Development of Zika viral pseudoinfectious virus as Zika vaccine candidate

Executive Summary of Predicate SBIR/STTR Phase I Grant and Team TenGen Biomedical Co. and Howard University received an STTR Phase I grant (5R41AI129119-02) from the National Institute of Allergy and Infectious Diseases (NIAID) in 2017. The overall objective of our predicate STTR Phase I grant is to develop a safe, effective, and affordable Zika vaccine based on the novel concept of the third generation of flavivirus vaccine. Zika virus (ZIKV) epidemics and the association of ZIKV infection with Guillain–Barré syndrome, and congenital disabilities, including microcephaly, led the World Health Organization to declare ZIKV a “Public Health Emergency of International Concern” in 2016. Therefore, an effective Zika vaccine is urgently needed. The project proposed four specific aims:1. Construction of subgenomic replicon for ZIKV,2. Development of stable packaging cell lines providing ZIKV structural protein C in trans.3. Harvest of ZIKV PIVs from infected packaging cell line and analyzing the stability of the packaging celllines and PIV during passages,4. Preliminary analysis of the safety and immunogenicity of the proposed vaccine in mice. In the past two years, we have made 8 significant achievements forward the specific aims:1. Generation of Infectious cDNA Clones of Wildtype and Mutant Zika Virus2. Development of stable Vertebrate Specific Replication Defected ZIKV by selective adaptation3. DNA sequencing of the stably replication-defective in vertebrate cells-ZIKV (VSRD-ZIKV) and analysis ofnew engineered mutations4. Preliminary evaluation of VSRD-ZIKV in both newborn and 3-week-old immunocompromised mice5. Prime-boost VSRD-ZIKV vaccination provides robust protection against lethal ZIKV challenge inimmunocompromised mice6. Vaccination with VSRD-ZIKV is associated with ZIKV-specific humoral immunity and CD8+IFN- + responses7. VSRD-ZIKV provides protection and prevents viral accumulation in the testes of male mice challengedwith lethal ZIKV8. Immunization with VSRD-ZIKV protects against vertical transmission in pregnant mice challenged withlethal ZIKV In addition, we recently published a paper based on this study: Wan S, Cao S, Wang X, Zhou Y, Yan W, Gu X, Wu TC, Pang X. Generation and preliminary characterization of vertebrate-specific replication-defective Zika virus. Virology. 2020 Oct 6;552:73-82. doi: 10.1016/j.virol. 2020.09.001. Online ahead of print. PMID: 33075709 We proposed the I-Corps team included three highly qualified key investigators. Chris D. Ta, MBA. CEO of TenGen Biomedical Co. and he has over seventeen years of experience in industry development; Xiaowu Pang, Ph.D. Principal Investigator of the STTR Phase I project and he has been driving the project; and Xinbin Gu, MD. Ph.D. Co-founder of TenGen Biomedical Co. and Co-Investigator of the STTR Phase I project. Dr. Gu has been leading the visionary on the team. All three members are committed to the time requirements of the program.Project Narrative A I-Corps at NIH Program application from TenGen Biomedical Co. to transfer the Zika vaccine candidate from laboratory to marketplace.