CpG dinucleotide enrichment in the influenza A virus genome as a live attenuated vaccine development strategy

• DOI: 10.1371/journal.ppat.1011357
• Publication Date: 2023-05-05T17:39:40Z
• Authors: Colin P. Sharp; Beth H. Thompson; Tessa J. Nash; Ola Diebold; Rute M. Pinto; Luke Thorley; Yao-Tang Lin; Samantha Sives; Helen Wise; Sara Clohisey Hendry; Finn Grey; Lonneke Vervelde; Peter Simmonds; Paul Digard; Eleanor R. Gaunt
• Keywords: CpG site; Attenuated vaccine

Synonymous recoding of RNA virus genomes is a promising approach for generating attenuated viruses to use as vaccines. Problematically, typically hinders growth, but this may be rectified using CpG dinucleotide enrichment. CpGs are recognised by cellular zinc-finger antiviral protein (ZAP), and so in principle, removing ZAP sensing from propagation system will reverse attenuation CpG-enriched virus, enabling high titre yield vaccine virus. We tested strain influenza A (IAV) engineered increased content genome segment 1. Virus was mediated the short isoform ZAP, correlated with number added, enacted via turnover viral transcripts. The strongly mice, yet conveyed protection potentially lethal challenge dose wildtype Importantly development, were genetically stable during serial passage. Unexpectedly, both MDCK cells embryonated hens' eggs that used propagate live vaccines, ZAP-sensitive fully replication competent. Thus, enriched defective human systems can systems, providing realistic, economically viable platform augment existing