ABSTRACT
The COVID-19 pandemic, caused by the SARS-CoV-2 virus and its variants, has posed unprecedented challenges worldwide. Existing vaccines have limited effectiveness against SARS-CoV-2 variants. Therefore, novel vaccines to match mutated viral lineages by providing long-term protective immunity are urgently needed. We designed a recombinant adeno-associated virus 5 (rAAV5)-based vaccine (rAAV-COVID-19) by using the SARS-CoV-2 spike protein receptor binding domain (RBD-plus) sequence with both single-stranded (ssAAV5) and self-complementary (scAAV5) delivery vectors and found that it provides excellent protection from SARS-CoV-2 infection. A single-dose vaccination in mice induced a robust immune response; induced neutralizing antibody (NA) titers were maintained at a peak level of over 1:1024 more than a year post-injection and were accompanied by functional T-cell responses. Importantly, both ssAAV- and scAAV-based RBD-plus vaccines produced high levels of serum NAs against the circulating SARS-CoV-2 variants, including Alpha, Beta, Gamma and Delta. A SARS-CoV-2 virus challenge showed that the ssAAV5-RBD-plus vaccine protected both young and old mice from SARS-CoV-2 infection in the upper and lower respiratory tracts. Whole genome sequencing demonstrated that AAV vector DNA sequences were not found in the genomes of vaccinated mice one year after vaccination, demonstrating vaccine safety. These results suggest that the rAAV5-based vaccine is safe and effective against SARS-CoV-2 and several variants as it provides long-term protective immunity. This novel vaccine has a significant potential for development into a human prophylactic vaccination to help end the global pandemic.
Subject(s)
COVID-19 , Parvovirinae , Animals , Humans , Mice , SARS-CoV-2/genetics , COVID-19/prevention & control , Pandemics , Vaccines, Synthetic/genetics , Spike Glycoprotein, Coronavirus/genetics , Antibodies, Neutralizing , Antibodies, ViralABSTRACT
BACKGROUND: To determine the diagnostic value of hematologic markers for coronavirus disease 2019 (COVID-19) and explore their relationship with disease severity. METHODS: Subjects included 190 COVID-19 patients, 190 healthy subjects, and 105 influenza pneumonia (IP) patients. COVID-19 patients were divided into the ARDS and non-ARDS groups. Routine blood examination, biochemistry indicator, days in hospital, body temperature, pneumonia severity index (PSI), CURB-65, and MuLBSTA were recorded. Correlations between variables were assessed using Spearman's correlation analysis. Receiver operating characteristic (ROC) curves were used to study the accuracy of the various diagnostic tests. RESULTS: Compared with healthy subjects, COVID-19 patients had lower white blood cell (WBC), lymphocyte, platelet, and hemoglobin levels; higher percentages of neutrophils and monocytes; lower percentages of lymphocytes and higher neutrophil-to-lymphocyte ratio (NLR), monocyte-to-lymphocyte ratio (MLR), and platelet-to-lymphocyte ratio (PLR) values (P < .05). COVID-19 patients had higher WBC and neutrophil levels and lower percentages of lymphocytes compared to IP (P < .05). ROC curve analysis revealed that MLR had a high diagnostic value in differentiating COVID-19 patients from healthy subjects, but not from IP patients. NLR showed significant positive correlations with PSI, CURB-65, and MuLBSTA. Lymphocyte count was lower in the ARDS group and yielded a higher diagnostic value than the other variables. CONCLUSIONS: Monocyte-to-lymphocyte ratio showed an acceptable efficiency to separate COVID-19 patients from healthy subjects, but failed to rule out IP patients. NLR may be a reliable marker to evaluate the disease severity of COVID-19. Lymphocyte count may be useful to establish the early diagnosis of ARDS in the COVID-19 patients.