Prior infection with unrelated neurotropic virus exacerbates influenza disease and impairs lung T cell responses.

Immunity to infectious diseases is predominantly studied by measuring immune responses towards a single pathogen, although co-infections are common. In-depth mechanisms on how co-infections impact anti-viral immunity are lacking, but are highly relevant to treatment and prevention. We established a mouse model of co-infection with unrelated viruses, influenza A (IAV) and Semliki Forest virus (SFV), causing disease in different organ systems. SFV infection eight days before IAV infection results in prolonged IAV replication, elevated cytokine/chemokine levels and exacerbated lung pathology. This is associated with impaired lung IAV-specific CD8+ T cell responses, stemming from suboptimal CD8+ T cell activation and proliferation in draining lymph nodes, and dendritic cell paralysis. Prior SFV infection leads to increased blood brain barrier permeability and presence of IAV RNA in brain, associated with increased trafficking of IAV-specific CD8+ T cells and establishment of long-term tissue-resident memory. Relative to lung IAV-specific CD8+ T cells, brain memory IAV-specific CD8+ T cells have increased TCR repertoire diversity within immunodominant DbNP366+CD8+ and DbPA224+CD8+ responses, featuring suboptimal TCR clonotypes. Overall, our study demonstrates that infection with an unrelated neurotropic virus perturbs IAV-specific immune responses and exacerbates IAV disease. Our work provides key insights into therapy and vaccine regimens directed against unrelated pathogens.

Development of virus-like particles with inbuilt immunostimulatory properties as vaccine candidates.

The development of virus-like particle (VLP) based vaccines for human papillomavirus, hepatitis B and hepatitis E viruses represented a breakthrough in vaccine development. However, for dengue and COVID-19, technical complications, such as an incomplete understanding of the requirements for protective immunity, but also limitations in processes to manufacture VLP vaccines for enveloped viruses to large scale, have hampered VLP vaccine development. Selecting the right adjuvant is also an important consideration to ensure that a VLP vaccine induces protective antibody and T cell responses. For diseases like COVID-19 and dengue fever caused by RNA viruses that exist as families of viral variants with the potential to escape vaccine-induced immunity, the development of more efficacious vaccines is also necessary. Here, we describe the development and characterisation of novel VLP vaccine candidates using SARS-CoV-2 and dengue virus (DENV), containing the major viral structural proteins, as protypes for a novel approach to produce VLP vaccines. The VLPs were characterised by Western immunoblot, enzyme immunoassay, electron and atomic force microscopy, and in vitro and in vivo immunogenicity studies. Microscopy techniques showed proteins self-assemble to form VLPs authentic to native viruses. The inclusion of the glycolipid adjuvant, α-galactosylceramide (α-GalCer) in the vaccine formulation led to high levels of natural killer T (NKT) cell stimulation in vitro, and strong antibody and memory CD8+ T cell responses in vivo, demonstrated with SARS-CoV-2, hepatitis C virus (HCV) and DEN VLPs. This study shows our unique vaccine formulation presents a promising, and much needed, new vaccine platform in the fight against infections caused by enveloped RNA viruses.

Scaffolding dermatological learning with near-peer teaching for preclinical-year medical students.

BACKGROUND: To date, to our knowledge, there has not been a study on dermatological teaching in the preclinical years (usually the first 2 years of medical school), where the majority of learning takes place in the form of lectures and seminars. Near-peer teaching (NPT) involves students who are at least one academic year more senior imparting knowledge to junior students. The principles behind scaffolding are having a more experienced teacher to guide learning, breaking down learning into smaller tasks and helping to build interest in learning. OBJECTIVES: To investigate the feasibility and effectiveness of NPT in scaffolding dermatological learning among preclinical-year medical students. METHODS: Near-peer teachers who are content experts in dermatology taught alongside conventional teaching with lecturers. We employed five quiz questions before and after the case launch lecture, where students were first exposed to dermatology. We also invited students to provide feedback using a questionnaire on NPT in dermatology at the end of the case 8 teaching week. RESULTS: In total, 74 students participated in the pre- and post-lecture quiz questions, and 47 completed feedback. There was overwhelmingly positive feedback towards NPT, and various learning theories can help explain the success of this project. CONCLUSIONS: Preclinical students enjoy dermatological teaching with the involvement of suitable near-peers. With the professional barrier removed, students can better relate to near-peers (and vice versa). Helping students understand the relevance of dermatology in the clinical setting at an early stage and adopting learning tools such as mnemonics, summary tables, comparison tables and mapping teaching with the learning curriculum clearly helped students learn about dermatology.