{
  "abstract": "Despite decades of HIV-1 vaccine development, the clonal and cellular determinants of durable vaccine-induced T cell memory remain incompletely understood. Here, we combined antigen-specific T cell receptor (TCR) identification, longitudinal TCR sequencing, and single-cell multi-omics to characterize Env- and Gag-specific memory precursor T cells elicited by the HIV Vaccine Trials Network (HVTN) 505 DNA prime-recombinant adenovirus serotype 5 (rAd5) boost (DNA/rAd5) vaccine regimen. We developed a generalizable high-throughput approach to identify HIV-1 Env- and Gag-specific TCRs and found distinct patterns of clonal expansion, persistence, and contribution to memory between Env- and Gag-specific CD8 T cell responses. The DNA prime and rAd5 boost differentially shaped these repertoires, with rAd5-induced clones contributing proportionally more to the Gag-specific than to the Env-specific memory precursor compartment. Single-cell immune profiling further revealed distinct memory precursor states, with Env-specific responses enriched for GZMBPRF1 cytotoxic effector-memory (EM) CD8 T cells and Gag-specific responses containing a larger cycling/proliferative population. Together, these findings demonstrate that heterologous DNA/rAd5 vaccination generates antigen-specific CD8 T cell memory with distinct clonal trajectories and cellular programs, providing new insights into how vaccine platform and antigen-specificity shape the durability and functional properties of HIV-1 specific cellular immunity.",
  "abstract_shown": true,
  "affiliations": [
    "Fred Hutchinson Cancer Center"
  ],
  "article_type": "New results",
  "arxiv": null,
  "author_total": 17,
  "authors": [
    {
      "name": "G. Xu"
    },
    {
      "name": "J. X. Yee"
    },
    {
      "name": "S. M. Ilcisin"
    },
    {
      "name": "S. N. Kaul"
    },
    {
      "name": "K. Mayer-Blackwell"
    },
    {
      "name": "E. Moelhman"
    },
    {
      "name": "D. R. Glass"
    },
    {
      "name": "A. A. Minervina"
    },
    {
      "name": "S. T. Karuna"
    },
    {
      "name": "M. E. Sobieszczyk"
    },
    {
      "name": "M. R. Hart"
    },
    {
      "name": "P. G. Thomas"
    },
    {
      "name": "P. J. Skene"
    },
    {
      "name": "S. C. De Rosa"
    },
    {
      "name": "M. J. McElrath"
    },
    {
      "name": "A. Fiore-Gartland"
    },
    {
      "affs": [
        0
      ],
      "name": "E. W. Newell"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/53fmsqk9wj3tr.bib",
  "cited_by": 0,
  "doi": "10.64898/2026.09.23.752815",
  "fulltext_url": "https://www.biorxiv.org/content/10.64898/2026.09.23.752815v1.full",
  "id": "53fmsqk9wj3tr",
  "issns": [],
  "landing_url": "https://www.biorxiv.org/content/10.64898/2026.09.23.752815v1",
  "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",
      "2406|HIV Research and Treatment"
    ]
  ],
  "openalex": "W7214775327",
  "pdf_url": "https://www.biorxiv.org/content/10.64898/2026.09.23.752815v1.full.pdf",
  "pmcid": null,
  "pmid": null,
  "published": "2026-09-23",
  "publisher": null,
  "ris": "https://research.draconitic.com/paper/53fmsqk9wj3tr.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:25:14Z",
      "native_id": "10.64898/2026.09.23.752815",
      "source": "biorxiv",
      "url": "https://www.biorxiv.org/content/10.64898/2026.09.23.752815v1"
    }
  ],
  "subjects": [
    {
      "field": "biology",
      "origin": "biorxiv:immunology",
      "subfield": "immunology"
    }
  ],
  "title": "HIV-1 prime-boost vaccination shapes distinct clonal trajectories and memory precursor states of Env- and Gag-specific T cells",
  "title_text": "HIV-1 prime-boost vaccination shapes distinct clonal trajectories and memory precursor states of Env- and Gag-specific T cells",
  "type": "preprint",
  "updated_at": "2026-10-30T12:25:14Z",
  "url": "https://research.draconitic.com/paper/53fmsqk9wj3tr",
  "venue": "bioRxiv",
  "versions": []
}