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A clinical herpes vaccine is still lacking. In the present study, a novel prime\/pull\/keep vaccine was tested in a human leukocyte antigen transgenic rabbit model of ocular herpes (HLA-A*0201 Tg rabbit). Ten asymptomatic (ASYMP) CD8\n              <jats:sup>+<\/jats:sup>\n              T-cell peptide epitopes and 3 CD4\n              <jats:sup>+<\/jats:sup>\n              T-cell epitopes were selected from the HSV-1 glycoproteins D and B (gD and gB), viral tegument proteins (VP11\/12 and VP13\/14), and the DNA replication-binding helicase (UL9), all preferentially recognized by CD8\n              <jats:sup>+<\/jats:sup>\n              and CD4\n              <jats:sup>+<\/jats:sup>\n              T cells from \u201cnaturally protected\u201d HSV-1-seropositive healthy ASYMP individuals (who never had recurrent corneal herpetic disease). HLA Tg rabbits were ocularly infected with HSV-1, then during latency at day 30 post-infection, the rabbits were ocularly vaccinated with a recombinant neurotropic AAV8 vector (10\n              <jats:sup>7<\/jats:sup>\n              GC\/ eye) encoding for the 10 CD8\n              <jats:sup>+<\/jats:sup>\n              T-cell peptide and 4 CD4\n              <jats:sup>+<\/jats:sup>\n              T-cell peptide (prime), T-cell attracting CXCL-11 (pull), and T-cell keeping IL-2\/IL-15 cytokines (keep). The rabbits were followed up for corneal disease and viral loads in tears for 28 days. The frequency, function, and protective efficacy of HSV-specific CD8\n              <jats:sup>+<\/jats:sup>\n              T cells induced by the prime\/pull\/keep vaccine were assessed in the trigeminal ganglia (TG), cornea, spleen, and peripheral blood. Compared to the mock group (unvaccinated), the peptides\/CXCL11\/IL-2\/IL-15 vaccine generated frequent resident CD8\n              <jats:sup>+<\/jats:sup>\n              T cells that infiltrated the TG. In ocularly HSV-1-infected and prime\/pull\/keep vaccinated rabbits, CD8\n              <jats:sup>+<\/jats:sup>\n              T cell mobilization and retention into TG were associated with a significant reduction in corneal herpes infection and disease. These findings draw attention to the novel prime\/pull\/keep therapeutic vaccine strategy to mobilize and retain antiviral T cells to tissues protecting them against herpetic infection and disease.\n            <\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>IMPORTANCE<\/jats:title>\n            <jats:p>\n              There is an urgent need for a vaccine against widespread human herpes simplex virus infections. The present study demonstrates that immunization of humanized HLA-A*0201 transgenic rabbits with CD8\n              <jats:sup>+<\/jats:sup>\n              and CD4\n              <jats:sup>+<\/jats:sup>\n              T-cell epitope peptides (prime)\/ CXCL11 (pull)\/ IL-2\/IL-15 (keep) AAV8-based vaccine triggered mobilization and retention of HSV-1-specific CD8\n              <jats:sup>+<\/jats:sup>\n              T cells locally in the cornea and TG, the sites of acute and latent herpes infections. Mobilization and retention of antiviral CD8\n              <jats:sup>+<\/jats:sup>\n              T cells into the cornea and TG of HSV-1-infected rabbits that received the prime\/pull\/keep vaccine was associated with protection against ocular herpes infection and disease. These results highlight the importance of the prime\/pull\/keep vaccine strategy to bolster the number and function of protective CD8\n              <jats:sup>+<\/jats:sup>\n              T cells within infected tissues.\n            <\/jats:p>\n          <\/jats:sec>","DOI":"10.1128\/jvi.00135-25","type":"journal-article","created":{"date-parts":[[2025,4,10]],"date-time":"2025-04-10T13:03:12Z","timestamp":1744290192000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":9,"title":["A tissue-targeted prime\/pull\/keep therapeutic herpes simplex virus vaccine protects against recurrent ocular herpes infection and disease in HLA-A*0201 transgenic rabbits"],"prefix":"10.1128","volume":"99","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5410-2593","authenticated-orcid":false,"given":"Aziz A.","family":"Chentoufi","sequence":"first","affiliation":[{"name":"Laboratory of Cellular and Molecular Immunology, Gavin Herbert Eye Institute, University of California Irvine, School of Medicine","place":["Irvine, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3986-890X","authenticated-orcid":false,"given":"Swayam","family":"Prakash","sequence":"additional","affiliation":[{"name":"Laboratory of Cellular and Molecular Immunology, Gavin Herbert Eye Institute, University of California Irvine, School of Medicine","place":["Irvine, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hawa","family":"Vahed","sequence":"additional","affiliation":[{"name":"Laboratory of Cellular and Molecular Immunology, Gavin Herbert Eye Institute, University of California Irvine, School of Medicine","place":["Irvine, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sweta","family":"Karan","sequence":"additional","affiliation":[{"name":"Laboratory of Cellular and Molecular Immunology, Gavin Herbert Eye Institute, University of California Irvine, School of Medicine","place":["Irvine, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Afshana","family":"Quadiri","sequence":"additional","affiliation":[{"name":"Laboratory of Cellular and Molecular Immunology, Gavin Herbert Eye Institute, University of California Irvine, School of Medicine","place":["Irvine, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anthony B.","family":"Nesburn","sequence":"additional","affiliation":[{"name":"Laboratory of Cellular and Molecular Immunology, Gavin Herbert Eye Institute, University of California Irvine, School of Medicine","place":["Irvine, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9468-2521","authenticated-orcid":true,"given":"Lbachir","family":"BenMohamed","sequence":"additional","affiliation":[{"name":"Laboratory of Cellular and Molecular Immunology, Gavin Herbert Eye Institute, University of California Irvine, School of Medicine","place":["Irvine, USA"]},{"name":"Department of Molecular Biology & Biochemistry, University of California Irvine, School of Medicine","place":["Irvine, USA"]},{"name":"Institute for Immunology, University of California Irvine, School of Medicine","place":["Irvine, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_3_2_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.1700145"},{"key":"e_1_3_3_3_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.ppat.1003547"},{"key":"e_1_3_3_4_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.vaccine.2014.10.002"},{"key":"e_1_3_3_5_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.humimm.2014.04.016"},{"key":"e_1_3_3_6_2","doi-asserted-by":"publisher","DOI":"10.1155\/2012\/149135"},{"key":"e_1_3_3_7_2","first-page":"51","article-title":"Current trends in negative immuno-synergy between two sexually transmitted infectious viruses: HIV-1 and HSV-1\/2","volume":"13","author":"Chentoufi AA","year":"2012","unstructured":"Chentoufi AA, Dervillez X, Rubbo P-A, Kuo T, Zhang X, Nagot N, Tuaillon E, Van De Perre P, Nesburn AB, Benmohamed L. 2012. 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