Fusion Protein of Rotavirus VP6 and SARS-CoV-2 Receptor Binding Domain Induces T Cell Responses.
Kirsi TamminenSuvi HeinimäkiStina GröhnVesna BlazevicPublished in: Vaccines (2021)
Vaccines based on mRNA and viral vectors are currently used in the frontline to combat the ongoing pandemic caused by the novel Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2). However, there is still an urgent need for alternative vaccine technologies inducing/boosting long-lasting and cross-reactive immunity in different populations. As a possible vaccine candidate, we employed the rotavirus VP6-protein platform to construct a fusion protein (FP) displaying receptor-binding domain (RBD) of SARS-CoV-2 spike protein (S) at the N-terminus of VP6. The recombinant baculovirus-insect cell produced VP6-RBD FP was proven antigenic in vitro and bound to the human angiotensin-converting enzyme 2 (hACE2) receptor. The FP was used to immunize BALB/c mice, and humoral- and T cell-mediated immune responses were investigated. SARS-CoV-2 RBD-specific T cells were induced at a high quantity; however, no RBD or S-specific antibodies were detected. The results suggest that conformational B cell epitopes might be buried inside the VP6, while RBD-specific T cell epitopes are available for T cell recognition after the processing and presentation of FP by the antigen-presenting cells. Further immunogenicity studies are needed to confirm these findings and to assess whether, under different experimental conditions, the VP6 platform may present SARS-CoV-2 antigens to B cells as well.
Keyphrases
- sars cov
- respiratory syndrome coronavirus
- disease virus
- binding protein
- immune response
- angiotensin converting enzyme
- angiotensin ii
- coronavirus disease
- type diabetes
- protein protein
- molecular dynamics
- dendritic cells
- toll like receptor
- oxidative stress
- cell proliferation
- mass spectrometry
- skeletal muscle
- inflammatory response
- case report
- cell cycle arrest
- cell free
- small molecule
- bone marrow
- signaling pathway
- high resolution
- cell death
- case control
- high speed
- pi k akt