Difference between revisions of "Team:CGU Taiwan/Background"

Background

1. Leishmania
2. Leishmania as a model organism
3. Basic Information of Adjuvant

Leishmania is a genus of trypanosomes protozoa that are responsible for leishmaniasis, a blood-borne disease spread by blood-sucking sandflies. Leishmania multiply and develop extracellularly as promastigotes in the digestive tract of the sandflies. When the female fly takes blood meals, the promastigotes are delivered into the skin of the mammalian host. They will directly infect macrophages, where they differentiate into amastigotes and multiply intracellularly as such.

Leishmania are aerobic organisms that rely on oxidative phosphorylation, but are defective in the synthesis of heme which is required for electron transport respiratory complexes. The genetic deficiency of heme biosynthesis in Leishmania makes it possible to produce transgenic DT mutants, which are inducible with delta-aminolevulinate (ALA) for accumulation of uroporphyrin I (URO) as a photosensitizer (PS).

Photosensitizers like uroporphyrin and aluminum phthalocyanine (PC) can be excited when illuminated at specific wavelengths and produce singlet oxygen and reactive oxygen species (ROS) to kill these parasitic protozoa (Oxidative inactivation).We adapted a combinational approach by loading the Leishmania DT mutants both endogenously with URO via the use of ALA and exogenously with PC. After URO and PC are illuminated by specific wavelength of light, double inactivation will kill Leishmania with proven effectiveness. Therefore, photo-inactivated Leishmania may be used as a carrier for delivery of antigen proteins to the antigen-presenting cells and induce humoral and cell-mediated immunity. This photodynamic Leishmania system provides us two major advantages to produce immunologic adjuvant.

First, it can be specifically recognized by antigen-presenting cells for delivery with higher efficiency. Second, the photo-inactivation of Leishmania provides the safety of this platform for vaccine delivery. These two advantages suggest that photo-inactivated Leishmania can be a novel system of immunologic adjuvant, leading to the next generation of vaccination.

Professor Kwang Poo Chang established this double-photo inactivation system of Leishmania and validated its role in modulating immune response.

Vaccine provides active adaptive immunity to a particular pathogen. Commonly used vaccines can be divided into four categories: attenuated, inactivated, sub-unit, and recombinant vaccines. Since inactivated, sub-unit and recombinant vaccines are often poorly immunogenic, additional components, aka adjuvant, are required to help stimulating antibody production and effector T cell functions. Immunologic adjuvants are compounds that can strongly activate both innate and adaptive immune system.

Adjuvants can be used for several purposes:

1. To enhance the immune responses of purified or recombinant antigens.
2. To reduce the amount of antigen or the number of immunizations needed for inducing protective immunity.
3. To improve the efficacy of vaccines for people with weaker immune responses, such as newborns, elders.

Adjuvants mediate their effects mainly through innate mechanism. When pathogens invade the human body, the innate immune system is first activated and responsible for the initial attack against the pathogens. Dendritic cells then act as antigen-presenting cells and migrate from infected tissue to regional lymph nodes to present the antigens to T cells. Adjuvants enhance the innate immune responses and create a bridge between innate and adaptive immunity to induce effective immunity.

The comparison of most commonly used commercial adjuvants Alum and MF59:

Alum is still the main adjuvant approved for human use worldwide. MF59 was widely used in influenza vaccines since the outbreak of the H1N1. No severe side effects were reported for MF59. However, MF59 is still under inspection due to lack of long-term analysis. Despite the success of current adjuvants, there is still a need for further improvement. Specifically, the challenge is to make adjuvant stimulating stronger T cell response and antibody production for protective immunity.