Evaluating the use of nanoparticles as an antigen delivery system

The delivery of antigens on degradable nanoparticles, directly to dendritic cells residing in lymph nodes, offers great opportunities for vaccine design. This master thesis investigates the issues related to the development of vaccines based on ultrasmall (25nm)nanoparticles, capable of draining to lymph nodes via lymphatic flow and to spontaneously activate complement factor C3 as an adjuvant. The first part investigates a Mycobacterium tuberculosis preventive vaccine in collaboration with Northwestern (Jamie Carter and Garrett Green) and EPFL students (Marie Ballester and Bastien Schyrr) in Cape Town. Research plan for the preclinical testing of potential vaccine formulations to be used as a tuberculosis vaccine was investigated as well as adjuvancy, antigen dosage determination, efficacy, safety testing, vaccine manufacture, regulatory issues, and transition to clinical trials. In the second part, a peptide derived from the Apical Membrane Antigen 1 (AMA1) of the malaria causing parasite Plasmodium falciparum, conjugated to 28nm nanoparticles was used to immunize mice and proved to create an immune response in 4 out of 11 mice after 4 injections. Antibodies produced by the responding mice were able to recognize the native antigen on the parasite in Indirect Immunofluorescence and Western blotting Assays. The nanoparticles were retrieved in mice lymph nodes by Immunohistochemistry and were located near antigen presenting cells