The development of Chinese specific human cytomegalovirus polyepitope recombinant vaccine

Abstract

Human cytomegalovirus (HCMV) infection is a major cause of morbidity in the recipients of organ transplants and in the congenitally infected infants. HCMV vaccine has emerged as an effective approach to prevent HCMV infection particularly for the development of multiple viral antigens vaccination and human leukocyte antigen (HLA)-restricted polyepitope technology. As the Chinese population makes up more than one fifth of the population worldwide, it is important to develop HCMV vaccines more specific for the Chinese population by targeting Chinese-restricted HLA alleles and antigens. In the present study, we designed a novel chimeric polyepitope vaccine based on the replication-deficient adenovirus Ad5F35, which encodes 83 HCMV T cell epitopes from 15 different HCMV antigens, restricted to 14 HLA I and 7 HLA II alleles that cover 92% of the Chinese population. Our results show that the recombinant adenovirus vaccine Ad5F35-CTL·Th can be efficiently transfected and expressed in peripheral blood mononuclear cells (PBMCs) with little cytopathic activity. Ad5F35-CTL·Th can also be endogenously processed and presented by PBMCs. Ad5F35-CTL·Th-stimulated HCMV-specific cytotoxic T lymphocytes (CTLs) showed strong cytolytic activity against HCMV polyepitope-sensitized target cells. The CTL activity was accompanied by high levels of IFN-γ production after Ad5F35-CTL·Th stimulation. The specificity and vigorous response to the recombinant adenovirus vaccine in vitro makes it a potential candidate to be used for transplantation recipients or congenitally infected infants.