title: Induction of pluripotent protective immunity following immunisation with a chimeric vaccine against human cytomegalovirus.
abstract: Based on the life-time cost to the health care system, the Institute of Medicine has assigned the highest priority for a vaccine to control human cytomegalovirus (HCMV) disease in transplant patients and new born babies. In spite of numerous attempts successful licensure of a HCMV vaccine formulation remains elusive. Here we have developed a novel chimeric vaccine strategy based on a replication-deficient adenovirus which encodes the extracellular domain of gB protein and multiple HLA class I & II-restricted CTL epitopes from HCMV as a contiguous polypeptide. Immunisation with this chimeric vaccine consistently generated strong HCMV-specific CD8(+) and CD4(+) T-cells which co-expressed IFN-gamma and TNF-alpha, while the humoral response induced by this vaccine showed strong virus neutralizing capacity. More importantly, immunization with adenoviral chimeric vaccine also afforded protection against challenge with recombinant vaccinia virus encoding HCMV antigens and this protection was associated with the induction of a pluripotent antigen-specific cellular and antibody response. Furthermore, in vitro stimulation with this adenoviral chimeric vaccine rapidly expanded multiple antigen-specific human CD8(+) and CD4(+) T-cells from healthy virus carriers. These studies demonstrate that the adenovirus chimeric HCMV vaccine provides an excellent platform for reconstituting protective immunity to prevent HCMV diseases in different clinical settings.
authors.affiliation: Australian Centre for Vaccine Development, Tumour Immunology Laboratory, Division of Immunology, Queensland Institute of Medical Research, Brisbane, Australia.
authors.forename: Jie
authors.initials: J
authors.lastname: Zhong
authors.forename: Michael
authors.initials: M
authors.lastname: Rist
authors.forename: Leanne
authors.initials: L
authors.lastname: Cooper
authors.forename: Corey
authors.initials: C
authors.lastname: Smith
authors.forename: Rajiv
authors.initials: R
authors.lastname: Khanna
mesh_terms: D000818:Animals; D000917:Antibody Formation; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D003587:Cytomegalovirus / Q000378:metabolism*; D003586:Cytomegalovirus Infections / Q000517:prevention & control; D022482:Cytomegalovirus Vaccines / Q000627:therapeutic use*; D005805:Genes, MHC Class I; D005802:Genes, MHC Class II; D006801:Humans; D007107:Immune System / Q000821:virology; D051379:Mice; D008822:Mice, Transgenic; D011993:Recombinant Fusion Proteins / Q000737:chemistry; D014612:Vaccines / Q000737:chemistry* / Q000378:metabolism
chemical_list: D022482:Cytomegalovirus Vaccines; D011993:Recombinant Fusion Proteins; D014612:Vaccines