Making vaccines work in the liver

A novel prime and target vaccination approach for malaria and liver diseases 

The induction of pathogenspecific cytotoxic CD8+ T-cells is important for protection against a number of intracellular pathogens, such as Plasmodium species causingmalaria, Human Immunodeficiency Virus (HIV), Mycobacterium tuberculosis (Tb) and Leishmania. Importantly, vaccines against these diseases have been particularly hard to develop, with few approaches able to generate and maintain a high protective CD8+ T-cell response.

Over the past 20 years, researchers at the Jenner Institute have been developing a strong platform of heterologous prime-boost vaccine regimens, utilizing recombinant adenoviruses and modified vaccinia Ankara (MVA) expressing several malaria proteins. These have shown significant but suboptimal  protection at the liver stage of the parasite’s development both in pre-clinical animal models and in human clinical trials.In the recent years, there has been an increased appreciation of tissue-specific immune responses.

Specifically, cytotoxic CD8+ T-cells have been shown to increase protection against mucosal and skin pathogens. Researchers at the Jenner Institute have now developed a new vaccination approach which can target protective CD8+ T-cells to the required organ or tissue, especially the liver. This is currently being developed for vaccination against malaria and hepatitis viruses. The prime and target vaccination strategy, in initial studies, has been shown to provide a significant improvement in vaccine efficacy over previous regimens, and underscores the importance of tailoring vaccine design to produce tissuespecific and localized pathogen-specific immune responses.

This new prime and target vaccination approach, utilizing heterologous vaccination routes with viral vectors or nanoparticles, has resulted in unprecedented protection in pre-clinical models of malaria infection and will soon be translated to clinical trials.