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HIV-1 vaccination by needle-free oral injection induces strong mucosal immunity and protects against SHIV challenge

Author

Listed:
  • Andrew T. Jones

    (Emory University
    Emory University)

  • Xiaoying Shen

    (Duke University Medical Center)

  • Korey L. Walter

    (Louisiana State University Health Sciences Center)

  • Celia C. LaBranche

    (Duke University Medical Center)

  • Linda S. Wyatt

    (National Institutes of Health)

  • Georgia D. Tomaras

    (Duke University Medical Center)

  • David C. Montefiori

    (Duke University Medical Center)

  • Bernard Moss

    (National Institutes of Health)

  • Dan H. Barouch

    (Center for Virology and Vaccine Research, Beth Israel Deaconess Medical Center, Harvard Medical School)

  • John D. Clements

    (Tulane University School of Medicine)

  • Pamela A. Kozlowski

    (Louisiana State University Health Sciences Center)

  • Raghavan Varadarajan

    (Molecular Biophysics Unit, Indian Institute of Science)

  • Rama Rao Amara

    (Emory University
    Emory University)

Abstract

The oral mucosa is an attractive site for mucosal vaccination, however the thick squamous epithelium limits antigen uptake. Here we utilize a modified needle-free injector to deliver immunizations to the sublingual and buccal (SL/B) tissue of rhesus macaques. Needle-free SL/B vaccination with modified vaccinia Ankara (MVA) and a recombinant trimeric gp120 protein generates strong vaccine-specific IgG responses in serum as well as vaginal, rectal and salivary secretions. Vaccine-induced IgG responses show a remarkable breadth against gp70-V1V2 sequences from multiple clades of HIV-1. In contrast, topical SL/B immunizations generates minimal IgG responses. Following six intrarectal pathogenic SHIV-SF162P3 challenges, needle-free but not topical immunization results in a significant delay of acquisition of infection. Delay of infection correlates with non-neutralizing antibody effector function, Env-specific CD4+ T-cell responses, and gp120 V2 loop specific antibodies. These results demonstrate needle-free MVA/gp120 oral vaccination as a practical and effective route to induce protective immunity against HIV-1.

Suggested Citation

  • Andrew T. Jones & Xiaoying Shen & Korey L. Walter & Celia C. LaBranche & Linda S. Wyatt & Georgia D. Tomaras & David C. Montefiori & Bernard Moss & Dan H. Barouch & John D. Clements & Pamela A. Kozlow, 2019. "HIV-1 vaccination by needle-free oral injection induces strong mucosal immunity and protects against SHIV challenge," Nature Communications, Nature, vol. 10(1), pages 1-14, December.
    • Handle: RePEc:nat:natcom:v:10:y:2019:i:1:d:10.1038_s41467-019-08739-4
    DOI: 10.1038/s41467-019-08739-4
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    Cited by:

    1. Jeffy G. Mattathil & Asisa Volz & Olusegun O. Onabajo & Sean Maynard & Sandra L. Bixler & Xiaoying X. Shen & Diego Vargas-Inchaustegui & Marjorie Robert-Guroff & Celia Lebranche & Georgia Tomaras & Da, 2023. "Direct intranodal tonsil vaccination with modified vaccinia Ankara vaccine protects macaques from highly pathogenic SIVmac251," Nature Communications, Nature, vol. 14(1), pages 1-15, December.
    2. Venkata S. Bollimpelli & Pradeep B. J Reddy & Sailaja Gangadhara & Tysheena P. Charles & Samantha L. Burton & Gregory K. Tharp & Tiffany M. Styles & Celia C. Labranche & Justin C. Smith & Amit A. Upad, 2023. "Intradermal but not intramuscular modified vaccinia Ankara immunizations protect against intravaginal tier2 simian-human immunodeficiency virus challenges in female macaques," Nature Communications, Nature, vol. 14(1), pages 1-16, December.

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