Prime-boost vaccinations with two serologically distinct chimpanzee adenovirus vectors expressing SARS-CoV-2 spike or nucleocapsid tested in a hamster COVID-19 model

Two serologically distinct replication-defective chimpanzee-origin adenovirus (Ad) vectors (AdC) called AdC6 and AdC7 expressing the spike (S) or nucleocapsid (N) proteins of an early SARS-CoV-2 isolate were tested individually or as a mixture in a hamster COVID-19 challenge model. The N protein, which was expressed as a fusion protein within herpes simplex virus glycoprotein D (gD) stimulated antibodies and CD8+ T cells. The S protein expressing AdC (AdC-S) vectors induced antibodies including those with neutralizing activity that in part cross-reacted with viral variants. Hamsters vaccinated with the AdC-S vectors were protected against serious disease and showed accelerated recovery upon SARS-CoV-2 challenge. Protection was enhanced if AdC-S vectors were given together with the AdC vaccines that expressed the gDN fusion protein (AdC-gDN). In contrast hamsters that just received the AdC-gDN vaccines showed only marginal lessening of symptoms compared to control animals. These results indicate that immune response to the N protein that is less variable that the S protein may potentiate and prolong protection achieved by the currently used genetic COVID-19 vaccines.

Pre-clinical testing of two serologically distinct chimpanzee-origin adenovirus vectors expressing spike of SARS-CoV-2

Two serologically distinct chimpanzee-origin, replication-defective adenovirus (AdC) vectors expressing the spike (S) protein of an early severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) isolate were generated and tested for induction of antibodies in young and aged mice. Both vectors induced S protein-specific antibodies including neutralizing antibodies. Levels of antibodies increased after a boost. The effectiveness of the boost depended on vector dose and timing between the two immunizations. Using two heterologous AdC vectors was more effective than vaccinating with the same vector repeatedly. Antibodies partially crossreacted between different S protein variants. Cross-reactivity increased after booster immunization with vectors carrying the same S gene, expression of two different S proteins by the AdC vectors used for the prime and the boost did not selectively increase responses against the variants.

Retrospective analysis of external quality assessment results for hemoglobin measurement in Guangxi Province during 2012 to 2016 / 临床检验杂志

Objective To evaluate the detection competence of HbA2 and HbF in Guangxi medical laboratories.Methods The external quality assessment(EQA) of HbA2 and HbF was conducted twice a year and five samples was detected each time during 2012 to 2016.The laboratories participated in EQA completed the samples' detection and submitted the detection results at specified time according to the requirements of EQA.The distribution of each detection system,the qualification rate of each laboratory,the variation degrees of each detection system and each detection method,and the variations of results for different levels of quality control(QC) materials during 5 years were analyzed based on the returned results.Results The application of high performance liquid chromatography (HPLC) and capillary electrophoresis(CE) increased year by year and their usage rates in 2016 reached up to 46.1％ (82/178) and 18.0％ (32/178),respectively.The qualification rates of HbA2 and HbF increased from 51.5％ (34/66) and 60.6％ (40/66) in 2012 to 93.3％ (166/178) and 92.1％ (164/178) in 2016,respectively.The average coefficient of variation(CV) of each detection system decreased year by year.There were good CVs for the results of high,medium and low levels of HbA2 QC materials detected by the Bio-Rad Variant Ⅱ and Sebia CAPILLARYS 2 systems,and they were less than 6.0％.HPLC and CE could quantitatively detect the HbA2 and HbF levels,and their total detection competence was superior to that of agarose gel electrophoresis.Conclusion EQA can assess the abihty of one laboratory detecting HbA2 and HbF,and quantitatively analyze the levels of HbA2 and HbF,which may provide the quality assurance and data support for the screening and prevention of thalassemia.

