Tuesday, 13 August 2013

BCG Vaccine Ineffectiveness

The current BCG vaccines are all derived from a strain of Mycobacterium bovis (M. bovis) that was isolated from the milk of a cow suffering from tuberculous mastitis and attenuated by 230 serial passages on potato-glycerin-ox bile medium - a medium composed essentially of cooked potatoes and glycerinated ox bile [1, 12].

The original strain of BCG, maintained at the Pasteur Institute in Lille, France, produced hundreds of "daughter" strains and became the progenitor of the most commonly used vaccines, the Danish strain, originating in 1931 as the 423rd transfer; the Tokyo strain, sent from France as a seed culture in 1925; and the Glaxo strain, derived from the 1077th transfer of the Danish strain. There is no conclusive evidence available to show which BCG strain offers better protection from TB in human. All different BCG strains differ in terms of their immunogenicity, efficacy and side effects [2].

Among the possible reasons for the ineffectiveness of the BCG vaccine in Malaysia:
  • Genetic variation in BCG strains - Early BCG vaccines may be more superior than the current ones, however it was also more virulent. Hence the need to passage the virus culture many times. Research has identified genome plasticity of BCG whereby tandem duplication of DU1 and DU2 occurred due to the M. bovis strain being grown on glycerinated potato slices, hence unknowingly imposing selective pressure for genetic alterations to this natural mutant for glycerol metabolism, so that glycerol could be used as a carbon and energy source [3]. The BCG strain has mutated over the years for survival in its culture environment and scientists are unable to control the mutation, resulting in a lack of control over the efficacy of the BCG vaccine [11].
  • Not specific to geographic region - Malaysia does not produce its own BCG vaccine, therefore the BCG strain that we use is based on whichever country or manufacturer we are importing it from [10]. 
  • Exposure to ultraviolet light - Ultraviolet light from the sun may affect the effectiveness of the BCG vaccine [4]. Perhaps this is due to the healing rays of Vitamin D which regulates the immune system and triggers the body's T cells to seek out and destroy any invading bacteria and viruses [7, 8, 9] . Malaysia's location near the equator gives us year-round sunlight.
  • Previous exposure to mycobacteria - Natural immunity to environmental mycobacteria interferes with the body's immune response to the vaccine [5]. Although exposure is common to environmental mycobacteria, disease is uncommon [6]. Most adults are exposed to environmental mycobacteria in developing countries, hence the reason BCG vaccine is given to babies with the hopes of stimulating an immune response..
  • Waning immunity - Protection offered by the BCG vaccine is not lifelong, if there is any immunity (efficacy ranges from 0% to 80%) from the vaccine, it is estimated to be around 10 years. [5] 
Read here for more info about the BCG' vaccine.

  1. The Art & Science of Tuberculosis Vaccine Development http://tbvaccines.usm.my/
  2. Joung, SM & Ryoo S (2013). BCG Vaccine In Korea. Clinical and Experimental Vaccine Research, 2(2), 83-91. doi: http://dx.doi.org/10.7774/cevr.2013.2.2.83 
  3. Genome plasticity of BCG and impact on vaccine efficacy http://www.pnas.org/content/104/13/5596.full.pdf
  4. Jeevan A, Sharma AK & McMurray DN (2009). Ultraviolet radiation reduces resistance to Mycobacterium tuberculosis infection in BCG-vaccinated guinea pigs. Tuberculosis, 89(6), 431-438. http://www.tuberculosisjournal.com/article/S1472-9792(09)00086-9/fulltext
  5. Tuberculosis and the BCG Vaccine: Not Good Enough http://www.scq.ubc.ca/tuberculosis-and-the-bcg-vaccine-not-quite-good-enough/
  6. Nontuberculous (Environmental) Mycobacterial Disease http://www.thoracic.org/education/breathing-in-america/resources/chapter-12-nontuberculous-mycobacterial-disease.pdf
  7. Vitamin D and Health http://www.hsph.harvard.edu/nutritionsource/vitamin-d/
  8. Vitamin D 'triggers and arms' the immune system http://www.telegraph.co.uk/health/healthnews/7379094/Vitamin-D-triggers-and-arms-the-immune-system.html
  9. Vitamin D and the Immune System http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3166406/
  10. BCG (Tuberculosis) http://www.who.int/biologicals/areas/vaccines/bcg/Tuberculosis/en/
  11. Brosch R, Gordon SV, Buchrieser C, Pym AS, Garnier T & Cole ST (2000). Comparative genomics uncovers large tandem chromosomal duplications in Mycobacterium bovis BCG Pasteur. Yeast, 17, 111-123. http://www.pasteur.fr/recherche/unites/Pmi/Dupli.PDF
  12. Liu J (2009). New vaccine against tuberculosis: Current developments and future challenges. Science Foundation in China, 17(2), 50-58. doi: 10.1088/1005-0841/17/2/006 

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