Currently, the only licensed vaccine against Mycobacterium tuberculosis (Mtb) is the attenuated strain, related to Mtb, known as BCG. While BCG protects some populations against some strains of Mtb, an improved vaccine for this deadly disease is needed. One recent effort to generate a better vaccine against Mtb is to engineer BCG to have improved immunogenicity in vaccinated individuals. BCG, like Mtb, infects macrophages, replicating in the macrophage phagosomes. Both BCG and Mtb prevent phagosome acidification and fusion with lysozomes, thereby preventing macrophages from efficiently killing the ingested bacteria. In addition, antigens from the bacteria are not found in the macrophage cytosol. To alter this lifestyle, BCG was engineered to express the listeriolysin protein from Listeria monocytogenes. This enzyme lyses the phagosomal membrane allowing antigens to escape into the cytosol. In addition, a mutation was generated in this same BCG to inactivate the bacterial urease, an enzyme that prevents acidification of phagosomes carrying ingested bacteria. This modified BCG was called rBCG, for recombinant BCG. To test whether rBCG induced more potent protection than the original vaccine strain, mice were immunized with BCG or rBCG, or left unimmunized, and then challenged with virulent Mtb. Titers of Mtb (CFU/lung) were then examined over time after challenge, as shown in Figure Q25). Figure Q25) Based on these data, rBCG likely induced: A) Increased cytolytic CD8 T cells capable of killing Mtb-infected macrophages B) Increased neutralizing antibody responses to Mtb C) Increased numbers of CD4 T_FH cells to Mtb peptides D) Increased activation of NK cells capable of killing Mtb-infected macrophages E) A decrease in the ability of Mtb to infect macrophages in the vaccinated mice

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The Answer of Currently, the only licensed vaccine against Mycobacterium tuberculosis (Mtb) is the attenuated strain, related to Mtb, known as BCG. While BCG protects some populations against some strains of Mtb, an improved vaccine for this deadly disease is needed. One recent effort to generate a better vaccine against Mtb is to engineer BCG to have improved immunogenicity in vaccinated individuals. BCG, like Mtb, infects macrophages, replicating in the macrophage phagosomes. Both BCG and Mtb prevent phagosome acidification and fusion with lysozomes, thereby preventing macrophages from efficiently killing the ingested bacteria. In addition, antigens from the bacteria are not found in the macrophage cytosol. To alter this lifestyle, BCG was engineered to express the listeriolysin protein from Listeria monocytogenes. This enzyme lyses the phagosomal membrane allowing antigens to escape into the cytosol. In addition, a mutation was generated in this same BCG to inactivate the bacterial urease, an enzyme that prevents acidification of phagosomes carrying ingested bacteria. This modified BCG was called rBCG, for recombinant BCG. To test whether rBCG induced more potent protection than the original vaccine strain, mice were immunized with BCG or rBCG, or left unimmunized, and then challenged with virulent Mtb. Titers of Mtb (CFU/lung) were then examined over time after challenge, as shown in Figure Q25). Figure Q25) Based on these data, rBCG likely induced: A) Increased cytolytic CD8 T cells capable of killing Mtb-infected macrophages B) Increased neutralizing antibody responses to Mtb C) Increased numbers of CD4 T_FH cells to Mtb peptides D) Increased activation of NK cells capable of killing Mtb-infected macrophages E) A decrease in the ability of Mtb to infect macrophages in the vaccinated mice

Currently, the Only Licensed Vaccine Against Mycobacterium Tuberculosis (Mtb) Is