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

Nat Commun. 2019 Feb 18;10(1):798. 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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • AIDS Vaccines / administration & dosage*
  • AIDS Vaccines / immunology
  • Administration, Oral*
  • Administration, Sublingual
  • Animals
  • Dendritic Cells / immunology
  • Female
  • HIV Envelope Protein gp120 / genetics
  • HIV-1 / pathogenicity
  • Immunity, Mucosal*
  • Immunoglobulin A / immunology
  • Immunoglobulin G / immunology
  • Injections / instrumentation
  • Injections / methods
  • Macaca mulatta
  • Needles
  • Simian Immunodeficiency Virus / pathogenicity
  • T-Lymphocytes / immunology
  • Vaccination / instrumentation
  • Vaccination / methods*
  • Vaccines, DNA / administration & dosage

Substances

  • AIDS Vaccines
  • HIV Envelope Protein gp120
  • Immunoglobulin A
  • Immunoglobulin G
  • Vaccines, DNA
  • gp120 protein, Human immunodeficiency virus 1