Researchers in the lab of David Knipe have constructed the HSV-1 based vaccine vector HSV-1 d106S. The vector can express viral, bacterial, or cancer gene products and has been used to induce protective immunity in humanized mice against HIV and rhesus macaques against simian immunodeficiency virus (SIV). Further, the vector has a low toxicity profile and avoids concerns with unintended off-target reactions observed with traditional viral vectors as a result of its non-replicating behavior.

Among the vectored antigens developed in the lab is the SARS virus spike protein. This vectored antigen serves as a proof of concept to integrate the SARS-CoV-2 (COVID-19) spike protein antigen into the HSV-1 d106S vector platform, given the striking similarity between SARS and COVID-19.

The team is seeking industrial collaboration with COVID-19 vaccine manufacturers to ensure robust and persistent immune responses.

Developing the HSV-1 d106S vector with the SARS-CoV-2 virus spike protein antigen offers many advantages over existing vaccine vector technologies. First, although HSV-1 is a common infection, pre-existing HSV-1 immunity has little impact on the efficacy of the HSV-1 vaccine vectors in a mouse model. Second, the HSV replication-defective vectors induce a strong Th1 helper T cell response. As such, this vector induces a strong priming immune response. Finally, the d106S virus-based vectors express 10-fold higher levels of transgenes than adenovirus 5-based vectors, thereby enhancing the vaccine efficiency. From a production standpoint, the team has developed a complementing cell line that expresses Cas9 and a CRISPR guide RNA that eliminates parental virus, so recombinant viruses are almost pure in the initial progeny and can be constructed quickly. Collectively, the HSV-1 d106S vaccine vector platform could be used to rapidly make a COVID-19 vaccine to aid in the fight against this global pandemic.