In December 2019, viral pneumonia (Covid-19) caused by a novel beta-coronavirus (SARS-CoV-2) broke out in Wuhan, China. Some patients rapidly progressed and suffered severe acute respiratory failure and died, making it imperative to develop a safe and effective vaccine to treat and prevent severe Covid-19 pneumonia. Based on detailed analysis of the viral genome and search for potential immunogenic targets, a synthetic minigene has been engineered based on conserved domains of the viral structural proteins and a polyprotein protease. The infection of Covid-19 is mediated through binding of the Spike protein to the ACEII receptor, and the viral replication depends on molecular mechanisms of all of these viral proteins. This trial proposes to develop universal vaccine and test innovative Covid-19 minigenes engineered based on multiple viral genes, using an efficient lentiviral vector system (NHP/TYF) to express viral proteins and immune modulatory genes to modify artificial antigen presenting cells (aAPC) and to activate T cells. In this study, the safety and immune reactivity of this aAPC vaccine will be investigated.
Background: The 2019 discovered new coronavirus, SARS-CoV-2, is an enveloped positive strand single strand RNA virus. The number of SARS-CoV-2 infected people has increased rapidly and WHO has warned that the pandemic spread of Covid-19 is imminent and would have disastrous outcomes. Covid-19 could pose a serious threat to human health and the global economy. There is no vaccine available or clinically approved antiviral therapy as yet. This study aims to evaluate the safety and immune reactivity of a genetically modified aAPC universal vaccine to treat and prevent Covid-19. Objective: Primary study objectives: Injection of Covid-19/aAPC vaccine to volunteers to evaluate the safety. Secondary study objectives: To evaluate the anti- Covid-19 reactivity of the Covid-19/aAPC vaccine. Design: 1. Based on the genomic sequence of the new coronavirus SARS-CoV-2, select conserved and critical structural and protease protein domains to engineer lentiviral minigenes to express SARS-CoV-2 antigens. 2. The Covid-19/aAPC vaccine is prepared by applying lentivirus modification including immune modulatory genes and the viral minigenes, to the artificial antigen presenting cells (aAPCs). The Covid-19/aAPCs are then inactivated for proliferation and extensively safety tested. 3. The subjects receive a total of 5x10\^ 6 cells each time by subcutaneous injection at 0, 14 and 28 days. The subjects are followed-up with peripheral blood tests at 0, 14, 21, 28 and 60 days until the end of the test.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
100
The subjects will receive three injections of 5x10\^6 each Covid-19/aAPC vaccine via subcutaneous injections.
Shenzhen Geno-immune Medical Institute
Shenzhen, Guangdong, China
Frequency of vaccine events
Frequency of vaccine events such as fever, rash, and abnormal heart function.
Time frame: Measured from Day 0 through Day 28
Frequency of serious vaccine events
Frequency of serious vaccine events
Time frame: Measured from Day 0 through Day 28
Proportion of subjects with positive T cell response
Time frame: 14 and 28 days after randomization
28-day mortality
Number of deaths during study follow-up
Time frame: Measured from Day 0 through Day 28
Duration of mechanical ventilation if applicable
Duration of mechanical ventilation use in days. Multiple mechanical ventilation durations are summed up
Time frame: Measured from Day 0 through Day 28
Proportion of patients in each category of the 7-point scale
Proportion of patients in each category of the 7-point scale, the 7-category ordinal scale that ranges from 1 (discharged with normal activity) to 7 (death)
Time frame: 7,14 and 28 days after randomization
Proportion of patients with normalized inflammation factors
Proportion of patients with different inflammation factors in normalization range
Time frame: 7 and 14 days after randomization
Clinical improvement based on the 7-point scale if applicable
A decline of 2 points on the 7-point scale from admission means better outcome. The 7-category ordinal scale that ranges from 1 (discharged with normal activity) to 7 (death)
Time frame: 28 days after randomization
Lower Murray lung injury score if applicable
Murray lung injury score decrease more than one point means better outcome. The Murray scoring system range from 0 to 4 according to the severity of the condition
Time frame: 7 days after randomization
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