|Friday, February 24th|
An RNA Vaccine Protects against Crimean-Congo Hemorrhagic Fever Virus Infection in Mice
Shanna S. Leventhal, University of Montana and NIAID
10:00 AM - 10:15 AM
Crimean-Congo Hemorrhagic Fever Virus (CCHFV) is commonly transmitted by ticks and has a wide geographic distribution, being endemic throughout southern and eastern Europe, the Middle East, Asia, and Africa. Due to climate change, this range is even expanding northward. CCHFV causes a hemorrhagic disease characterized by initial non-specific illness (fever, muscle pains, nausea) followed by severe internal and external bleeding with a case fatality rate of 5-60%. As there is no licensed therapeutics or vaccines, there is great need for highly effective countermeasures. Recently, we have developed a self-replicating RNA-based vaccine which expresses two of the viral proteins: the CCHFV nucleoprotein (repNP) and glycoprotein precursor (repGPC) and is highly protective against a lethal viral challenge in mice.
We found that vaccination with this vaccine prevented disease and conferred 100% survival against a lethal CCHFV infection in mice. This vaccine significantly stimulated both antibody-producing B-cells and T-cells which kill infected cells. Our repNP vaccination primarily stimulated B-cells to produce anti-NP antibodies while repGPC primarily stimulated the T-cells. To confirm whether B-cells or T-cells are most responsible for protection, we vaccinated mice lacking B- or T-cells. While mice lacking T-cells survived, B-cell deficient mice only had ~40% survival indicating that the B-cells and antibodies are essential to confer protection. Currently, this vaccine is undergoing further preclinical testing in preparation for human clinical trials while ongoing studies are continuing to investigate how these antibodies protect against CCHFV so that we may improve additional and much needed CCHFV therapeutics.
This research was funded by the Intramural Research Program, NIAID, NIH.
A Disease-Causing Mutation in the Human GABA Transporter SLC6A1
10:20 AM - 10:35 AM
GABA (gamma-aminobutyrate) is the primary inhibitory neurotransmitter in mammalian brain. Mutations in the major GABA transporter gene SLC6A1 are associated with pediatric neurological disorders including autism and epilepsy. Understanding the molecular and electrophysiological changes associated with these mutations is crucial for developing patient therapies. In this study we characterized the effects of a spontaneous mutation (S295L) discovered in a heterozygous child experiencing severe neurological symptoms. Expression of the mutant transporter in Xenopus oocytes indicated a complete loss-of-function mutation. Using CRISPR-transgenic SLC6A1 mice, we characterized GABA homeostasis, seizure activity, and synaptic transmission in wild-type, heterozygous, and homozygous animals by measuring radioactive GABA uptake in brain and by patch-clamping cortical neurons. Neither the amplitude nor frequency of miniature GABA-mediated postsynaptic currents (mIPSCs) were changed in the S295L mutants. However, tonic GABAA and GABAB receptor signaling were modestly increased, reflecting an S295L allele-dependent increase in ambient extracellular GABA. Because SLC6A1 is believed to be the primary GABA transporter in brain, the relatively modest effect of its loss on ambient [GABA] was surprising. The potential compensating effect of SLC6A11, another brain GABA transporter, was examined in the mutant mice. The SLC6A11 blocker SNAP5114 did not affect [3H]GABA uptake in wild-type brain, while a significant SNAP5114-sensitive component of GABA uptake was revealed in brains from mutant mice, suggesting that an increase in SLC6A11 transport partially compensates for the loss of SLC6A1. Surprisingly, a similar effect of SNAP5114 was also revealed in wild-type mouse brain when it was applied in combination with SKF89976, an SLC6A1-selective blocker. Using MATLAB, a model incorporating transporter kinetics and GABA diffusion was constructed that can account for this non-linear interaction. We are currently pursuing pre-clinical studies with the SLC6A1-S295L transgenic mice to test the therapeutic efficacy of increasing GABA transport using novel pharmacological activators or gene replacement with viral vectors.
Professional Dispositions Among Counselor Education Doctoral Students
Sabina R. Sabyrkulova
11:00 AM - 11:15 AM
The instructional standards of Counselor Education and Supervision programs expect doctoral students to display professional behavior as they fulfill their five main roles in the program: counseling, supervision, teaching, research, and advocacy (CACREP, 2016). A professional disposition is important because of the close working relationships that doctoral students engage in with peers, students, and faculty. These relationships directly impact learning experiences and development of professional identities for doctoral candidates. Existing studies explore professional dispositions predominantly among master-level counseling students (Guardia, 2020; Brown, 2013) and counselor educators (Brown-Rice & Furr, 2019), but only one study involves doctoral students (Brown-Rice &Furr, 2019).
This study of doctoral students by Brown-Rice and Furr (2019) quantitatively identifies the causes of unprofessional dispositions, such as inability to regulate emotions, demonstration of inadequate clinical skills, and engagement in unethical behavior. While causes are important to identify, examining the actual experiences and processes involving professional dispositions is essential as it will offer the necessary guidance to faculties and doctoral students in managing unprofessional behaviors.
This proposal involves a qualitative study using a grounded theory that explores the experiences of counselor educators who receive concerns about professional dispositions among doctoral students and the process of attending to these concerns. This study holds significance because doctoral programs must identify whether students present appropriate “fitness” for the profession, including self-awareness and emotional stability. It aims to establish clear regulations in addressing professional dispositions. This study expects to facilitate discussions on ethical considerations, including multiculturalism and social justice. Most importantly, this study will allow doctoral students to engage in self-reflection which will contribute to further growth and development on personal and professional levels. Lastly, the outcomes of this study will offer practical implications on responding to professional dispositions in counseling and related disciplines.
Impact of Eating Disorder Recovery on Communication of Identity Through Food
Rosemary F. Jeter
11:20 AM - 11:35 AM
Despite remaining stigmatized and regarded as taboo, eating disorders (EDs) affect millions of people around the world. They are also one of the deadliest mental health disorders, with over thousands of suicides every year being tied to EDs. Recovery from eating disorders is possible; however, there is an ongoing debate about what successful or complete recovery looks like. Most extant research about eating disorder recovery (EDR) is through clinical and biomedical perspectives. However, our understanding of how EDR impacts an individual’s identity is still lacking.
When an individual experiences an illness or mental health disorder, such as an ED, they will commonly incorporate that experience into their identity via modified beliefs, physical adaptations and emotional realignment—a phenomenon known as adopting an illness identity. A similar phenomenon will likely occur when they experience EDR, in which they adopt a recovery identity. In general, individuals want to have their identity respected and affirmed, which requires an understanding of how they manage and thus communicate their identity. Food is a form of non-verbal communication, often steeped in cultural and personal beliefs and values. Humans also need to communicate about food regularly, particularly when they are in EDR. Thus, food is potentially an important part of an individual in DR’s identity, and an important method in which they communicate their identity. This study seeks to understand how individuals in EDR communicate their identity through food, and how they communicate about food.
This study will utilize semi-structured interviews with adults who have been in EDR for at least one year in order to better understand how EDR impacts the ways in which individuals communicate their identity through food, as well as how it impacts the ways individuals communicate about food.