Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Review
. 2014 Apr 7:5:152.
doi: 10.3389/fimmu.2014.00152. eCollection 2014.

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

Affiliations
Review

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

Adeliane Castro da Costa et al. Front Immunol. .

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.

Keywords: long-term memory; protection; rBCG; strain differences; tuberculosis; vaccine.

PubMed Disclaimer

References

    1. Kamath AT, Fruth U, Brennan MJ, Dobbelaer R, Hubrechts P, Ho MM, et al. New live mycobacterial vaccines: the Geneva consensus on essential steps towards clinical development. Vaccine (2005) 23(29):3753–61 10.1016/j.vaccine.2005.03.001 - DOI - PubMed
    1. World Health Organization (WHO) Global Tuberculosis Control–Epidemiology, Strategy, Financing. Geneva: WHO; (2009).
    1. World Health Organization Global Tuberculosis Control. Geneva: WHO; (1998).
    1. Partnership WST. The Global Plan to Stop TB 2011–2015: Transforming the Fight-Towards Elimination of Tuberculosis. Geneva: WHO; (2010).
    1. Aronson NF, Santosham M, Comstock GW, Haward RS, Moulton LH, Rhoades ER, et al. Long-term efficacy of BCG vaccine in American Indians and Alaska Natives: a 60-year follow-up study. JAMA (2004) 5:2086–91 10.1001/jama.291.17.2086 - DOI - PubMed