Seroprevalence of neutralizing antibodies to human adenovirus type 5, human adenovirus type 26 and chimpanzee adenovirus type 68 in patients with chronic hepatitis B and patients with primary liver cancer / 中国病理生理杂志

[ ABSTRACT] AIM: To investigate the seroprevalence of neutralizing antibodies to human adenovirus type 5 (AdHu5) , human adenovirus type 26 (AdHu26) and chimpanzee adenovirus type 68 (AdC68) in the patients with chro-nic hepatitis B ( CHB) and the patients with primary liver cancer ( PLC) , and to provide guidance for developing safe and effective biotherapy vectors against CHB and PLC.METHODS:The blood samples from 196 patients with CHB and 193 patients with PLC were examined to assess the presence of neutralizing antibodies against AdHu5, AdHu26 and AdC68 by adenovirus neutralization assays.RESULTS:The seroprevalence rates of neutralizing antibodies to AdHu5, AdHu26 and AdC68 in the CHB patients were 84.7%, 58.2%and 39.8%, respectively.Among the patients with PLC, the prevalence rates of neutralizing antibodies were as follows:AdHu5, 75.1%;AdHu26, 66.8%;AdC68, 32.1%.CONCLUSION:The prevalence rates and titers of neutralizing antibodies against AdC68 were the lowest among the 3 adenoviruses.There-fore, AdC68 serves as more suitable biological therapy vectors for CHB and PLC than AdHu5 and AdHu26.

The expression and significance of IGF-1R in nasal polyp and its relationship with allergic rhinitis / 临床耳鼻咽喉头颈外科杂志

OBJECTIVE@#To study the expression of insulin-like growth factor-1 receptor(IGF-1R) in nasal polyps and its relationship with allergic rhinitis.@*METHOD@#The mRNA and protein expression of IGF-1R in 40 cases (20 cases with allergic rhinitis and 20 cases without) nasal polyps tissue (the CRSWNP group) and 20 middle turbinate tissue samples (the control group) were examined by fluorescence quantitative polymerase chain reaction (FQ-PCR) and immunohistochemistry.@*RESULT@#The positive staining rate of IGF-1R protein of nasal polyps tissue is 70.8% and that of control is 12.3%, the expression of IGF-1R mRNA of nasal polyp is 0.748 +/- 0.111,which is significant higher than that of the control group is 0.107 +/- 0.208 (P < 0.01). No significant difference of the expression of IGF-1R mRNA between with and without allergic rhinitis cases and between with and without endoscopy sinus surgery history cases in the CRSWNP group.@*CONCLUSION@#The overexpression of IGF-1R maybe play important roles in the formation of nasal polyp. Hypersensitivity reaction type I mediated by IgE has no contribution to the overexpression of the IGF-1R.

Analysis for the correlation between skin prick test and clinical characteristics in patients with chronic sinusitis with nasal polyps / 中国耳鼻咽喉头颈外科

OBJECTIVE To investigate the relationship between the skin prick test and clinical characteristics in patients with chronic sinusitis with nasal polyps(CRSwNP).METHODS Sixty cases with CRSwNP and 40 control samples underwent skin prick test with standardized allergens provided by AllergoPhamar Company,the results and their clinical characteristics are analyzed.RESULTS The positive rate of skin prick test was 81.7% and 17.5% in CRSwNP group and control group respectively(?2 =40.104,?

Changes and correlation between nuclear factor-?B expression and water content in cerebral tissue after experimental intracerebral hemorrhage / 临床神经病学杂志

Objective To investigate the changes and correlation between nuclear factor-?B (NF-?B) expression and brain water content (BWC) in perihematoma after experimental intracerebral hemorrhage (ICH) in rats. Methods Experimental ICH models of rat were made by injecting autologous blood using stereotaxic method. The expression of NF-?B in cerebral tissues was detected by immunohistochemistry technique. At the due time, BWC was measurement by day-wet method.Results NF-?B expression increased obviously at 6 h and peaked at 48 h in ICH group(P