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