title: Recombinant herpesvirus glycoprotein G improves the protective immune response to Helicobacter pylori vaccination in a mouse model of disease.
abstract: Alphaherpesviruses, which have co-evolved with their hosts for more than 200 million years, evade and subvert host immune responses, in part, by expression of immuno-modulatory molecules. Alphaherpesviruses express a single, broadly conserved chemokine decoy receptor, glycoprotein G (gG), which can bind multiple chemokine classes from multiple species, including human and mouse. Previously, we demonstrated that infection of chickens with an infectious laryngotracheitis virus (ILTV) mutant deficient in gG resulted in altered host immune responses compared to infection with wild-type virus. The ability of gG to disrupt the chemokine network has the potential to be used therapeutically. Here we investigated whether gG from ILTV or equine herpesvirus 1 (EHV-1) could modulate the protective immune response induced by the Helicobacter pylori vaccine antigen, catalase (KatA). Subcutaneous immunisation of mice with KatA together with EHV-1 gG, but not ILTV gG, induced significantly higher anti-KatA IgG than KatA alone. Importantly, subcutaneous or intranasal immunisation with KatA and EHV-1 gG both resulted in significantly lower colonization levels of H. pylori colonization following challenge, compared to mice vaccinated with KatA alone. Indeed, the lowest colonization levels were observed in mice vaccinated with KatA and EHV-1 gG, subcutaneously. In contrast, formulations containing ILTV gG did not affect H. pylori colonisation levels. The difference in efficacy between EHV-1 gG and ILTV gG may reflect the different spectrum of chemokines bound by the two proteins. Together, these data indicate that the immuno-modulatory properties of viral gGs could be harnessed for improving immune responses to vaccine antigens. Future studies should focus on the mechanism of action and whether gG may have other therapeutic applications.
authors.affiliation: Centre for Animal Biotechnology, Faculty of Veterinary Science, The University of Melbourne, Parkville, VIC, Australia.
authors.forename: Louise
authors.initials: L
authors.lastname: Baker
authors.affiliation: Asia-Pacific Centre for Animal Health, Faculty of Veterinary Science, The University of Melbourne, Parkville, VIC, Australia.
authors.forename: Andre M L
authors.initials: AM
authors.lastname: Chitas
authors.affiliation: Centre for Equine Infectious Disease, Faculty of Veterinary Science, The University of Melbourne, Parkville, VIC, Australia.
authors.forename: Carol A
authors.initials: CA
authors.lastname: Hartley
authors.affiliation: Asia-Pacific Centre for Animal Health, Faculty of Veterinary Science, The University of Melbourne, Parkville, VIC, Australia.
authors.forename: Mauricio J C
authors.initials: MJ
authors.lastname: Coppo
authors.affiliation: Asia-Pacific Centre for Animal Health, Faculty of Veterinary Science, The University of Melbourne, Parkville, VIC, Australia.
authors.forename: Paola K
authors.initials: PK
authors.lastname: Vaz
authors.affiliation: Centre for Animal Biotechnology, Faculty of Veterinary Science, The University of Melbourne, Parkville, VIC, Australia.
authors.forename: Andrew
authors.initials: A
authors.lastname: Stent
authors.affiliation: Centre for Equine Infectious Disease, Faculty of Veterinary Science, The University of Melbourne, Parkville, VIC, Australia.
authors.forename: James R
authors.initials: JR
authors.lastname: Gilkerson
authors.affiliation: Asia-Pacific Centre for Animal Health, Faculty of Veterinary Science, The University of Melbourne, Parkville, VIC, Australia.
authors.forename: Joanne M
authors.initials: JM
authors.lastname: Devlin
authors.affiliation: Centre for Animal Biotechnology, Faculty of Veterinary Science, The University of Melbourne, Parkville, VIC, Australia.
authors.forename: Alison L
authors.initials: AL
authors.lastname: Every
mesh_terms: D000818:Animals; D001428:Bacterial Vaccines / Q000008:administration & dosage / Q000276:immunology*; D002374:Catalase / Q000008:administration & dosage / Q000276:immunology; D016207:Cytokines / Q000276:immunology; D004195:Disease Models, Animal; D005260:Female; D006023:Glycoproteins / Q000008:administration & dosage / Q000276:immunology*; D016481:Helicobacter Infections / Q000276:immunology / Q000517:prevention & control*; D016480:Helicobacter pylori / Q000201:enzymology / Q000276:immunology*; D004861:Herpesvirus 1, Equid / Q000276:immunology*; D001352:Herpesvirus 1, Gallid / Q000276:immunology*; D006801:Humans; D007109:Immunity; D007114:Immunization; D051379:Mice; D008807:Mice, Inbred BALB C; D014759:Viral Envelope Proteins / Q000008:administration & dosage / Q000276:immunology*
chemical_list: D001428:Bacterial Vaccines; D016207:Cytokines; D006023:Glycoproteins; D014759:Viral Envelope Proteins; C083103:glycoprotein G, Equid herpesvirus 1; D002374:Catalase