A study carried out on mice models has found that curcumin in nanoparticle form has the potential to enhance the efficacy of BCG vaccine such that it confers protection against adult pulmonary TB. The researchers found that injecting curcumin nanoparticles soon after vaccinating the mice with BCG produced an appreciable enhancement of immune memory cells (T central memory cells) responsible for long-term protection against TB infection.
BCG vaccine is effective against disseminated and meningeal TB in young children. But the protection does not last for long as the host-protective immune responses that the vaccine induces diminishes over time. Thus the vaccine is not protective in adults.
The team led by Gobardhan Das and Anand Ranganathan from the Special Centre for Molecular Medicine at the Jawaharlal Nehru University (JNU) demonstrated in mice models that curcumin nanoparticles enhance vaccine efficacy in two important ways. The work was done in collaboration with KIIT University, Bhubaneswar. The results were published in the journal Infection and Immunity.
In children, the vaccine induces two types of immune cells — effector memory T cells and central memory T cells. While the effector memory T cells play a crucial role in mounting an immediate immune response against virulent TB bacteria and kill them, the central memory T cells help in long-term protection in children from childhood TB. After persisting for some time, the central memory cells ultimately diminish. As a result, the protection does not last beyond childhood and adults become vulnerable to TB infection despite BCG vaccination.
One way of enhancing the efficacy of the BCG vaccine is by increasing the number of central memory cells so they last longer and confer protection for longer duration. In nature, dynamic balance exists between the two types of immune T cells — central memory cells and effector memory cells. Altering the ratio to increase the number of central memory cells will help in enhancing the efficacy of the BCG vaccine. “We were able to enhance the ratio of these two cell types by using curcumin nanoparticles,” says Prof. Das.
More memory cells
Increasing the number of central memory cells with respect to the effector memory cells was achieved through a simple process. The potassium ion channel (Kv1.3) is required for the differentiation of central memory cells into effector memory T cells. “In mice, the nanocurcumin blocks this channel and as a result the conversion of central memory cells into effector memory cells is under check. So the number of central memory cells increases leading to better vaccine efficacy,” says Shaheer Ahmad from JNU, the first author of the paper.
Curcumin also helps in the activation of innate immune cells known as macrophages and dendritic cells. TB bacteria reside and grow inside the macrophages. But once activated by curcumin nanoparticles, the macrophages and dendritic cells clear the bacteria and also enhance the level of TB-specific acquired immune cells (Th1 and Th17 cells).
“Curcumin nanoparticles not only increase the level of TB-specific acquired immune cells Th1 and Th17 but also simultaneously reduce the level of certain other cells (Th2 and Tregs) thus improving the efficacy of the BCG vaccine,” says Prof. Das. After TB infection, the levels of Th2 and Tregs cells increase and they inhibit the host-protective effect of Th1 and Th17 responses. So blocking or reducing the level of Th2 and Tregs cells enhances the vaccine efficacy.
The capacity of curcumin nanoparticles to modulate vaccine efficacy was tested in mice model. Following vaccination, the mice were treated with curcumin nanoparticles and then infected with TB bacteria. “We measured the bacterial burden in the lungs and spleen several times and observed that mice treated with curcumin nanoparticles had much less bacterial load than the controls,” says Ahmad.
“We are quite excited by this result and are hopeful further studies would take it to a stage where its application becomes a reality,” says Prof. Ranganathan.