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The bacille Calmette-Guérin (BCG) vaccine protects against severe extrapulmonary forms of tuberculosis (TB) but does not adequately protect against pulmonary TB -- the most prevalent form of TB. This recombinant BCG, VPM1002, has been created in response and investigated for preventing pulmonary TB in newborns and TB recurrence in adults through post-exposure immunization. Currently, this recombinant vaccine has been found to be more efficacious and safer than BCG in preclinical studies. VPM1002 is a recombinant BCG vaccine candidate expressing listeriolysin and deficient in urease that is generated in the genetic background of BCG Prague as it has a better safety profile than some other BCG versions due to the lack of the RD2 genome segment. This vaccine’s urease C gene is replaced with the listeriolysin O encoding gene from Listeria monocytogenes. By reducing urease C, phagosome acidification can occur, promoting phagolysosome fusion while also providing the optimal low pH for listeriolysin O stability. VPM1002 facilitates mycobacterial antigens being released into the cytosol while also triggering autophagy, inflammasome activation, and apoptosis, because of antigens and bacterial DNA being released into the cytosol of the host cell due to Listeriolysin O expression in this vaccine. Mycobacterial antigen accessing the cytosol also improves antigen presentation. The ability for mycobacterial antigens to reach the cytosol is due to this vaccine being engineered to secrete Hly which perforates phagosomal membranes. Because Hly is only active at an acidic pH, similar to listeriolysin O, the deletion of urease C was also beneficial for Hly to have optimal bioactivity in the phagosome. As of August 2020, this vaccine is being tested for prophylaxis against COVID-19 in human clinical trials.
The bacille Calmette-Guérin (BCG) vaccine protects against severe extrapulmonary forms of tuberculosis (TB) but does not adequately protect against pulmonary TB -- the most prevalent form of TB. This recombinant BCG, VPM1002, has been created in response and investigated for preventing pulmonary TB in newborns and TB recurrence in adults through post-exposure immunization. Currently, this recombinant vaccine has been found to be more efficacious and safer than BCG in preclinical studies. VPM1002 is a recombinant BCG vaccine candidate expressing listeriolysin and deficient in urease that is generated in the genetic background of BCG Prague as it has a better safety profile than some other BCG versions due to the lack of the RD2 genome segment. This vaccine’s urease C gene is replaced with the listeriolysin O encoding gene from Listeria monocytogenes. By reducing urease C, phagosome acidification can occur, promoting phagolysosome fusion while also providing the optimal low pH for listeriolysin O stability. VPM1002 facilitates mycobacterial antigens being released into the cytosol while also triggering autophagy, inflammasome activation, and apoptosis, because of antigens and bacterial DNA being released into the cytosol of the host cell due to Listeriolysin O expression in this vaccine. Mycobacterial antigen accessing the cytosol also improves antigen presentation. The ability for mycobacterial antigens to reach the cytosol is due to this vaccine being engineered to secrete Hly which perforates phagosomal membranes. Because Hly is only active at an acidic pH, similar to listeriolysin O, the deletion of urease C was also beneficial for Hly to have optimal bioactivity in the phagosome. As of August 2020, this vaccine is being tested for prophylaxis against COVID-19 in human clinical trials.
