Cross-sectional analysis of CD8 T cell immunity to HHV-6B identifies new targets for adoptive T cell therapy

Until recently, the HHV-6 CD8 T cell repertoires has been largely uncharacterized, in contrast to EBV and CMV. Previously, only five of the 98 unique HHV-6B proteins were examined, all chosen due to their homology to CMV. A group from the German Center for Infection Research led by Andreas Moosmann, PhD, targeted all HHV-6B proteins but focused on only one HLA class I allotype.  The group found U86-specific T cells readily in most donors and patients and concluded that U86 is a strong candidate for an immunodominant CD8 T cell antigen of HHV-6.

Andreas Moosmann, PhD, Group Leader DZIF Research Group, Host Control of Viral Latency and Reactivation

The group also concluded that, contrary to expectations, immunity to CMV has limited ability to predict the specificity of CD8 T cell responses to HHV-6.  In addition, they found that the diversity of epitopes and antigens available for presentation by infected cells is distinctly larger in HHV-6 than for EBV and CMV.

A commercial firm, Viracyte, is developing “off the shelf” cytotoxic CD8 T cell immunotherapy for HHV-6 as well as for EBV, adenovirus, BK virus and CMV.  The work is based on studies done by Baylor, in which HHV-6 U11, U14 and U90 were defined as targets, based on CMV homologs. The group reported excellent results in a small phase II clinical trial of multi-virus specific T cells administered to 38 patients with 45 infections (Tzannou 2017).

Cell Medica and Atara Biotherapeutics are also working on cytotoxic T cell therapies for EBV associated malignancies as well as CMV disease.

The German group’s findings will be helpful to groups searching for effective immune and vaccine therapies. Read the full paper: Martin 2018.