title: Recombinant glycoprotein B vaccine formulation with Toll-like receptor 9 agonist and immune-stimulating complex induces specific immunity against multiple strains of cytomegalovirus.
abstract: Natural human cytomegalovirus (CMV) infection is characterized by a strain-specific neutralizing antibody response. This is particularly relevant in clinical settings such as transplantation and pregnancy where reinfection with heterologous strains occurs and the immune system does not mount an effective response against the infecting strain due to underlying immunosuppression. There is an emerging argument that a CMV vaccine that induces high titres of cross-neutralizing antibodies will be more effective in protecting individuals from infection with antigenically different CMV strains. In addition, induction of cell-mediated immunity offers the additional advantage of targeting virus-infected cells. This study presents a novel formulation of a CMV vaccine that, by combining recombinant soluble gB protein with a Toll-like receptor 9 agonist (CpG ODN1826) and immune-stimulating complexes (AbISCO 100), was able to elicit strong polyfunctional CMV-specific cellular and cross-neutralizing humoral immune responses. These data demonstrated that prime-boost immunization of human leukocyte antigen (HLA)-A2 mice with gB protein in combination with CpG ODN1826 and AbISCO 100 induced long-lasting CMV-specific CD4(+) and CD8(+) T-cell and humoral responses. Furthermore, these responses neutralized infection with multiple strains of CMV expressing different gB genotypes and afforded protection against challenge with recombinant vaccinia virus encoding the gB protein. These observations argue that this novel vaccine strategy, if applied to humans, should facilitate the generation of a robust, pluripotent immune response, which may be more effective in preventing infection with multiple strains of CMV.
authors.affiliation: Griffith Medical Research College, Griffith University, Brisbane, QLD, Australia.|Australian Centre for Vaccine Development, Queensland Institute of Medical Research, Division of Immunology, Herston, QLD, Australia.
authors.forename: Vijayendra
authors.initials: V
authors.lastname: Dasari
authors.affiliation: Australian Centre for Vaccine Development, Queensland Institute of Medical Research, Division of Immunology, Herston, QLD, Australia.
authors.forename: Corey
authors.initials: C
authors.lastname: Smith
authors.affiliation: Australian Centre for Vaccine Development, Queensland Institute of Medical Research, Division of Immunology, Herston, QLD, Australia.
authors.forename: Jie
authors.initials: J
authors.lastname: Zhong
authors.affiliation: Virology Division, Department of Microbiology, SEALS, Prince of Wales Hospital, Randwick, NSW, Australia.|School of Biotechnology and Bimolecular Sciences, University of New South Wales, Sydney, NSW, Australia.
authors.forename: Gillian
authors.initials: G
authors.lastname: Scott
authors.affiliation: Virology Division, Department of Microbiology, SEALS, Prince of Wales Hospital, Randwick, NSW, Australia.|School of Biotechnology and Bimolecular Sciences, University of New South Wales, Sydney, NSW, Australia.
authors.forename: William
authors.initials: W
authors.lastname: Rawlinson
authors.affiliation: Australian Centre for Vaccine Development, Queensland Institute of Medical Research, Division of Immunology, Herston, QLD, Australia.
authors.forename: Rajiv
authors.initials: R
authors.lastname: Khanna
mesh_terms: D000276:Adjuvants, Immunologic / Q000008:administration & dosage*; D000818:Animals; D057134:Antibodies, Neutralizing / Q000097:blood; D000914:Antibodies, Viral / Q000097:blood; D000936:Antigen-Antibody Complex / Q000008:administration & dosage; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D022482:Cytomegalovirus Vaccines / Q000008:administration & dosage / Q000276:immunology*; D005260:Female; D006801:Humans; D007117:Immunization, Secondary / Q000379:methods; D051379:Mice; D008822:Mice, Transgenic; D009838:Oligodeoxyribonucleotides / Q000008:administration & dosage*; D051217:Toll-Like Receptor 9 / Q000819:agonists; D014611:Vaccination / Q000379:methods; D014614:Vaccines, Synthetic / Q000008:administration & dosage / Q000276:immunology; D014759:Viral Envelope Proteins / Q000008:administration & dosage / Q000276:immunology*
chemical_list: D000276:Adjuvants, Immunologic; D057134:Antibodies, Neutralizing; D000914:Antibodies, Viral; D000936:Antigen-Antibody Complex; C408982:CPG-oligonucleotide; D022482:Cytomegalovirus Vaccines; D009838:Oligodeoxyribonucleotides; D051217:Toll-Like Receptor 9; D014614:Vaccines, Synthetic; D014759:Viral Envelope Proteins; C040495:glycoprotein B, Simplexvirus