- Lectures
- Institute of Biomedical Sciences
- Location
B1B Lecture Room, IBMS
- Speaker Name
Dr. Yi-Ling Lin (Distinguished Research Fellow)
- State
Definitive
- Url
Dengue fever, caused by four closely related but antigenically distinct serotypes (DENV-1 to DENV-4), has long challenged vaccine developers. Infection with one serotype provides life-long immunity against that serotype, but only short-term cross-protection against the others. Subsequent infection with a different serotype increases the risk of severe disease due to antibody-dependent enhancement (ADE) — a unique immunopathologic phenomenon where non-neutralizing antibodies worsen viral replication and inflammation. Thus, the development of dengue vaccines has been both scientifically complex and clinically challenging, due to the co-circulation of four dengue serotypes and the risk of ADE. To overcome this challenge, we explore vectored immunoprophylaxis (VIP), which involves the passive transfer of protective antibody genes via viral vectors for in vivo expression. We utilized a recombinant adeno-associated virus (rAAV) to express a broad anti-flavivirus neutralizing human monoclonal antibody, bnAb 752-2C8, and tested its protection against four serotypes of DENV and Zika virus (ZIKV). The bnAb 752-2C8 antibody gene was cloned into an AAV plasmid and the rAAV was successfully generated to express bnAb 752-2C8. After a single dose of rAAV administration into AGB6 mice, the human antibody concentrations increased and remained elevated for at least 48 weeks. VIP-treated mice were completely protected from a lethal challenge of DENVs and ZIKV, while control mice without bnAb 752-2C8 succumbed to infection. Our results demonstrate the effectiveness of rAAV in delivering bnAb 752-2C8 for long-term protection against multiple flaviviruses, providing a potential strategy to control flavivirus infections and possibly other viral diseases.
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