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

Jones, Andrew T and Shen, Xiaoying and Walter, Korey L and LaBranche, Celia C and Wyatt, Linda S and Tomaras, Georgia D and Montefiori, David C and Moss, Bernard and Barouch, Dan H and Clements, John D and Kozlowski, Pamela A and Varadarajan, Raghavan and Amara, Rama Rao (2019) HIV-1 vaccination by needle-free oral injection induces strong mucosal immunity and protects against SHIV challenge. In: NATURE COMMUNICATIONS, 10 .

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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.

Item Type:	Journal Article
Publication:	NATURE COMMUNICATIONS
Publisher:	NATURE PUBLISHING GROUP
Additional Information:	Copyright for this article belongs to Springer Nature Publishing AG.
Department/Centre:	Division of Biological Sciences > Molecular Biophysics Unit
Date Deposited:	20 Mar 2019 05:45
Last Modified:	20 Mar 2019 05:45
URI:	http://eprints.iisc.ac.in/id/eprint/61934

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