ABSTRACT
Remarkable progress has been made in developing intramuscular vaccines against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2); however, they are limited with respect to eliciting local immunity in the respiratory tract, which is the primary infection site for SARS-CoV-2. To overcome the limitations of intramuscular vaccines, we constructed a nasal vaccine candidate based on an influenza vector by inserting a gene encoding the receptor-binding domain (RBD) of the spike protein of SARS-CoV-2, named CA4-dNS1-nCoV-RBD (dNS1-RBD). A preclinical study showed that in hamsters challenged 1 day and 7 days after single-dose vaccination or 6 months after booster vaccination, dNS1-RBD largely mitigated lung pathology, with no loss of body weight, caused by either the prototype-like strain or beta variant of SARS-CoV-2. Lasted data showed that the animals could be well protected against beta variant challenge 9 months after vaccination. Notably, the weight loss and lung pathological changes of hamsters could still be significantly reduced when the hamster was vaccinated 24 h after challenge. Moreover, such cellular immunity is relatively unimpaired for the most concerning SARS-CoV-2 variants. The protective immune mechanism of dNS1-RBD could be attributed to the innate immune response in the nasal epithelium, local RBD-specific T cell response in the lung, and RBD-specific IgA and IgG response. Thus, this study demonstrates that the intranasally delivered dNS1-RBD vaccine candidate may offer an important addition to fight against the ongoing COVID-19 pandemic, compensating limitations of current intramuscular vaccines, particularly at the start of an outbreak.
ABSTRACT
We developed the monoclonal antibodies against nucleoprotein (NP) of Newcastle disease virus (NDV),and established a double antibody sandwich ELISA method for quantitative determination of NP antigen of NDV (NDV NP ELISA).The recombination NP protein derived from strain F48E9 of NDV were prepared and used to immunize BLAB/c mice.The mouse splenic cells from immunized mice were fused with SP2/0 cells to generate monoclonal antibodies (mAb).The NDV NP specific mAbs were paired to establish a double antibody sandwich ELISA method.The performance of the NDV NP ELISA was evaluated,including specificity,sensitivity,precision,accuracy and linearity.The correlation between the ELISA and PFU virus titer was analyzed by regression analysis method.Two monoclonal antibodies 3C10 and 4E7 were selected to establish double antibody sandwich ELISA for NP antigen of NDV.The linearity and performance of the NDV NP ELISA was characterized.The detection linearity fell in the range of 0.015-0.250 μg/mL (R2 =0.997 4).The detection limit of the assay was 0.015 μg/mL.The recovery was between 88.4％ and 106.01％;the variation coefficient was below 3.4％.In testing of 50 NDV virus samples,this assay performed well and correlated comparably with PFU virus titer (R2 =0.920 9).The NDV NP ELISA for quantitative detection of NDV is a reliable quantifiable assay for detection of NDV NP protein;it provides a new approach for rapid and quantitative detection of Newcastle disease virus.
ABSTRACT
OBJECTIVE@#To investigate the feasibility of salvage surgery of thyroid carcinoma in advanced stage with common carotid artery involvement.@*METHODS@#Reviewed 4 cases of advanced-stage thyroid carcinoma treated in the Department of Otolaryngology, West China hospital from July 2006 to September 2009. CT revealed that the common carotid artery entrapped in the tumor without obvious anatomical space. 2 cases were proved to be low-differentiated squamous carcinoma pathologically and the rest 2 cases were papillary carcinoma. Total thyroidectomy, total laryngectomy and bilateral neck dissection were performed in 3 cases while in one case, total thyroidectomy, bilateral neck dissection and partial tracheal resection being performed. Adjacent prepared cervico-pectoral flap was used to reconstruct the defect of cervico-thoracic trachea. Rupture of common carotid artery in one case took place and was repaired by mere suture. One case of low differentiated squamous carcinoma was given postoperative chemotherapy and radiotherapy while the rest 3 cases given no adjuvant chemotherapy and radiotherapy. The follow-up time lasted from half a year to 2 years.@*RESULTS@#Half a year postoperatively, the low-differentiated squamous carcinoma patient not receiving postoperative chemoradiotherapy suffered from lumber spinal metastasis, one year after operation he was still alive and half a year later lost follow-up, the other 3 patients were alive from half a year to 2 years postoperatively without any obvious clue of recurrence or remote metastasis.@*CONCLUSION@#Salvage surgery is still feasible in thyroid carcinoma in advanced stage with common carotid artery involvement. The larynx and trachea should be kept intact as possible but the reconstruction of the trachea defect is recommended to be less prior in the situation when carotid artery is involved in.
