Journal
VIRUSES-BASEL
Volume 14, Issue 11, Pages -Publisher
MDPI
DOI: 10.3390/v14112474
Keywords
respiratory syncytial virus; RSV; vaccine; attachment protein; G protein; prefusion F
Categories
Funding
- National Institutes of Health [R21AI128520]
- National Institute of General Medical Sciences [P20GM103648]
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The study utilized a novel vaccine to enhance the induction of anti-G antibodies against RSV, resulting in improved protection in mice experiments.
The human respiratory syncytial virus (RSV) is a major cause of severe respiratory tract disease, and a vaccine is not available. We previously reported a novel live vaccine expressing prefusion-stabilized fusion protein (preF) in place of the native F protein (RSV-preF(Delta CT)). As preF is non-functional, RSV-preF(Delta CT) was amplified in a production line expressing a functional substitute, and exhibited a single-cycle replication phenotype, which holds several unique potential advantages. RSV-preF(Delta CT) prevented shedding and lung pathology after viral challenge in mice, but induced low levels of anti-attachment protein (G) antibodies (Abs). Given the significant contributions of anti-G Abs toward disease prevention, we generated modifications to RSV-preF(Delta CT) in an effort to induce higher anti-G Ab levels. The Ab levels were monitored after the prime-boost vaccination of mice with modified vaccines. The most successful modification for enhancing induced anti-G Abs was seen with the placement of G in the first genome position. This vaccine also reduced the pathology after challenge with a high dose of wt RSV, and outperformed the sera from wt RSV-vaccinated mice in in vitro neutralization. Thus, raising the anti-G Ab levels induced by RSV-preF(Delta CT) enhanced efficacy in vitro and in vivo, and constitutes an important next step in developing a live, single-cycle, efficacious vaccine for the human population.
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