Ren Sun Group

VACCINE DEVELOPMENT

Enable precision engineering of broad-spectrum influenza virus vaccine

1.  Define the function of viral genomes at single nucleotide resolution

2. Systematic identification of IFN-sensitive mutations

IFN response provides the first line of defense against viral infections; and it is also critical for maturation of dendritic cells and macrophages, development of B and T cells, and memory formation, bridging innate and adaptive immunity.

Most viruses have evolved to efficiently suppress the production and function of IFN to allow replication in vivo.

3. Systematic elimination of IFN-modulating functions from the virus

By incorporating eight IFN-sensitive mutations (indicated by red dots), we generated a hyper–interferon-sensitive (HIS) virus as a vaccine candidate. HIS virus is highly attenuated in IFN-competent hosts but able to induce high transient local IFN responses, elicits robust humoral and cellular immune responses, and provides protection against homologous and heterologous viral challenges in animal model.

This method is broadly applicable to vaccine development against other pathogens or cancers.

Du et al, Science 2018