Topical Ocular Mucosal Immunization with Herpes Simplex Virus Type 1 Epitope Peptide Epitopes: The Role of the Nasal Immune System Ayesha Akhtarmalik Mentor: Lbachir BenMohamed We recently reported that topical ocular delivery of herpes simplex virus type 1 glycoprotein D (HSV-1 gD) peptide epitopes plus CpG2007 adjuvant efficiently induces both ocular mucosal and systemic immune responses. We now demonstrate that topical ocular delivery of HSV-gD peptide epitopes plus CpG2007 adjuvant induced both systemic and ocular mucosal immune responses at the same levels as intranasal immunizations. The immune responses elicited after topical ocular versus intranasal delivery of HSV-gD peptide epitopes plus CpG2007 adjuvant were measured by observing specific T cell responses in both the spleen and conjunctiva using CFSE assays, and by the detection of the levels of serum and tear antibodies using ELISA assays. In addition, the effect of nasolacrimal ducts blockade on the ocular immunogenicty was investigated. Following a surgical nasolacrimal ducts blockade, the ocular delivery, but not intranasal delivery of HSV peptides plus CpG2007 further enhanced systemic T cell response, but had no effect on the ocular mucosal T cell responses. Although the intranasal route resulted in both systemic and mucosal immune responses, it failed to protect against ocular herpes infection as compared to topical ocular route. Topical ocular administration of HSV-1 gD peptide epitopes plus CpG2007 adjuvant appears as a noninvasive vaccination method. The nasal lymphoid system appears to influence the ocular immunity induced following topical ocular immunization with HSV-1 gD peptides.