Intranasal immunization with a replication-deficient adenovirus vector expressing glycoprotein H of murine cytomegalovirus induces mucosal and systemic immunity.
A vaccine vector, designated AdV-gH, was constructed by inserting the complete open reading frame of MCMV gH under control of the human CMV IE-1 promoter into the E-1 region of a replication-deficient adenovirus 5. In vitro infection of QB1-293 cells and mouse embryo cells with AdV-gH resulted in expression of MCMV gH detected by IFA. Immunization of BALB/c mice with AdV-gH (1 x 10(7) PFU) given by the intranasal route induced a humoral response with antibody detected in serum of 100% of vaccines. Antibody to MCMV gH was also detected in the bronchoalveolar lavage, fecal suspensions and vaginal washings. The viral titer of lung and salivary gland of immunized mice 10 days after intranasal challenge with MCMV (1 x 10(5) PFU) were significantly reduced compared to controls, but virus infection was not prevented. Re-exposure of mice to AdV-gH 30 days after primary immunization induced a significant boost of serum antibody response. When rechallenged with MCMV intranasally, these mice had further reduction of MCMV titers in the lung and salivary glands. Such a strategy may be important in reducing horizontal transmission of CMV infections across mucosal surfaces and in altering host immunity to CMV.
Shanley
John D
JD
Department of Medicine, University of Connecticut Health Center, 263 Farmington Avenue, CT 06030, USA. jshanley@nso1.uchc.edu
Wu
Carol A
CA
D000256:Adenoviridae / Q000276:immunology; D000281:Administration, Intranasal; D000818:Animals; D045744:Cell Line, Tumor; D002478:Cells, Cultured; D003587:Cytomegalovirus / Q000276:immunology; D022482:Cytomegalovirus Vaccines / Q000008:administration & dosage* / Q000276:immunology*; D003673:Defective Viruses / Q000235:genetics* / Q000276:immunology; D005260:Female; D005822:Genetic Vectors; D006801:Humans; D051379:Mice; D008807:Mice, Inbred BALB C; D009297:Nasal Mucosa / Q000276:immunology* / Q000821:virology; D011247:Pregnancy; D014759:Viral Envelope Proteins / Q000008:administration & dosage* / Q000096:biosynthesis / Q000235:genetics / Q000276:immunology*
D022482:Cytomegalovirus Vaccines; D014759:Viral Envelope Proteins; C071440:glycoprotein H, Cytomegalovirus; C499358:glycoprotein H, Human cytomegalovirus