Mtb H37Ra is very close to a pathogenic strain of mycobacterium. The H37Ra strain is non-pathogenic and also have good repertoire of proteins that are very close to pathogen. But, the strain failed to elicit immune response.
Please help me in understanding the requirement for generation of protective immune response !!!
Thank you Dear Lee and Arbind.. You have provided me a good clue that expression system "ESX" is very crucial for a successful TB vaccine.
Please also suggest me some more filters.
H37Ra is an avirulent MTB strain resembling the virulent strai. the ribosomal fraction settles during high speed centrifugation. in vivo activity in mice with and without freunds adjuvant has shown that the ribosomal or the membranous fractions , on their own are poorly immunogenic. probably a membranous fraction with adjuvant fraction may help you in eliciting immune response
While I agree with the comments above about loss of immunodominant antigens, a second factor to consider is that H37Ra grows poorly, if at all in mice, and compared to a similar innoculating dose of H37Rv induces very weak immune responses. This is not surprising, when you consider that H37Rv will increase in numbers many-fold over the first two weeks of infection, and that growth only slows down once a robust immune response is generated.
In other words, H37Rv keeps growing until it stimulates a good immune response - H37Ra does not: even SCID mice can control/eliminate it. Even BCG - which is itself highly attenuated - grows better You can get a good response with H37Ra in mice, but a much higher dose is required (doses 10-100x that of H37Rv are typically used).
This was the great to have response from the experts like Dr. T. M. Doherty. Dear Dr. Doherty, I am interested in the proteins responsible for differential behavior of growth between H37Rv and H37Ra. Because this could help us in relating the week immune response with H37Ra. Out of these proteins, this would be important to filter out the proteins involved directly in virulence.
I believe in this way, we can reach to a level for vaccine candidate that could be used in subunit vaccine and/or these proteins could be a part of recombinant BCG vaccine.
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