Cassandra Berry

Vaccine hesitancy is still a significant barrier to achieving widespread immunity in many communities. In this paper, we evaluated a serious game focusing on vaccination against COVID-19. This study investigates the potential of virtual reality (VR) as an innovative educational tool to address this issue. Focusing on the serious game “Spike Force”, which simulates the mechanisms of the mRNA COVID-19 vaccine, this research evaluates the game’s effectiveness in enhancing participants’ understanding, altering attitudes, and influencing behaviours related to vaccination. Participants engaged with “Spike Force,” and their knowledge, attitudes, and behaviours were assessed through pre- and post-gameplay questionnaires. The findings show that immersive VR experiences can significantly improve vaccine literacy, increase confidence in vaccine-related discussions, and promote positive behavioural changes toward vaccination. These results suggest that VR could play an effective advocacy role for public health education, particularly in combating vaccine hesitancy.

Control programs for emerging influenza are in urgent need of novel therapeutic strategies to mitigate potentially devastating threats from pathogenic strains with pandemic potential. Current vaccines and antivirals have inherent limitations in efficacy, especially with rapid evolutionary changes of influenza viruses. Antibody-based antiviral protection harnesses the natural power of the immune system. Antibodies present prophylactic and therapeutic intervention options for prevention and control of influenza, especially for at-risk populations. Specific monoclonal antibodies are well defined in purity and initial efficacy but polyclonal antibodies are easier to scale-up and cost-effective with long-term efficacy, using batches with broadly neutralizing properties against influenza variants. This review presents the pros and cons of monoclonal versus polyclonal antibody therapy for influenza.

Teaching scientific inquiry in large interdisciplinary classes is a challenge. We describe a creative problem-based learning approach, using a motivational island crisis scenario, to inspire research design. Students were empowered to formulate their individual scientific inquiry and then guided to develop a testable hypothesis, aims, and objectives in designing a research proposal. Personalized data sets matched to the research objectives were provided to individual students for analysis and presentation. This technique helps students to gain critical insights into the global value of interdisciplinary collaboration toward solving complex real-world problems. Students learn the front end of research, how to formulate a line of scientific inquiry and design an innovative research project- both important skills for them as tomorrow's leaders and entrepreneurs

We investigate the associations of three established plasma biomarkers in the context of HIV and treatment-related variables including a comprehensive cardiovascular disease risk assessment, within a large ambulatory HIV cohort. Patients were recruited in 2010 to form the Royal Perth Hospital HIV/CVD risk cohort. Plasma sCD14, sCD163 and CXCL10 levels were measured in 475 consecutive patients with documented CVD risk (age, ethnicity, gender, smoking, blood pressure, BMI, fasting metabolic profile) and HIV treatment history including immunological/virological outcomes. The biomarkers assessed showed distinct associations with virological response: CXCL10 strongly correlated with HIV-1 RNA (p<0.001), sCD163 was significantly reduced among ‘aviraemic’ patients only (p = 0.02), while sCD14 was unaffected by virological status under 10,000 copies/mL (p>0.2). Associations between higher sCD163 and protease inhibitor therapy (p = 0.05) and lower sCD14 with integrase inhibitor therapy (p = 0.02) were observed. Levels of sCD163 were also associated with CVD risk factors (age, ethnicity, HDL, BMI), with a favourable influence of Framingham score <10% (p = 0.04). Soluble CD14 levels were higher among smokers (p = 0.002), with no effect of other CVD risk factors, except age (p = 0.045). Our findings confirm CXCL10, sCD163 and sCD14 have distinct associations with different aspects of HIV infection and treatment. Levels of CXCL10 correlated with routinely monitored variables, sCD163 levels reflect a deeper level of virological suppression and influence of CVD risk factors, while sCD14 levels were not associated with routinely monitored variables, with evidence of specific effects of smoking and integrase inhibitor therapy warranting further investigation.

