Safety and Immunity of Covid-19 aAPC Vaccine

Study Overview
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Brief Summary
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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.

Detailed Description
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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: 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. 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. 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.

Official Title
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Safety and Immunity Evaluation of A Covid-19 Coronavirus Artificial Antigen Presenting Cell Vaccine

Conditions
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Treat and Prevent Covid-19 Infection

Intervention / Treatment
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* Biological: Pathogen-specific aAPC


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 6 Months
Maximum Age: 80 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Injection of Covid-19/aAPC vaccine<br> | Biological: Pathogen-specific aAPC<br>* The subjects will receive three injections of 5x10^6 each Covid-19/aAPC vaccine via subcutaneous injections.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Frequency of vaccine events | Frequency of vaccine events such as fever, rash, and abnormal heart function. | Measured from Day 0 through Day 28 | 
| Frequency of serious vaccine events | Frequency of serious vaccine events | Measured from Day 0 through Day 28 | 
| Proportion of subjects with positive T cell response |  | 14 and 28 days after randomization | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 28-day mortality | Number of deaths during study follow-up | 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 | 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) | 7,14 and 28 days after randomization | 
| Proportion of patients with normalized inflammation factors | Proportion of patients with different inflammation factors in normalization range | 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) | 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 | 7 days after randomization | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Lentiviral vector, Covid-19/aAPC vaccine