Biology subjects

Carolin, A.

Publications and source records attributed to Carolin, A..

3 recordsLinked to original sources

bioRxiv2025

Insect-specific Yada Yada virus chimeric vaccines protect against chikungunya and Ross River virus-induced arthritis

Arthritogenic alphaviruses such as chikungunya virus (CHIKV) and Ross River virus (RRV) are mosquito-borne viruses that can cause debilitating polyarthritis/polyarthralgia in humans. Although two CHIKV vaccines have been licensed, there are no licensed vaccines for RRV. Herein we generate a host-restricted, insect-specific alphavirus, Yada Yada virus (YYV), chimeric vaccine for CHIKV (YYV-CHIKVMauritius) and for RRV (YYV-RRVTT). YYV-CHIKVMauritius and YYV-RRVTT was able to replicate in C6/36 mosquito cells to similar titres as wild-type CHIKV and RRV. YYV-CHIKVMauritius was also neutralised by CHIKV monoclonal antibodies to the same titres as wild-type CHIKV, indicating its potential as a diagnostic antigen to detect neutralising CHIKV antibodies in human or animal sera. YYV-CHIKVMauritius further demonstrated protection against CHIKV infection and disease in a wild-type mouse model. Two doses of YYV-CHIKVMauritius showed anti-CHIKV ELISA and neutralising antibody responses, with protection against foot swelling, viraemia and viral feet tissue titres. Protection against CHIKV histopathology including myositis, tendonitis, arthritis, subcutaneous oedema and haemorrhage was also observed. YYV-RRVTT also demonstrated protection against RRV infection and disease in a wild-type mouse model, with two vaccine doses inducing anti-RRV ELISA and neutralising antibody responses. Protection against foot swelling, viraemia and viral feet tissue titres and RRV histopathology including myositis, tendonitis, arthritis and subcutaneous oedema was also observed. Cross-protection was also evaluated between YYV-CHIKVMauritius and RRV. Although cross-reactive total IgG were observed for YYV-CHIKVMauritius vaccinated mice, this offered no cross-neutralising antibodies and no protection against RRV infection and disease. Overall, our findings show that YYV-CHIKVMauritius and YYV-RRVTT are safe and efficacious vaccines against CHIKV and RRV, respectively, but do not offer cross-protection.

microbiology↗

bioRxiv2024

The effects of iron deficient and high iron diets on SARS-CoV-2 lung infection and disease

The severity of Coronavirus disease 2019 (COVID-19) caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is often dictated by a range of comorbidities. A considerable literature suggests iron deficiency and iron overload may contribute to increased infection, inflammation and disease severity, although direct causal relationships have been difficult to establish. Here we generate iron deficient and iron loaded C57BL/6J mice by feeding low and high iron diets, with mice on a normal iron diet representing controls. All mice were infected with a primary omicron XXB SARS-CoV-2 isolate and lung inflammatory responses were analyzed by histology, immunohistochemistry and RNA-Seq. Compared with controls, iron deficient mice showed no significant changes in lung viral loads or histopathology, whereas, iron loaded mice showed slightly, but significantly, reduced lung viral loads and histopathology. Transcriptional changes were modest, but illustrated widespread dysregulation of inflammation signatures for both iron deficient vs. controls, and iron loaded vs. controls. Some of these changes could be associated with detrimental outcomes, whereas others would be viewed as beneficial. Diet-associated iron deficiency or overload thus induced modest modulations of inflammatory signatures, but no significant histopathologically detectable disease exacerbations. Author summaryA diet deficient in iron can lead to anemia, a widespread problem worldwide. A diet with excessive iron is less common, but can be associated with excessive consumption of iron supplements. We investigate herein using a mouse model, whether low or high iron diets predispose to detrimental outcomes in the lungs after infection with SARS-CoV-2. A considerable literature suggests iron dysregulation would promote infection and inflammation. However, we found, although inflammatory responses showed modest modulations, viral loads were unaffected or slightly reduced, and lung histopathology was either unaffected or indicated slightly less severe disease. These findings do not support a view that low or high iron diets represent comorbidities predisposing to overt detrimental outcomes for acute COVID-19 lung disease.

pathology↗

bioRxiv2024

Tracking inflammation resolution signatures in lungs after SARS-CoV-2 omicron BA.1 infection of K18-hACE2 mice

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causes Coronavirus Disease 2019 (COVID-19), which can result in severe disease, often characterised by a cytokine storm and the associated acute respiratory distress syndrome. However, many infections with SARS-CoV-2 are mild or asymptomatic throughout the course of infection. Although blood biomarkers of severe disease are well studied, less well understood are the inflammatory signatures in lung tissues associated with mild disease or silent infections, wherein infection and inflammation are rapidly resolved leading to sequelae-free recovery. Herein we described RNA-Seq and histological analyses of lungs over time in an omicron BA.1/K18-hACE2 mouse infection model, which displays these latter features. Although robust infection was evident at 2 days post infection (dpi), viral RNA was largely cleared by 10 dpi. Acute inflammatory signatures showed a slightly different pattern of cytokine signatures compared with severe infection models, and where much diminished 30 dpi and absent by 66 dpi. Cellular deconvolution identified significantly increased abundance scores for a number of anti-inflammatory pro-resolution cell types at 5/10 dpi. These included type II innate lymphoid cells, T regulatory cells, and interstitial macrophages. Genes whose expression trended downwards over 2 - 66 dpi included biomarkers of severe disease and were associated with cytokine storm pathways. Genes whose expression trended upward during this period were associated with recovery of ciliated cells, AT2 to AT1 transition, reticular fibroblasts and innate lymphoid cells, indicating a return to homeostasis. Very few differentially expressed host genes were identified at 66 dpi, suggesting near complete recovery. The parallels between mild or subclinical infections in humans and those observed in this BA.1/K18-hACE2 mouse model are discussed with reference to the concept of "protective inflammation".

immunology↗