Enhancing Anti-G Antibody Induction by a Live Single-Cycle Prefusion F-Expressing RSV Vaccine Improves In Vitro and In Vivo Efficacy

• Published in: Viruses 2022-11, Vol.14 (11), p.2474
• Main Authors: Lamichhane, Pramila, Terhüja, Megolhubino, Snider, Timothy A, Oomens, Antonius G P
• Format: Article
• Language: English
• Subjects: Animals; Antibodies; Antibodies, Neutralizing; Antibodies, Viral; Antigens; attachment protein; Cloning; F protein; Fusion protein; G protein; Genomes; Health aspects; Humans; Immunization; Infections; Mice; Mutagenesis; Mutation; Pathology; Phenotypes; Plasmids; prefusion F; Product development; Proteins; Respiratory syncytial virus; Respiratory Syncytial Virus Infections; Respiratory Syncytial Virus Vaccines; Respiratory Syncytial Virus, Human - genetics; Respiratory tract diseases; RSV; vaccine; Vaccines; Viral antibodies; Viral Fusion Proteins - genetics; Viral vaccines; Virulence; Viruses
• ISSN: 1999-4915; 1999-4915
• DOI: 10.3390/v14112474

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 ). As preF is non-functional, RSV-preF 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 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 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 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.