title: Protective MCMV immunity by vaccination of the salivary gland via Wharton's duct: replication-deficient recombinant adenovirus expressing individual MCMV genes elicits protection similar to that of MCMV.
abstract: Salivary glands, a major component of the mucosal immune system, confer antigen-specific immunity to mucosally acquired pathogens. We investigated whether a physiological route of inoculation and a subunit vaccine approach elicited MCMV-specific and protective immunity. Mice were inoculated by retrograde perfusion of the submandibular salivary glands via Wharton's duct with tcMCMV or MCMV proteins focused to the salivary gland via replication-deficient adenovirus expressing individual MCMV genes (gB, gH, IE1; controls: saline and replication deficient adenovirus without MCMV inserts). Mice were evaluated for MCMV-specific antibodies, T-cell responses, germinal center formation, and protection against a lethal MCMV challenge. Retrograde perfusion with tcMCMV or adenovirus expressed MCMV proteins induced a 2- to 6-fold increase in systemic and mucosal MCMV-specific antibodies, a 3- to 6-fold increase in GC marker expression, and protection against a lethal systemic challenge, as evidenced by up to 80% increased survival, decreased splenic pathology, and decreased viral titers from 10(6) pfu to undetectable levels. Thus, a focused salivary gland immunization via a physiological route with a protein antigen induced systemic and mucosal protective immune responses. Therefore, salivary gland immunization can serve as an alternative mucosal route for administering vaccines, which is directly applicable for use in humans.
authors.affiliation: 1Stony Brook University, School of Dental Medicine, Department of Oral Biology and Pathology, Stony Brook, NY 11794, USA. steven.london@stonybrook.edu.
authors.forename: Guangliang
authors.initials: G
authors.lastname: Liu
authors.forename: Fangfang
authors.initials: F
authors.lastname: Zhang
authors.forename: Ruixue
authors.initials: R
authors.lastname: Wang
authors.forename: Lucille
authors.initials: L
authors.lastname: London
authors.forename: Steven D
authors.initials: SD
authors.lastname: London
mesh_terms: D000256:Adenoviridae / Q000235:genetics; D000818:Animals; D000914:Antibodies, Viral / Q000097:blood / Q000276:immunology; D004274:DNA, Recombinant; D005260:Female; D005455:Fluorescent Antibody Technique; D015870:Gene Expression / Q000276:immunology; D018858:Germinal Center / Q000276:immunology / Q000378:metabolism; D006566:Herpesviridae Infections / Q000276:immunology / Q000517:prevention & control / Q000821:virology; D006801:Humans; D017874:Immediate-Early Proteins / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D007109:Immunity / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D018146:Muromegalovirus / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D051757:PAX5 Transcription Factor / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D018987:Salivary Ducts / Q000276:immunology* / Q000378:metabolism; D012469:Salivary Glands / Q000276:immunology* / Q000378:metabolism; D013601:T-Lymphocytes / Q000276:immunology / Q000378:metabolism; D014611:Vaccination / Q000379:methods; D014764:Viral Proteins / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D014765:Viral Vaccines / Q000008:administration & dosage / Q000276:immunology; D014779:Virus Replication / Q000235:genetics
chemical_list: D000914:Antibodies, Viral; D004274:DNA, Recombinant; C088645:IE1 protein, cytomegalovirus; D017874:Immediate-Early Proteins; D051757:PAX5 Transcription Factor; C497282:Pax5 protein, mouse; D014764:Viral Proteins; D014765:Viral Vaccines
keywords: inflammation; mucosal immunity; vaccine development