Generation Of A Live Attenuated Influenza Vaccine That Elicits Broad Protection
SUMMARY
UCLA researchers in the Department of Microbiology, Immunology & Molecular Genetic and the Molecular Biology Institute have developed a novel method of generating highly efficacious and live attenuated influenza vaccines.
BACKGROUND
The market for human influenza vaccines is expected to reach $4.4 billion by 2021. The majority of these vaccines focus on inactivated or killed viruses, but attenuated vaccines are beneficial in that they stimulate a broader immune response, do not require booster shots, and often require less antigen. However, recent formulations of live attenuated influenza vaccines (LAIVs) have not been efficacious. Therefore, there is significant need for novel strategies for generating effective and broadly protective LAIVs.
INNOVATION
Professor Cheng and coworkers have developed a novel method of generating LAIVs with high efficacy and attenuation. A library of LAIV candidates was generated through transposon mutagenesis of an H1 influenza strain and screened forin vivogrowth profiles in mice. Hits generated from this approach yielded a LAIV that was 100-fold attenuated compared to wild type and was even tolerated in neonatal mice. The identified mutation could be inserted into a different influenza strain to generate similar attenuation. The mutant H1 strain successfully protected mice and ferrets from lethal challenges with heterologous strains (H3 and H5) and was more efficacious than the FDA-approved FluMist.
APPLICATIONS
- Influenza vaccine
- Herpesvirus vaccine
- Zika virus vaccine
- Chikungunya vaccine
- Other live attenuated vaccines
ADVANTAGES
- No comprehensive understanding of gene function required
- Enables profiling of entire genome
- LAIV strains up to 100x attenuated compared to wild type
- Tolerated in neonatal mice
- Greater protection than FDA-approved FluMist
STATE OF DEVELOPMENT
A library of LAIV candidates has been developed and RNA was characterized. Growth of the viruses was carried out in mice and leading candidates were used for vaccination.
RELATED MATERIALS
Wang L, Liu SY, Chen HW, Xu J, Chapon M, Zhang T, Zhou F, Wang YE, Quanquin N, Wang G, Tian X, He Z, Liu L, Yu W, Sanchez DJ, Liang Y, Jiang T, Modlin R, Bloom BR, Li Q, Deng JC, Zhou P, Qin FX, Cheng G, Generation of a Live Attenuated Influenza Vaccine that Elicits Broad Protection in Mice and Ferrets, Cell Host & Microbe., 2017.