Recombinant chimpanzee adenovirus AdC7 expressing dimeric tandem-repeat RBD of SARS-CoV-2 spike protein protects mice against COVID-19

A safe and effective vaccine is urgently needed to control the unprecedented COVID-19 pandemic. Four adenovirus vectored vaccines expressing spike (S) protein have advanced into phase 3 trials, with three approved for use. Here, we generated several recombinant chimpanzee adenovirus (AdC7) vaccines expressing S, receptor-binding domain (RBD) or dimeric tandem-repeat RBD (RBD-tr2). We found vaccination via either intramuscular or intranasal route was highly immunogenic in mice to elicit both humoral and cellular (Th1-based) immune responses. AdC7-RBD-tr2 showed higher antibody responses compared with both AdC7-S and AdC7-RBD. Intranasal administration of AdC7-RBD-tr2 additionally induced mucosal immunity with neutralizing activity in bronchoalveolar lavage fluid. Either single-dose or two-dose mucosal administration of AdC7-RBD-tr2 protected mice against SARS-CoV-2 challenge, with undetectable subgenomic RNA in lung and relieved lung injury. These results support AdC7-RBD-tr2 as a promising COVID-19 vaccine candidate.

Donor-Derived CD123-Targeted CAR T Cell Serves as a RIC Regimen for Haploidentical Transplantation in a Patient With FUS-ERG+ AML.

Background: Allogeneic hematopoietic stem cell transplantation (allo-HSCT) following chemotherapy is part of standard treatment protocol for patients with acute myeloid leukemia (AML). FUS-ERG+ AML is rare but has an extremely poor prognosis even with allo-HSCT in remission, possibly due to its a leukemia stem cell (LSC)-driven disease resulting in chemotherapy resistance and a novel therapy is urgently required. It has been reported that FUS-ERG-positive AML expresses CD123, a marker of LSC, in some cases. CD123-targeted CAR T cell (CART123) is promising immunotherapy, but how to improve the complete remission (CR) rate and rescue potential hematopoietic toxicity still need to explore. Case Presentation: We used donor-derived CART123 as part of conditioning regimen for haploidentical HSCT (haplo-HSCT) in a patient with FUS-ERG+ AML who relapsed after allogeneic transplantation within 3 months, resists to multi-agent chemotherapy and donor lymphocyte infusion (DLI) and remained non-remission, aiming to reduce these chemotherapy-resistant blasts and rescue potential hematopoietic toxicity. The blasts in BM were reduced within 2 weeks and coincided with CAR copies expansion after CART123 infusion. The patient achieved full donor chimerism, CR with incomplete blood count recovery, and myeloid implantation. Conclusion: Our results hints that CART123 reduces the chemotherapy-resistant AML blasts for FUS-ERG+ AML without affecting the full donor chimerism and myeloid implantation.

Clinical efficacy of recombinant activated factor Ⅶ a for 16 hematonosis with moderate or severe bleeding / 中华血液学杂志

Objective@#To analyze the efficacy of recombinant activated factor Ⅶ a (rF Ⅶ a) on hematonosis with moderate or severe bleeding signs.@*Methods@#Of total 16 cases with rF Ⅶ a treatment from May 2013 to May 2016, 8 cases received allogeneic hematopoietic stem cells transplantation (allo-HSCT) and the other were non-transplantation patients. In two groups, there was no significant difference on rF Ⅶ a usage and dosage. 15 patients with acute graft-versus-host disease (aGVHD) after allo-HSCT were control group (without rF Ⅶ a) .@*Results@#①The total response rate was 75.0% (6/8) in non-transplantation group and 37.5% (3/8) in transplantation group, respectively. Median interval for hemorrhage stop was 38.5 hours in non-transplantation group and 63.0 hours in transplantation group. The median overall survival (OS) was 201.0 and 29.0 days for non-transplantation group and transplantation group, respectively, and the OS rate was 50.0% (4/8) and 25.0% (2/8) , respectively. The bleeding-related mortality rate was 50.0% (2/4) and 83.3% (5/6) , respectively. ②Of the 16 cases, 9 showed response to rF Ⅶ a treatment and the other 7 cases’bleeding signs did not alleviate. The median OS was 268.0 in 9 cases with response and 24.0 days in 7 cases without response, respectively. ③In patients with intestinal aGVHD complicated with intestinal hemorrhage, the median OS of observation group (n=6) and control group (n=15) were 25.5 days and 20.0 days, respectively.@*Conclusion@#Patients with hematological diseases, especially patients after allo-HSCT, had high bleeding-related mortality, and rFⅦa therapy had a obvious hemostatic efficacy. The survival rate of patients with response was higher than that of cases without response. The causes of poor hemostasis efficacy of rF Ⅶ a therapy were associated with unsatisfactory control of complications in patients with intestinal bleeding after allo-HSCT.