information in relevant, accessible, and credible ways

Learning from null effects: a bottom-up approach

A critical barrier to generating cumulative knowledge in political science and related disciplines is the inability of researchers to observe the results from the full set of research designs that scholars have conceptualized, implemented, and analyzed. For a variety of reasons, studies that produce null findings are especially likely to be unobserved, creating biases in publicly accessible research. While several approaches have been suggested to overcome this problem, none have yet proven adequate. We call for the establishment of a new discipline-wide norm in which scholars post short ``null results reports'' online that summarize their research designs, findings, and interpretations. To address the inevitable incentive problems that earlier proposals for reform were unable to overcome, we argue that decentralized research communities can spur the broader disciplinary norm change that would bring advantage to scientific advance. To facilitate our contribution, we offer a template for these reports that incorporates evaluation of the possible explanations for the null findings, including statistical power, measurement strategy, implementation issues, spillover/contamination, and flaws in theoretical priors. We illustrate the template’s utility with two experimental studies focused on the naturalization of immigrants in the United States and attitudes toward Syrian refugees in Jordan