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

Andrew T Jones,Korey L Walter,Pamela A Kozlowski,Linda S Wyatt,John D Clements,Dan H Barouch,David C Montefiori,Rama Rao Amara,Xiaoying Shen,Bernard Moss,Raghavan Varadarajan,Georgia D Tomaras,Celia C Labranche

doi:10.1038/s41467-019-08739-4

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.

Highlights

The oral mucosa is an attractive site for mucosal vaccination, the thick squamous epithelium limits antigen uptake
Needle-free sublingual and buccal (SL/B) and intradermal/subcutaneous route (ID/SC) immunization both results in a significant delay in acquisition of infection compared to unvaccinated controls, with non-neutralizing antibody effector functionality and Env-specific CD4 T-cell responses being the predominant correlates of protection
We detected conventional BDCA1+ myeloid dendritic cells (CD14−CD16−CD123−BDCA1+), but only low levels of plasmacytoid dendritic cells (CD14−CD16−CD123+BDCA1−) which may only be present during inflammation[8]

Summary

Introduction

The oral mucosa is an attractive site for mucosal vaccination, the thick squamous epithelium limits antigen uptake. Delay of infection correlates with non-neutralizing antibody effector function, Envspecific CD4+ T-cell responses, and gp[120] V2 loop specific antibodies These results demonstrate needle-free MVA/gp[120] oral vaccination as a practical and effective route to induce protective immunity against HIV-1. Needle-free SL/B and ID/SC immunization both results in a significant delay in acquisition of infection compared to unvaccinated controls, with non-neutralizing antibody effector functionality and Env-specific CD4 T-cell responses being the predominant correlates of protection. These results demonstrate that oral needle-free delivery of MVA-HIV/cycPgp[120] vaccination induces a strong antibody response in mucosal and systemic compartments with protective potential against HIV-1. They describe a novel method of needle-free vaccination that is practical and induces a strong antibody response in three major mucosal sites and serum

Methods

Results

Conclusion