Nasal peptide vaccination elicits CD8 responses and reduces viral burden after challenge with virulent murine cytomegalovirus.

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.

Duke Scholars

Author Richard Frothingham Medicine, Infectious Diseases

Author John David Hamilton Medicine, Infectious Diseases

Author Herman Ford Staats Pathology