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.