NCT04276896

Immunity and Safety of Covid-19 Synthetic Minigene Vaccine

Phase I/II Multicenter Trial of Lentiviral Minigene Vaccine (LV-SMENP) of Covid-19 Coronavirus

• Status: Unknown
• Phase: Phase 1 / Phase 2
• Study type: Interventional
• Enrollment: 100 (estimated)
• Sponsor: Shenzhen Geno-Immune Medical Institute · Academic / Other
• Sex: All
• Age: 6 Months – 80 Years
• Healthy volunteers: Not accepted

Summary

In December 2019, viral pneumonia caused by a novel beta-coronavirus (Covid-19) 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 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 dendritic cells (DCs) and to activate T cells. In this study, the safety and efficacy of this LV vaccine (LV-SMENP) will be investigated.

Detailed description

Background: The 2019 discovered new coronavirus, Covid-19, is an enveloped positive strand single strand RNA virus. The number of Covid-19 infected people has increased rapidly and WHO has warned that the spread of Covid-19 may soon become pandemic and have disastrous outcomes. Covid-19 could pose a serious threat to human health and global economy. There is no vaccine available or clinically approved antiviral therapy as yet. This study aims to evaluate the safety and efficacy of treating Covid-19 infections with a novel lentiviral based DC and T cell vaccines. Objective: Primary study objectives: Injection and infusion of LV-SMENP DC and antigen-specific cytotoxic T cell vaccines to healthy volunteers and Covid-19 infected patients to evaluate the safety. Secondary study objectives: To evaluate the anti- Covid-19 efficacy of the LV-SMENP DC and antigen-specific cytotoxic T cell vaccines. Design: 1. Based on the genomic sequence of the new coronavirus Covid-19, select conserved and critical structural and protease protein domains to engineer lentiviral SMENP minigenes to express Covid-19 antigens. 2. LV-SMENP-DC vaccine is made by modifying DC with lentivirus vectors expressing Covid-19 minigene SMENP and immune modulatory genes. CTLs will be activated by LV-DC presenting Covid-19 specific antigens. 3. LV-DC vaccine and antigen-specific CTLs are prepared in 7\~21 days. Subject will receive total 5x10\^6 cells of LV-DC vaccine and 1x10\^8 antigen-specific CTLs via sub-cutaneous injection and IV infusion, respectively. Patients are followed weekly for one month after the infusion, monthly for 3 months, and then every 3 months until the trial ends.

Conditions

• Pathogen Infection Covid-19 Infection

Interventions

Type	Name	Description
BIOLOGICAL	Injection and infusion of LV-SMENP-DC vaccine and antigen-specific CTLs	Patients will receive approximately 5x10\^6 LV-DC vaccine and 1x10\^8 CTLs via sub-cutaneous injections and iv infusions, respectively.

Timeline

• Start date: 2020-03-24
• Primary completion: 2023-07-31
• Completion: 2024-12-31
• First posted: 2020-02-19
• Last updated: 2020-03-19

Locations

3 sites across 1 country: China