ABSTRACT
Breakthrough infections by SARS-CoV-2 variants pose a global challenge to pandemic control, and the development of more effective vaccines of broad- spectrum protection is needed. In this study, we constructed pVAX1-based plasmids encoding heterodimeric receptor-binding domain (RBD) chimera of SARS-CoV and SARS-CoV-2 Omicron BA.1 (RBDSARS/BA1), SARS-CoV and SARS- CoV-2 Beta (RBDSARS/Beta), or Omicron BA.1 and Beta (RBDBA1/Beta) in secreted form. When i.m. injected in mice, RBDSARS/BA1 and RBDSARS/Beta encoding plasmids (pAD1002 and pAD131, respectively) were by far more immunogenic than RBDBA1/Beta plasmid (pAD1003). Dissolvable microneedle array patches (MAP) laden with these DNA plasmids were fabricated. All 3 resulting MAP-based vaccine candidates, namely MAP-1002, MAP1003 and MAP-131, were comparable to i.m. inoculated plasmids with electroporation assistance in eliciting strong and durable IgG responses in BALB/c and C57BL/6 mice as well as rabbits, while MAP-1002 was comparatively the most immunogenic. More importantly, MAP-1002 significantly outperformed inactivated SARS-CoV-2 virus vaccine in inducing RBD-specific IFN-g+ T cells. Moreover, MAP-1002 antisera effectively neutralized pseudo- viruses displaying spike proteins of SARS-CoV, prototype SARS-CoV-2 or Beta, Delta, Omicron BA1, BA2 and BA4/5 variants. Collectively, MAP-based DNA constructs encoding chimeric RBDs of SARS-CoV and SARS-CoV-2 variants, as represented by MAP-1002, are potential COVID-19 vaccine candidates worthy further translational study.
Subject(s)
COVID-19 , Severe Acute Respiratory SyndromeABSTRACT
Strict lockdowns were implemented in China to fight Coronavirus Disease 2019 (COVID‐19). We explored the nighttime light (NTL) of China’s four cities in five stages of COVID‐19 including case free period, newly appeared period, rising period, outbreak period, and stationary period. Using six categories of points of interest (POIs) data (“company”, “recreation”, “healthcare”, “residence”, “shopping”, and “traffic facility”) and random forest models, we found that dimming light of four cities is associated with the epidemic development and human activity changes. When confirmed cases appeared, healthcare associated NTL radiance increased rapidly in Wuhan and Guangzhou, but decreased in the fourth and fifth stages. Companies in all cities were resuscitated in the fifth stage, while companies in Guangzhou was resuscitated in the fourth stage. Shopping related NTL radiance in Wuhan increased quickly in the fifth stage which indicated some resuscitation. In addition, compared to gross domestic product (GDP), the trend in electric power consumption (EPC) was consistent with the trend in NTL radiance. The above findings contribute to the making of control policies for COVID‐19 as well as other infectious diseases. Key Points Dimming light during COVID‐19 lockdown observed by satellite coincides with the stage of epidemic development Changes in six categories of human activity can be considerably explained by nighttime light changes (around 52%) GDP (or electric power consumption) has a consistent trend with the nighttime light radiance
ABSTRACT
The COVID-19 disease caused by infection with SARS-CoV-2 and its variants is devastating to the global public health and economy. To date, over a hundred COVID-19 vaccines are known to be under development and the few that have been approved to fight the disease are using the spike protein as the primary target antigen. Although virus neutralizing epitopes are mainly located within the RBD of the spike protein, the presence of T cell epitopes, particularly the CTL epitopes that are likely to be needed for killing infected cells, has received comparatively little attention. In this study, we predicted several potential T cell epitopes with web-based analytic tools, and narrowed them down from several potential MHC I and MHC II epitopes by ELIspot and cytolytic assays to a conserved MHC I epitope. The epitope is highly conserved in current viral variants and compatible with presentation by most HLA alleles worldwide. In conclusion, we identified a CTL epitope suitable for evaluating the CD8+ T cell-mediated cellular response and potentially for addition into future COVID-19 vaccine candidates to maximize CTL responses against SARS-CoV-2.
Subject(s)
COVID-19ABSTRACT
The COVID-19 disease caused by infection with SARS-CoV-2 and its variants is devastating to the global public health and economy. To date, over a hundred COVID-19 vaccines are known to be under development and the few that have been approved to fight the disease are using the spike protein as the primary target antigen. Although virus neutralizing epitopes are mainly located within the RBD of the spike protein, the presence of T cell epitopes, particularly the CTL epitopes that are likely to be needed for killing infected cells, has received comparatively little attention. In this study, we predicted several potential T cell epitopes with web-based analytic tools, and narrowed them down from several potential MHC‑I and MHC‑II epitopes by ELIspot and cytolytic assays to a conserved MHC‑I epitope. The epitope is highly conserved in current viral variants and compatible with presentation by most HLA alleles worldwide. In conclusion, we identified a CTL epitope suitable for evaluating the CD8+ T cell-mediated cellular response and potentially for addition into future COVID-19 vaccine candidates to maximize CTL responses against SARS-CoV-2.
Subject(s)
COVID-19 , Hereditary Angioedema Types I and IIABSTRACT
The pandemic of SARS-CoV-2 coronavirus disease-2019 (COVID-19) caused by SARS-COV-2 continues to ravage many countries in the world. Mpro is an indispensable protein for viral translation in SARS-CoV-2 and a potential target in high-specificity anti-SARS-CoV-2 drug screening. In this study, to explore potential drugs for treating COVID-19, we elucidated the structure of SARS-CoV-2 Mpro and explored the interaction between Mpro and GC376, an antiviral drug used to treat a range of coronaviruses in Feline via inhibiting Mpro. The availability and safety of GC376 were proved by biochemical and cell experiments in vitro. We determined the structure of an important protein, Mpro, in SARS-CoV-2, and revealed the interaction of GC376 with the viral substrate and inhibition of the catalytic site of SARS-CoV-2 Mpro.
Subject(s)
Coronavirus Infections , COVID-19ABSTRACT
Since the outbreak of COVID-19 in China at the end of 2019, the world has experienced a large-scale epidemic caused by the SARS-CoV-2. Epidemiological and clinical course of COVID-19 patients have been reported, but there have been few analyses about the characteristics, predictive risk factors and outcomes of critical patients. In this single-center retrospective case-control study, 90 adult inpatients hospitalized at Tongji Hospital (Wuhan, China) were included. Demographic, clinical, laboratory test and treatment data were obtained and compared between critical and non-critical patients. We found that compared with non-critical patients, the critical patients had higher SOFA score and qSOFA scores. Critical patients had lower lymphocyte and platelet count, elevated D-dimer, decreased fibrinogen, and elevated high-sensitivity C-reactive protein (hsCRP) and interleukin-6(IL-6). More critical patients received treatment including antibiotics, anticoagulation, corticosteroid and oxygen therapy than non-critical ones. Multivariable regression showed higher qSOFA score and elevation of IL-6 were related to critical patients. Antibiotic usage and anticoagulation were associated with decreased in-hospital mortality. And critical grouping contributed greatly to in-hospital death. Critical COVID-19 patients have a more severe clinical cours. qSOFA score and elevation of IL-6 are risk factors for critical condition. Non-critical grouping, positive antibiotic application and anticoagulation may be beneficial for patient survival.