Abstract
Human herpesvirus 6 (HHV-6) infects over 90% of people. The HHV-6 subtype, HHV-6B in particular, is often associated with exanthem subitum in early childhood. Exanthem subitum is usually self-limiting and good prognosis disease; however, some infants primarily infected with HHV-6B develop encephalitis/encephalopathy, and half of the patients developed encephalopathy reported to have neurological sequelae. Furthermore, after primary infection, HHV-6B remains in a latent state and sometimes reactivated in immunosuppressed patients, causing life-threatening severe encephalopathy. However, effective immunotherapies or vaccines for controlling HHV-6B infection and reactivation have not yet been established. Recently, we have found that the HHV-6B tetrameric glycoprotein (g) complex, gH/gL/gQ1/gQ2 is a promising vaccine candidate, and currently under preclinical development. To confirm our vaccine candidate protein complex induce detectable T-cell responses, in this study, we comprehensively screened CD4+ and CD8+ T-cell epitopes in the gH/gL/gQ1/gQ2 tetrameric complex protein in mice immunisation model. Both BALB/c and C57BL/6 mice were immunised with the tetrameric complex protein or plasmid DNA encoding gH, gL, gQ1, and gQ2, and then restimulated with 162 20-mer peptides covering the whole gH/gL/gQ1/gQ2 sequences; multiple CD4+ and CD8+ T-cell-stimulating peptides were identified in both BALB/c and C57BL/6 mice. Our study demonstrates that gH/gL/gQ1/gQ2 tetramer-targeted vaccination has potential to induce T-cell responses in two different strains of mice and supports the future development and application of T-cell-inducing vaccine and immunotherapies against HHV-6B.
Highlights
Both HHV-6A and HHV-6B have been shown to be involved in human diseases [4, 5], HHV-6B infection is clearly associated with exanthem subitum in early childhood [1, 6]
We identified that HHV-6B gQ1 protein-induced CD4+ and CD8+ T-cell responses by immunising BALB/c mice using DNA vaccination [21]
In our previous study, gQ1-expressing plasmid vaccination induced at least one CD4+ T-cell response and one CD8+ T-cell response in gQ1 protein in BALB/c mice [21], so we expected that immunisation with gH/gL/gQ1/gQ2 tetrameric protein complex with CpG adjuvant would induce at least one CD4+ T-cell response and one CD8+ T-cell response
Summary
Human herpesvirus 6 (HHV-6) belongs to the β-herpesvirus subfamily and infects over 90% of people globally [1]. HHV6 can be classified into two groups, variant A (HHV-6A) and variant B (HHV-6B), by their epidemiology and pathology [2, 3]. Both HHV-6A and HHV-6B have been shown to be involved in human diseases [4, 5], HHV-6B infection is clearly associated with exanthem subitum in early childhood [1, 6]. Journal of Immunology Research with a good prognosis; it is relatively highly associated with febrile seizure. It is rare, some infants develop encephalitis/encephalopathy associated with HHV-6B infection. There is no specific drug, no vaccines, and no cellular immunotherapy for controlling HHV-6B infection and reactivation has been established
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