Recombinant BCG: Innovations on an Old Vaccine. Scope of BCG Strains and Strategies to Improve Long-Lasting Memory.

Adeliane Castro Da Costa,Ana Paula Junqueira-Kipnis,André Kipnis,Sarah Veloso Nogueira

doi:10.3389/fimmu.2014.00152

Adeliane Castro Da Costa, Ana Paula Junqueira-Kipnis + Show 2 more

Open Access

https://doi.org/10.3389/fimmu.2014.00152

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Journal: Frontiers in Immunologie	Publication Date: Jan 1, 2014
Citations: 64	License type: cc-by

Affiliation: Universidade Federal de Goiás

Abstract

Bacille Calmette–Guérin (BCG), an attenuated vaccine derived from Mycobacterium bovis, is the current vaccine of choice against tuberculosis (TB). Despite its protection against active TB in children, BCG has failed to protect adults against TB infection and active disease development, especially in developing countries where the disease is endemic. Currently, there is a significant effort toward the development of a new TB vaccine. This review article aims to address publications on recombinant BCG (rBCG) published in the last 5 years, to highlight the strategies used to develop rBCG, with a focus on the criteria used to improve immunological memory and protection compared with BCG. The literature review was done in April 2013, using the key words TB, rBCG vaccine, and memory. This review discusses the BCG strains and strategies currently used for the modification of BCG, including: overexpression of Mycobacterium tuberculosis (Mtb) immunodominant antigens already present in BCG; gene insertion of immunodominant antigens from Mtb absent in the BCG vaccine; combination of introduction and overexpression of genes that are lost during the attenuation process of BCG; BCG modifications for the induction of CD8+ T-cell immune responses and cytokines expressing rBCG. Among the vaccines discussed, VPM1002, also called rBCGΔureC:hly, is currently in human clinical trials. Much progress has been made in the effort to improve BCG, with some promising candidates, but considerable work is still required to address functional long-lasting memory.

Highlights

Tuberculosis (TB) is an infectious disease caused by Mycobacterium tuberculosis (Mtb), an intracellular pathogen that, after infecting a host, can cause disease or latency
PERSPECTIVES Bacille Calmette–Guérin has been used for almost 100 years, with more than eight million doses used
Two main cautions of Bacille Calmette–Guérin (BCG) vaccine use are associated with its variable efficacy and immunity against Mtb infection resulting in a large pool of latently/persistently infected individuals

Summary

Introduction

Tuberculosis (TB) is an infectious disease caused by Mycobacterium tuberculosis (Mtb), an intracellular pathogen that, after infecting a host, can cause disease or latency. During the BCG attenuation process and the years that followed, more than 14 sub-strains emerged: BCG Russia (ATCC 35740), BCG Moreau/Rio de Janeiro, BCG Tokyo, BCG Sweden, BCG Birkhaug (ATCC 35731), BCG Denmark 1331 (ATCC 35733), BCG China, BCG Prague, BCG Glaxo (ATCC 35741), BCG Tice (ATCC 35743), BCG Frappier (ATCC 35735), BCG Connaught, BCG Phipps (ATCC 35744), and BCG Pasteur 1173 [16]. They are distributed worldwide and have been used for vaccine development to prevent TB. The main concern is that BCG administration does not provide a reliable protection for adults in the developing world, protecting just against the main causes of infant TB, TB meningitis, and miliary TB [2]

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