title: Nasal peptide vaccination elicits CD8 responses and reduces viral burden after challenge with virulent murine cytomegalovirus.
abstract: Infection of BALB/c mice with murine cytomegalovirus (MCMV) leads to CD8 cell responses to an immunodominant epitope YPHFMPTNL. We presented this epitope as a nasal peptide vaccine in combination with cholera toxin adjuvant, and evaluated immune responses and protection from MCMV challenge. Vaccination of naive mice generated elevated numbers of peptide-specific interferon-gamma-secreting splenocytes (median 80/million, range 60 to 490), compared to control mice (median 2/million, range -4.5 to 8; P=0.008, Mann-Whitney test). Twelve days after challenge with virulent MCMV, vaccinated mice had a 1.1 log(10) reduction in salivary gland viral titer compared to unvaccinated controls (5.36+/-0.24 vs. 6.42+/-0.12, mean +/-SD log(10) plaque-forming-units; P <0.001, t -test). Mice with chronic MCMV infection had consistent responses to the peptide (183+/-24/million interferon-gamma-secreting splenocytes). Nasal peptide vaccination during chronic infection boosted peptide-specific responses in two of four mice to >900/million interferon-gamma-secreting splenocytes. Nasal peptide vaccination was immunogenic in naïve and MCMV-infected mice, and reduced viral burden in naive mice after virulent MCMV challenge. The nasal route may be useful for peptide presentation by novel human vaccines.
authors.affiliation: Department of Medicine, Duke University Medical Center, Durham, North Carolina 27710, USA.
authors.forename: Indulekha N
authors.initials: IN
authors.lastname: Gopal
authors.forename: Anita
authors.initials: A
authors.lastname: Quinn
authors.forename: Stanley C
authors.initials: SC
authors.lastname: Henry
authors.forename: John D
authors.initials: JD
authors.lastname: Hamilton
authors.forename: Herman F
authors.initials: HF
authors.lastname: Staats
authors.forename: Richard
authors.initials: R
authors.lastname: Frothingham
mesh_terms: D000276:Adjuvants, Immunologic / Q000008:administration & dosage; D000281:Administration, Intranasal; D000818:Animals; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D002772:Cholera Toxin / Q000008:administration & dosage; D006566:Herpesviridae Infections / Q000276:immunology / Q000517:prevention & control* / Q000821:virology; D016056:Immunodominant Epitopes / Q000008:administration & dosage / Q000276:immunology*; D007371:Interferon-gamma / Q000096:biosynthesis; D018655:Lymphocyte Count; D051379:Mice; D008807:Mice, Inbred BALB C; D018146:Muromegalovirus / Q000276:immunology*; D012469:Salivary Glands / Q000821:virology; D013154:Spleen / Q000276:immunology; D014611:Vaccination; D014614:Vaccines, Synthetic / Q000008:administration & dosage / Q000276:immunology; D019562:Viral Load; D014765:Viral Vaccines / Q000008:administration & dosage* / Q000276:immunology*
chemical_list: D000276:Adjuvants, Immunologic; D016056:Immunodominant Epitopes; D014614:Vaccines, Synthetic; D014765:Viral Vaccines; D007371:Interferon-gamma; D002772:Cholera Toxin