bioRxiv Science⌕ Search

Biology subjects

Valenti, M. T.

Publications and source records attributed to Valenti, M. T..

2 recordsLinked to original sources

Immunogenicity and pre-clinical efficacy of an OMV-based SARS-CoV-2 vaccine

The vaccination campaign against SARS-CoV-2 relies on the world-wide availability of effective vaccines, with a potential need of 20 billion vaccine doses to fully vaccinate the world population. To reach this goal, the manufacturing and logistic processes should be affordable to all countries, irrespectively of economical and climatic conditions. Outer membrane vesicles (OMVs) are bacterial-derived vesicles that can be engineered to incorporate heterologous antigens. Given the inherent adjuvanticity, such modified OMVs can be used as vaccine to induce potent immune responses against the associated protein. Here we show that OMVs engineered to incorporate peptides derived from the receptor binding motif (RBM) of the spike protein from SARS-CoV-2 elicit an effective immune response in immunized mice, resulting in the production of neutralizing antibodies. The immunity induced by the vaccine is sufficient to protect K18-hACE2 transgenic mice from intranasal challenge with SARS-CoV-2, preventing both virus replication in the lungs and the pathology associated with virus infection. Furthermore, we show that OMVs can be effectively decorated with RBM peptides derived from a different genetic variant of SARS-CoV-2, inducing a similarly potent neutralization activity in vaccinated mice. Altogether, given the convenience associated with ease of engineering, production and distribution, our results demonstrate that OMV-based SARS-CoV-2 vaccines can be a crucial addition to the vaccines currently available.

immunology↗

Effects of C-peptide replacement therapy on bone microarchitecture parameters in streptozotocin-diabetic rats.

Pathological pathways involved in the development of diabetic complications are still unclear. Several studies suggested a pathogenic role of C-peptide deficiency in vascular and neuropathic complications. However, to date, the role of C-peptide on diabetes-related bone loss has not been investigated. The objective of this study was to test the effects of a 6-week regimen of rat C-peptide infusion on bone by combining micro-CT imaging with histological testing. Twenty-three, four-month-old male Wistar rats were randomly divided into three groups: Normal control group; Sham diabetic control group; Diabetic plus C-peptide group. Diabetes was induced by injection of streptozotocin. Rat C-peptide was delivered via subcutaneously osmopumps. We assessed several trabecular microarchitectural parameters and cellular and matrix proteins in bone tissue sections. At the end of the study, both the normal control and diabetic plus C-peptide groups had a higher tibia weight than the diabetic control group (p = 0.05 and p = 0.02, respectively). C-peptide levels significantly and positively correlated with the trabecular thickness (r= 0.45, p=0.08) and negatively with structure model index (r= -0.40, p=0.09). Furthermore, it positively correlated with one of the histological assessments (i.e. PLIN1 score; p=0.02). Micro-CT evaluation showed significant inter-group differences in trabecular thickness (p=0.02), trabecular space (p = 0.05) and cross-sectional thickness (p=0.05). Diabetic plus C-peptide group showed a higher trabecular thickness (p<0.001), cross-sectional thickness (p=0.03) and a lower trabecular space (p=0.05) than the normal control group. Both the normal control and diabetic plus C-peptide groups had more Runx-2 and PLIN1 positive cells in comparison to the diabetic control group (p = 0.045 and p = 0.034). For the first time we demonstrated that the diabetic rats receiving rat C-peptide had higher quality of trabecular bone, than diabetic rats not receiving it. C-peptide could have a role in the prevention of diabetes-related bone loss.

systems biology↗