Ryan Beveridge

Cyclic GMP-AMP (cGAMP) is an immunostimulatory second messenger produced by cGAS that activates STING. Soluble cGAMP acts as an adjuvant when administered with antigens. cGAMP is also incorporated into enveloped virus particles during budding. We hypothesised that inclusion of the adjuvant cGAMP within viral vaccine vectors would promote adaptive immunity against vector antigens. We immunised mice with virus-like particles (VLPs) containing the HIV-1 Gag protein and VSV-G. Inclusion of cGAMP within these VLPs augmented splenic VLP-specific CD4 and CD8 T cell responses. It also increased VLP- and VSV-G-specific serum antibody titres and enhancedin vitrovirus neutralisation. The superior antibody response was accompanied by increased numbers of T follicular helper cells in draining lymph nodes. Vaccination with cGAMP-loaded VLPs containing haemagglutinin induced high titres of influenza A virus neutralising antibodies and conferred protection following subsequent influenza A virus challenge. Together, these results show that incorporating cGAMP into VLPs enhances their immunogenicity, making cGAMP-VLPs an attractive platform for novel vaccination strategies.Short summary: cGAMP is an innate immune signalling molecule that can be transmitted between cells by inclusion in enveloped virions. This study demonstrates enhanced immunogenicity of HIV-derived virus-like particles containing cGAMP. Viral vectors loaded with cGAMP may thus be potent vaccines.

Motion-onset visually evoked potentials (mVEPs) are neural potentials that are time-locked to the onset of motion of evoking stimuli. Due to their visually elegant properties, mVEP stimuli may be suited to video game control given gaming’s inherent demand on the users’ visual attention and the requirement to process rapidly changing visual information. Here, we investigate mVEPs associated with 5 different stimuli to control the position of a car in a visually rich 3D racing game in a group of 15 BCI naïve teenagers and compared to 19 BCI naive adults. Results from an additional 14 BCI experienced adults were compared to BCI naïve adults. Our results demonstrate that game control accuracy is related to the number of trials used to make a decision on the users’ chosen button/stimulus (76%, 62% and 35% for 5, 3 and 1 trials, respectively) and information transfer rate (ITR) (13.4, 13.9 and 6.6 bits per minute (BPM)), although, even though accuracy decreases when using three compared to the commonly used five trial repetitions, ITR is maintained. A Kruskal-Wallis test suggests that BCI naïve adults do not outperform BCI naïve teenagers in the 3D racing game in the first and seconds laps (p>0.05), but do outperform in the third lap (p0.05).

Motion-onset visual evoked potentials (mVEPs) are time- and phase-locked brain responses to motion-related stimuli. An mVEP response provides robust features for brain-computer interface (BCI) applications and has the added benefit of being less visually fatiguing than other visual evoked potentials (VEPs). In this study an mVEP BCI that enables control of a visually rich, three-dimensional (3D) car-racing video game is evaluated. A group of 15 teenage schoolchildren (13–16 years old) participated in a single session while they attended a summer school. Participants were asked to control the direction of a car within a realistic racing circuit, where the position of the car was controlled by focusing on one of five motion-related stimuli. Classification accuracy (%) and information transfer rate (ITR) (bits per minute (bpm)) results were encouraging, with participants achieving an average online accuracy of 72% (12 bpm) in the first lap, 67% (10 bpm) in the second lap and 65% (10 bpm) in the third lap (chance accuracy and ITR is 20% and zero bpm). The study shows for the first time the feasibility of using the mVEP paradigm in a commercial-grade car-racing video game. It is also one of the first reports on the performance of a group of teenagers using a BCI.