POST 01070E : BCG EFFICACY QUESTIONED

POST 01070E : BCG EFFICACY QUESTIONED 27 March 2007 ____________________________________ NOTE : Most of you will have picked up the error in the link to the article on the ethics of compulsory vaccination. It is not even the first time I make this same mistake, a "w" instead of an "e" in the word technet. My apologies! The correct link is thus : http://www.technet21.org/pdf_file/HPV-IntroEthics.pdf The following news will hopefully generate comments by experts. As the highly technical article to which it refers is very recent and copyrights-protected, it is impossible for the time being to circulate it free without risks. ____________________________________ BCG vaccine questionned Tuberculosis still kills two million people in the world each year. The vaccine however, developed in 1921, has evolved to the point that researchers now doubt its effectiveness. After a decade of research, scientists from France, England and Canada have just published a study on the issue. The document ("Genome plasticity of BCG and impact on vaccine efficacy" by Brosch et al.) is available online from the US National Academy of Sciences. (On a US$10/2-days pay basis). However, the free abstract is copied below and available at : http://www.pnas.org/cgi/content/abstract/0700869104v1 "We know that the vaccine is not as effective as wished, it has evolved and changed." explains Marcel Behr, associate professor at McGill University, the Canadian researcher in this study. Researchers have succeeded in mapping the genetic code of the Baccille Calmette-Guérin, at the origin of the vaccine. With the years, the vaccine has evolved and even degenerated in laboratories where it is produced. The result : clinical trials of the old days were conducted on a vaccine that no longer exists. "Vaccines administered to infants today have never been tested, it is not the same product anymore, says Professor Behr. All these vaccines are thus of unknown effectiveness" This may have a significant operational impact, especially if view of tuberculosis resurgence worldwide. To follow-up! ----------------------------- Genome plasticity of BCG and impact on vaccine efficacy by Roland Brosch *, Stephen V. Gordon , Thierry Garnier *, Karin Eiglmeier *, Wafa Frigui *, Philippe Valenti *, Sandrine Dos Santos *, Stéphanie Duthoy *, Céline Lacroix *, Carmen Garcia-Pelayo†, Jacqueline K. Inwald†, Paul Golby†, Javier Nu ez Garcia†, R. Glyn Hewinson†, Marcel A. Behr ¶, Michael A. Quail ||, Carol Churcher ||, Bart G. Barrell ||, Julian Parkhill ||, and Stewart T. Cole *,** *Unité de Génétique Moléculaire Bactérienne, Institut Pasteur, 28 Rue du Docteur Roux, 75724 Paris Cedex 15, France; †Veterinary Laboratories Agency, Woodham Lane, New Haw, Addlestone, Surrey KT15 3NB, United Kingdom; ¶McGill University Health Centre, Montreal, QC, Canada H3G 1A4; and ||The Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, Cambridge CB10 1SA, United Kingdom Communicated by G. Balakrish Nair, International Centre for Diarrhoeal Disease Research Bangladesh, Dhaka, Bangladesh, January 31, 2007 (received for review December 14, 2006) To understand the evolution, attenuation, and variable protective efficacy of bacillus Calmette-Guérin (BCG) vaccines, Mycobacterium bovis BCG Pasteur 1173P2 has been subjected to comparative genome and transcriptome analysis. The 4,374,522-bp genome contains 3,954 protein-coding genes, 58 of which are present in two copies as a result of two independent tandem duplications, DU1 and DU2. DU1 is restricted to BCG Pasteur, although four forms of DU2 exist; DU2-I is confined to early BCG vaccines, like BCG Japan, whereas DU2-III and DU2-IV occur in the late vaccines. The glycerol-3-phosphate dehydrogenase gene, glpD2, is one of only three genes common to all four DU2 variants, implying that BCG requires higher levels of this enzyme to grow on glycerol. Further amplification of the DU2 region is ongoing, even within vaccine preparations used to immunize humans. An evolutionary scheme for BCG vaccines was established by analyzing DU2 and other markers. Lesions in genes encoding -factors and pleiotropic transcriptional regulators, like PhoR and Crp, were also uncovered in various BCG strains; together with gene amplification, these affect gene expression levels, immunogenicity, and, possibly, protection against tuberculosis. Furthermore, the combined findings suggest that early BCG vaccines may even be superior to the later ones that are more widely used. Published online before print March 19, 2007 ; Proceedings of the National Academy of Sciences, USA ______________________________________________________________________________ All members of the TechNet21 e-Forum are invited to send comments on any posting or to use the forum to raise a new discussion or request technical information in relation to immunization services. 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