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Nat Commun. 2019 Feb 18;10(1):798. doi: 10.1038/s41467-019-08739-4.

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

Author information

1
Emory Vaccine Center, Yerkes National Primate Research Center, Emory University, Atlanta, GA, 30329, USA.
2
Department of Microbiology and Immunology, Emory School of Medicine, Emory University, Atlanta, Georgia, 30329, USA.
3
Duke Human Vaccine Institute, Duke University Medical Center, Durham, NC, 27710, USA.
4
Department of Microbiology, Immunology and Parasitology, Louisiana State University Health Sciences Center, New Orleans, LA, 70112, USA.
5
Department of Surgery, Duke University Medical Center, Durham, NC, 27710, USA.
6
Laboratory of Viral Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, 20892, USA.
7
Center for Virology and Vaccine Research, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, 02115, USA.
8
Department of Microbiology and Immunology, Tulane University School of Medicine, New Orleans, LA, 8638, USA.
9
Molecular Biophysics Unit, Indian Institute of Science, Bangalore, 560012, India.
10
Emory Vaccine Center, Yerkes National Primate Research Center, Emory University, Atlanta, GA, 30329, USA. ramara@emory.edu.
11
Department of Microbiology and Immunology, Emory School of Medicine, Emory University, Atlanta, Georgia, 30329, USA. ramara@emory.edu.

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.

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