ABSTRACT
Although human antibodies elicited by severe acute respiratory distress syndrome coronavirus-2 (SARS-CoV-2) nucleocapsid (N) protein are profoundly boosted upon infection, little is known about the function of N-directed antibodies. Herein, we isolated and profiled a panel of 32 N protein-specific monoclonal antibodies (mAb) from a quick recovery coronavirus disease-19 (COVID-19) convalescent, who had dominant antibody responses to SARS-CoV-2 N protein rather than to Spike protein. The complex structure of N protein RNA binding domain with the highest binding affinity mAb nCoV396 reveals the epitopes and antigens allosteric changes. Functionally, a virus-free complement hyper-activation analysis demonstrates that nCoV396 specifically compromises N protein-induced complement hyper-activation, a risk factor for morbidity and mortality in COVID-19, thus paving the way for functional anti-N mAbs identification. One Sentence SummaryB cell profiling, structural determination, and protease activity assays identify a functional antibody to N protein.
ABSTRACT
The aim of the eight year medical education program is to cultivate high-leveled and high qualified clinical and research personnel.Constructing forensic interest group for medical students of eight year program can not only cultivate the students' English learning,innovative thinking and practice ability,which is their Achilles heel but also combine eight year medical education with forensic science teaching reform.
ABSTRACT
Severe Acute Respiratory Syndrome(SARS)is a deadly infectious disease caused by SARS Coronavirus(SARS-CoV).Inactivated SARS-CoV has been explored as a vaccine against SARS-CoV.However,safe and potent adjuvants,especially with more efficient and economical needle-free vaccination are always needed more urgently in a pandemic.The development of a safe and effective mucosal adjuvant and vaccine for prevention of emergent infectious diseases such as SARS will be an important advancement.PIKA,a stabilized derivative of Poly(I:C),was previously reported to be safe and potent as adjuvant in mouse models.In the present study,we demonstrated that the intraperitoneal and intranasal co-administration of inactivated SARS-CoV vaccine together with this improved Poly(I:C)derivative induced strong anti-SARS-CoV mucosal and systemic humoral immune responses with neutralizing activity against pseudotyped virus.Although intraperitoneal immunization of inactivated SARS-CoV vaccine alone could induce a certain level of neutralizing activity in serum as well as in mucosal sites,co-administration of inactivated SARS-CoV vaccine with PIKA as adjuvant could induce a much higher neutralizing activity.When intranasal immunization was used,PIKA was obligatorily for inducing neutralizing activity in serum as well as in mucosal sites and was correlated with both mucosal IgA and mucosal IgG response.Overall,PIKA could be a good mucosal adjuvant candidate for inactivated SARS-CoV vaccine for use in possible future pandemic.
