ABSTRACT
Coronavirus disease 2019 (COVID-19), which is triggered by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, continues to threaten global public health. Developing a vaccine that only requires single immunization but provides long-term protection for the prevention and control of COVID-19 is important. Here, we developed an adeno-associated virus (AAV)-based vaccine expressing a stable receptor-binding domain (SRBD) protein. The vaccine requires only a single shot but provides effective neutralizing antibodies (NAbs) over 598 days in rhesus macaques (Macaca mulatta). Importantly, our results showed that the NAbs were kept in high level and long lasting against authentic wild-type SARS-CoV-2, Beta, Delta and Omicron variants using plaque reduction neutralization test. Of note, although we detected pre-existing AAV2/9 antibodies before immunization, the vaccine still induced high and effective NAbs against COVID-19 in rhesus macaques. AAV-SRBD immune serum also efficiently inhibited the binding of ACE2 with RBD in the SARS-CoV-2 B.1.1.7 (Alpha), B.1.351 (Beta), P.1/P.2 (Gamma), B.1.617.2 (Delta), B.1.617.1/3(Kappa), and C.37 (Lambda) variants. Thus, these data suggest that the vaccine has great potential to prevent the spread of SARS-CoV-2.
ABSTRACT
Objective To establish spastic cerebral palsy model of macaque by partial resection of motor cortex and explore its evaluation method.Methods Four individuals of 3-month-old macaques were divided into healthy control group and operation model group according to random number table.Partial resection of the motor cortex was carried out in operation model group,in which precentral gyrus cortex from above the right lateral cerebral fissure to the inter-hemicerebral fissure,together with the posterior-superior frontal gyrus (about 0.3 to 0.5 cm in front of the anterior median sulcus) cortex were removed with the depth of about 0.5 to 0.6 cm.After the operation,the continuous camera shooting was used to record whether left limb motor dysfunction and abnormal posture existed or not.Muscle tension was assessed by manual examination of muscle tone with reference to the modified Ashworth scale.The quantitative indexes of the two groups were detected by using the gross motor and fine motor assessment scale.9.4T magnetic resonance imaging (MRI) was used to detect the brain imaging changes.Results After operation,the macaque in the operation model group immediately showed left hemiparesis,left upper limb abnormal lifting,left lower limb paralysis,left limb claudication,and eating mainly relied on the right side of the body.After 6 weeks of operation,left limb activity of the operation model group was significantly lower than that of the healthy control group,and the gross motor scores and fine motor scores were significantly lower than those of the healthy control group(Friedman test:χ2=33.939,P<0.05;χ2=37.526,P<0.05).The macaque in the operation model group showed some symptoms that abnormal posture mainly tilted to the left for the rest,sitting in a corner of the monkey cage,left arm was put on the cage to maintain postural balance,and movement was left slightly inclined,which had simulated the typical clinical manifestations of human spastic hemiplegic cerebral palsy.Muscle tension was checked by hand,and the left limb paralysis and muscle tension decreased after operation in the model group,and the left muscle tension increased gradually after 5 weeks,and gradually increased to score 4 points and the score remained 3 after 10 weeks.Brain MRI of 3 weeks postoperatively suggested scar tissue formation after right motor cortex resection,which supported the pathological changes of the hemiplegic cerebral palsy models.Conclusions Through the partial resection of the motor cortex,the model of spastic cerebral palsy was established successfully.The results of behavioral evaluation and MRI showed that the model was consis-tent with spastic hemiplegia.
