Targeting Unconventional Host Components for Vaccination-Induced Protection Against TB.

Elisa Nemes,Shabaana A Khader,Rosemary V Swanson,Willem A Hanekom

doi:10.3389/fimmu.2020.01452

Abstract

The current tuberculosis (TB) vaccine, Bacille Calmette-Guerin (BCG), is effective in preventing TB in young children but was developed without a basic understanding of human immunology. Most modern TB vaccine candidates have targeted CD4+ T cell responses, thought to be important for protection against TB disease, but not known to be sufficient or critical for protection. Advances in knowledge of host responses to TB afford opportunities for developing TB vaccines that target immune components not conventionally considered. Here, we describe the potential of targeting NK cells, innate immune training, B cells and antibodies, and Th17 cells in novel TB vaccine development. We also discuss attempts to target vaccine immunity specifically to the lung, the primary disease site in humans.

Highlights

One vaccine is currently licensed to prevent tuberculosis (TB), i.e., Bacillus Calmette-Guerin (BCG)
BCG’s protection against TB disease at older ages has been variable and mostly poor [1]; it was recently shown that BCG may have protective efficacy against Mycobacterium tuberculosis (Mtb) infection, as defined by sustained interferon-γ release assay (IGRA) conversion, in adolescents who had been IGRA negative at the time of vaccination [2]
A recent study employing a repeated limiting dose Mtb challenge model in rhesus macaques showed that mucosal BCG vaccination induced protective immune responses against both Mtb infection and TB disease, including Th1/Th17 and IL-10 responses, which were only observed in the lung and not in blood [72]

Summary

INTRODUCTION

One vaccine is currently licensed to prevent tuberculosis (TB), i.e., Bacillus Calmette-Guerin (BCG). While other innate lymphoid cells such as Group 3 ILCs have been recently implicated in protective immunity to TB [29], their role in vaccine-induced immunity is unknown and needs to be fully explored Taken together, these studies suggest that NK cells actively contribute to immune responses against Mtb, can be modulated by vaccination, and can be directed to respond to Mtb. While the mechanisms underlying these observations remain to be established, induction of NK responses by vaccination and their role in supporting and amplifying adaptive immunity during the early stages of Mtb infection and progression to TB disease deserve to be considered in immune correlates of protection studies built on recent efficacy trials of BCG [2] and M72 vaccines [5]. The specific application of this field to TB vaccine development has recently been reviewed [10]

B CELLS AND ANTIBODIES

CONCLUSIONS