Tetrameric glycoprotein complex gH/gL/gQ1/gQ2 is a promising vaccine candidate for human herpesvirus 6B

Primary infection of human herpesvirus 6B (HHV-6B) occurs in infants after the decline of maternal immunity and causes exanthema subitum accompanied by a high fever, and it occasionally develops into encephalitis resulting in neurological sequelae. There is no effective prophylaxis for HHV-6B, and its development is urgently needed. The glycoprotein complex gH/gL/gQ1/gQ2 (called 'tetramer of HHV-6B') on the virion surface is a viral ligand for its cellular receptor human CD134, and their interaction is thus essential for virus entry into the cells. Herein we examined the potency of the tetramer as a vaccine candidate against HHV-6B. We designed a soluble form of the tetramer by replacing the transmembrane domain of gH with a cleavable tag, and the tetramer was expressed by a mammalian cell expression system. The expressed recombinant tetramer is capable of binding to hCD134. The tetramer was purified to homogeneity and then administered to mice with aluminum hydrogel adjuvant and/or CpG oligodeoxynucleotide adjuvant. After several immunizations, humoral and cellular immunity for HHV-6B was induced in the mice. These results suggest that the tetramer together with an adjuvant could be a promising candidate HHV-6B vaccine. Author summary Human herpesvirus 6B (HHV-6B) is known as the cause of the common childhood febrile illness exanthem subitum in its primary infection, and it develops into a lifelong latent infection in almost all individuals. Severe complications such as meningitis and encephalitis can occur in both the primary infection and reactivation. There is no established treatment or vaccine. The tetrameric glycoprotein complex gH/gL/gQ1/gQ2 (tetramer) on the viral envelope is the ligand for the entry of HHV-6B, which is the critical part for its infection. Here, we established a soluble form of the tetramer and purified it to homogeneity. After several immunizations of tetramer along with different combinations of adjuvants in mice, we observed that it greatly induced defensive immunity against HHV-6B, indicating that the tetramer has the potential to become a vaccine candidate. Moreover, our results also revealed that combinations of distinct adjuvants with the tetramer would be useful as an HHV-6B vaccine strategy for different purposes.