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 sufferedsevere acute respiratory failure and died, making it imperative to develop a safe andeffective vaccine to treat and prevent severe Covid-19 pneumonia. Based on detailedanalysis of the viral genome and search for potential immunogenic targets, a syntheticminigene has been engineered based on conserved domains of the viral structural proteinsand a polyprotein protease. The infection of Covid-19 is mediated through binding of theSpike protein to the ACEII receptor, and the viral replication depends on molecularmechanisms of all of these viral proteins. This trial proposes to develop universalvaccine and test innovative Covid-19 minigenes engineered based on multiple viral genes,using an efficient lentiviral vector system (NHP/TYF) to express viral proteins andimmune modulatory genes to modify artificial antigen presenting cells (aAPC) and toactivate T cells. In this study, the safety and immune reactivity of this aAPC vaccinewill 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.
Biological: Pathogen-specific aAPC
The subjects will receive three injections of 5x10^6 each Covid-19/aAPC vaccine via
subcutaneous injections.
Inclusion Criteria:
- Healthy and Covid-19-positive volunteers
- The interval between the onset of symptoms and randomized is within 7 days in
Covid-19 patients. The onset of symptoms is mainly based on fever. If there is no
fever, cough or other related symptoms can be used;
- White blood cells ≥ 3,500/μl, lymphocytes ≥ 750/μl;
- Human immunodeficiency virus (HIV), hepatitis B virus (HBV), hepatitis C virus (HCV)
or tuberculosis (TB) test negative;
- Sign the Informed Consent voluntarily;
Exclusion Criteria:
- Subject with active HCV, HBV or HIV infection.
- Subject is albumin-intolerant.
- Subject with life expectancy less than 4 weeks.
- Subject participated in other investigational vaccine therapies within the past 60
days.
- Subject with positive pregnancy test result.
- Researchers consider unsuitable.
Shenzhen Geno-immune Medical Institute
Shenzhen, Guangdong, China
Investigator: Lung-Ji Chang
Contact: 86-755-86725195
c@szgimi.org
Lung-Ji Chang
+86(755)8672 5195
c@szgimi.org
Lung-Ji Chang, Principal Investigator
Shenzhen Geno-Immune Medical Institute