{
  "abstract": "Background: Recurrent ocular herpetic disease is a leading infectious cause of corneal blindness and is associated with psychological distress, anxiety, and social withdrawal. No ocular herpes vaccine or immunotherapy currently exists. Hypothesis: A prime/pull/keep (PPK) T-cell immunotherapy, built on HSV-1 epitopes preferentially recognized by CD8+/CD4+ T cells from naturally protected asymptomatic (ASYMP) individuals, would reduce viral reactivation, shedding, recurrent corneal disease, and associated neurobehavioral deficits. Methods: Immunodominant HLA-restricted CD8+/CD4+ epitopes from HSV-1 gD/gB, tegument proteins VP11/12/VP13/14, and helicase UL9 were delivered via topical ocular AAV8 vector (prime) to latently infected HLA-A*0201/DRB1 mice, combined with chemokine CXCL11 (pull) and IL-2/IL-15 cytokines to sustain TRM cells (keep), then UVB-exposed to trigger reactivation and recurrent corneal disease. Results: PPK immunotherapy conferred robust, near-complete protection against recurrent HSV-1 disease and improved survival after UVB-induced reactivation, unlike its individual components. This protection was associated with site-specific accumulation of HSV-1-specific CD8+/CD4+ TRM cells in the cornea and trigeminal ganglia (TG), but not in the spleen, with peak retention from combined IL-2/IL-15, alongside durable central/effector memory populations. PPK-induced T cells showed enhanced polyfunctionality (cytokine production, cytotoxicity, proliferation), reduced exhaustion markers, and a TCF-1+ self-renewing phenotype. PPK also elicited robust, Th1-biased HSV-1-specific IgG responses complementing mucosal immunity, and restored spatial memory, reduced depression-like behavior, and reversed social withdrawal in mice with recurrent ocular herpes. Conclusion: PPK immunotherapy induces potent, durable antiviral TRM cells at primary sites of HSV-1 latency and reactivation, protecting against recurrent ocular herpetic disease and alleviating associated neurobehavioral deficits, supporting its translational potential in humans.",
  "abstract_shown": true,
  "affiliations": [
    "UC Irvine, School of Medicine"
  ],
  "article_type": "New results",
  "arxiv": null,
  "author_total": 8,
  "authors": [
    {
      "name": "S. Karan"
    },
    {
      "name": "S. Prakash"
    },
    {
      "name": "A. A. Chentoufi"
    },
    {
      "name": "K. Intharachalit"
    },
    {
      "name": "S. X. L. Ng"
    },
    {
      "name": "J. Hwang"
    },
    {
      "name": "C. Maurya"
    },
    {
      "affs": [
        0
      ],
      "name": "L. BENMOHAMED"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/5ke7490e9z7jy.bib",
  "cited_by": 0,
  "doi": "10.64898/2026.09.27.754856",
  "fulltext_url": "https://www.biorxiv.org/content/10.64898/2026.09.27.754856v1.full",
  "id": "5ke7490e9z7jy",
  "issns": [],
  "landing_url": "https://www.biorxiv.org/content/10.64898/2026.09.27.754856v1",
  "language": null,
  "licence": "CC-BY-NC-ND",
  "licence_label": "CC BY-NC-ND",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by-nc-nd/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "biorxiv",
      "immunology"
    ],
    [
      "openalex",
      "2713|Herpesvirus Infections and Treatments"
    ]
  ],
  "openalex": "W7216101780",
  "pdf_url": "https://www.biorxiv.org/content/10.64898/2026.09.27.754856v1.full.pdf",
  "pmcid": null,
  "pmid": null,
  "published": "2026-09-27",
  "publisher": null,
  "ris": "https://research.draconitic.com/paper/5ke7490e9z7jy.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:25:52Z",
      "native_id": "10.64898/2026.09.27.754856",
      "source": "biorxiv",
      "url": "https://www.biorxiv.org/content/10.64898/2026.09.27.754856v1"
    }
  ],
  "subjects": [
    {
      "field": "biology",
      "origin": "biorxiv:immunology",
      "subfield": "immunology"
    }
  ],
  "title": "A Tissue-Targeted Immunotherapy Protects Against Recurrent Ocular Herpes Infection and Disease, and Alleviates the Associated Cognitive, Behavioral, and Social Deficits in a 'Humanized' HLA Transgenic Mouse Model of UVB-Induced Reactivation",
  "title_text": "A Tissue-Targeted Immunotherapy Protects Against Recurrent Ocular Herpes Infection and Disease, and Alleviates the Associated Cognitive, Behavioral, and Social Deficits in a 'Humanized' HLA Transgenic Mouse Model of UVB-Induced Reactivation",
  "type": "preprint",
  "updated_at": "2026-10-30T12:25:52Z",
  "url": "https://research.draconitic.com/paper/5ke7490e9z7jy",
  "venue": "bioRxiv",
  "versions": []
}