Safety and Immunity of Covid-19 aAPC Vaccine

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

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.

Study Overview

• Status: Recruiting
• Conditions: Treat and Prevent Covid-19 Infection
• Intervention / Treatment: Biological: Pathogen-specific aAPC

Detailed Description

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
• Enrollment (Anticipated): 100
• Phase: Phase 1

Contacts and Locations

• Study Contact: Name: Lung-Ji Chang; Phone Number: +86(755)8672 5195; Email: c@szgimi.org

Study Locations

• China
  • Guangdong
    • Shenzhen, Guangdong, China, 518000
      • Recruiting
      • Shenzhen Geno-immune Medical Institute
      • Contact: Lung-Ji Chang; Phone Number: 86-755-86725195; Email: c@szgimi.org

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 6 months to 80 years (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

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

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Shenzhen Geno-Immune Medical Institute
• Collaborators: Shenzhen Second People's Hospital; Shenzhen Third People's Hospital

Study record dates

Study Major Dates

• Study Start (Actual): February 15, 2020
• Primary Completion (Anticipated): July 31, 2023
• Study Completion (Anticipated): December 31, 2024

Study Registration Dates

• First Submitted: March 5, 2020
• First Submitted That Met QC Criteria: March 6, 2020
• First Posted (Actual): March 9, 2020

Study Record Updates

• Last Update Posted (Actual): March 9, 2020
• Last Update Submitted That Met QC Criteria: March 6, 2020
• Last Verified: March 1, 2020

More Information

Terms related to this study

• Keywords: Lentiviral vector, Covid-19/aAPC vaccine
• Additional Relevant MeSH Terms: Coronavirus Infections; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Virus Diseases; Infections; Respiratory Tract Infections; Respiratory Tract Diseases; Pneumonia, Viral; Pneumonia; Lung Diseases; COVID-19
• Other Study ID Numbers: GIMI-IRB-20002

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No