PLoS Pathogens · 2020 · 16 citations · 37 references
Life SciencesInfectious DiseasesMolecular BiologyMolecular VirologyVaccinologyVirologyAntiviral ImmunityRecombinant Protein VaccinesVaccine Antigen DesignViral InfectionsViral TropismViral VaccinesGlycoprotein VaccinesHuman Herpesvirus 6 InfectionMammalian Expression SystemsTransmembrane ProteinsVaccine Candidate AntigensViral Envelope GlycoproteinsViral GlycoproteinsViral Surface Proteins
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.
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IDENTIFICATION OF HUMAN HERPESVIRUS-6 AS A CAUSAL AGENT FOR EXANTHEM SUBITUM
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