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

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. Kozlowski, Raghavan Varadarajan and Rama Rao Amara ()
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Andrew T. Jones: 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

Nature Communications, 2019, vol. 10, issue 1, 1-14

Abstract: 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.

Date: 2019
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DOI: 10.1038/s41467-019-08739-4

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