Type I and III interferons (IFNs) of the innate immune system belong to a polygenic family, however the individual subtype mediators of the antiviral response in viral infections have been hindered by a lack of reagents. Evaluation studies using different IFN subtypes have distinguished distinct protein properties with different efficacies towards different viruses, opening promising avenues for immunotherapy. This review largely focuses on the application of IFN-α/β and IFN-λ therapies for viral infections, influenza, herpes, HIV and hepatitis. Such IFN subtype therapies may help to cure patients with virus infections where no vaccine exists. The ability of cell types to secrete a number of IFN subtypes from a multi-gene family may be an intuitive counterattack on viruses that evade IFN subtype responses. Hence, clinical use of virus-targeted IFN subtypes may restore antiviral immunity in viral infections. Accumulating evidence suggests that individual IFN subtypes have differential efficacies in selectively activating immune cell subsets to enhance antiviral immune responses leading to production of sustained B and T cell memory. Cytokine therapy can augment innate immunity leading to clearance of acute virus infections but such treatments may have limited effects on chronic virus infections that establish lifelong latency. Therefore, exploiting individual IFN subtypes to select those with the ability to sculpt protective responses as well as reinstating those targeted by viral evasion mechanisms may inform development of improved antiviral therapy.

The surface haemagglutinin (HA) glycoprotein is the immunogenic target for most of the influenza virus immune responses and consists of a globular head and a stalk domain. Recent advances have been made towards the design of a universal influenza virus vaccine to protect against different virus strains based on conserved domains of the HA molecule eliciting broadly neutralising antibodies (bnAb). Development of a universal vaccine for influenza that induces long-lived cross-protective immunity would displace the need for annual seasonal vaccination; prediction of circulating strains and vaccine reformulation. Intense research efforts have been focused on enhancing the potency and breadth of vaccine-induced bnAbs. However, knowledge of how such bnAbs are generated and their mechanisms of action are scarce. Experimental 2-step vaccination approaches using prime-boost regimes stimulate the production of bnAbs but they are usually limited in potency and breadth. Adjuvant enhanced vaccination strategies to elicit potent bnAb and improved B cell memory responses will have an immense impact in global health care and pre-pandemic preparation.

Immunological homeostasis in the respiratory tract is thought to require balanced interactions between networks of dendritic cell (DC) subsets in lung microenvironments in order to regulate tolerance or immunity to inhaled antigens and pathogens. Influenza A virus (IAV) poses a serious threat of long-term disruption to this balance through its potent pro-inflammatory activities. In this study, we have used a BALB/c mouse model of A/PR8/34 H1N1 Influenza Type A Virus infection to examine the effects of IAV on respiratory tissue DC subsets during the recovery phase following clearance of the virus. In adult mice, we found differences in the kinetics and activation states of DC residing in the airway mucosa (AMDC) compared to those in the parenchymal lung (PLDC) compartments. A significant depletion in the percentage of AMDC was observed at day 4 post-infection that was associated with a change in steady-state CD11b+ and CD11b− AMDC subset frequencies and significantly elevated CD40 and CD80 expression and that returned to baseline by day 14 post-infection. In contrast, percentages and total numbers of PLDC were significantly elevated at day 14 and remained so until day 21 post-infection. Accompanying this was a change in CD11b+and CD11b− PLDC subset frequencies and significant increase in CD40 and CD80 expression at these time points. Furthermore, mice infected with IAV at 4 weeks of age showed a significant increase in total numbers of PLDC, and increased CD40 expression on both AMDC and PLDC, when analysed as adults 35 days later. These data suggest that the rate of recovery of DC populations following IAV infection differs in the mucosal and parenchymal compartments of the lung and that DC populations can remain disrupted and activated for a prolonged period following viral clearance, into adulthood if infection occurred early in life.

In the event of a novel influenza A virus pandemic, prophylaxis mediated by antibodies provides an adjunct control option to vaccines and antivirals. This strategy is particularly pertinent to unvaccinated populations at risk during the lag time to produce and distribute an effective vaccine. Therefore, development of effective prophylactic therapies is of high importance. Although previous approaches have used systemic delivery of monoclonal antibodies or convalescent sera, available supply is a serious limitation. Here, we have investigated intranasal delivery of influenza-specific ovine polyclonal IgG antibodies for their efficacy against homologous influenza virus challenge in a mouse model. Both influenza-specific IgG and F(ab’)2 reduced clinical scores, body weight loss and lung viral loads in mice treated 1 hour before virus exposure. Full protection from disease was also observed when antibody was delivered up to 3 days prior to virus infection. Furthermore, effective prophylaxis was independent of a strong innate immune response. This strategy presents a further option for prophylactic intervention against influenza A virus using ruminants to generate a bulk supply that could potentially be used in a pandemic setting, to slow virus transmission and reduce morbidity associated with a high cytokine phenotype.