PubMed · 9402696
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K A De Smet. 1997. Mycobacterium tuberculosis: beyond genome sequencing.. https://doi.org/10.1016/s0966-842x(97)01132-3
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Development of vaccines has in many ways been the art of the possible, using current knowledge about infections and microbes to devise new products. The aim of every vaccination is to prevent disease, but use of vaccines within vaccination programs is usually targeted not only to protect the individual, but also to changing the epidemiology of the disease. Several new vaccines will become available during the next decade, but the vaccination program will probably not be dramatically changed. Increased knowledge about the immune system might, in a longer time perspective, make it possible to rebuild a vaccination program on a new basis. Immunisations can perhaps be used for targeting the immune system in ways that still give protection against the specific infections, but in addition lead to better health through general protection against diseases, less allergy and less autoimmune diseases than we have today.
Francisella tularensis is a bacterial pathogen that causes the zoonotic disease tularemia and is important to biodefense. Currently, the only vaccine known to confer protection against tularemia is a specific live vaccine strain (designated LVS) derived from a virulent isolate of Francisella tularensis subsp. holarctica. The origin and source of attenuation of this strain are not known. To assist with the design of a defined live vaccine strain, we sought to determine the genetic basis of the attenuation of LVS. This analysis relied primarily on the comparison between the genome of LVS and Francisella tularensis holarctica strain FSC200, which differ by only 0.08% of their nucleotide sequences. Under the assumption that the attenuation was due to a loss of function(s), only coding regions were examined in this comparison. To complement this analysis, the coding regions of two slightly more distantly related Francisella tularensis strains were also compared against the LVS coding regions. Thirty-five genes show unique sequence variations predicted to alter the protein sequence in LVS compared to the other Francisella tularensis strains. Due to these polymorphisms, the functions of 15 of these genes are very likely lost or impaired. Seven of these genes were demonstrated to be under stronger selective constraints, suggesting that they are the most probable to be the source of LVS attenuation and useful for a newly defined vaccine.
In spite of well-recognised differences in morbidity patterns among boys and girls, differences in their response to common interventions like vaccinations have rarely been considered. Our research in vaccinations and vitamin A supplementation has suggested sex differences in the response to these interventions. If these observations reflect a general pattern, it may be that, in order to be treated equally, boys and girls should be treated differently.