Malaria kills around 0.8 million individuals per annum, mostly in sub-Saharan Africa where 1 in 5 childhood deaths is associated with malaria. The disease is spread from one individual to another by the bite of a female Anopheles mosquito. Developing a vaccine against malaria has been difficult due to the ever changing nature of the parasite in terms of its genetic diversity and life-cycle (pre-erythrocytic stage, blood-stage and mosquito-stage). Malaria vaccine development at the Jenner Institute is divided into three main areas:
The programme of pre-clinical malaria vaccine development at Oxford has led to significant advances in the field of vectored vaccines. This work began with a primary interest in the induction of high level T cell responses against pre-erythrocytic liver-stage malaria antigens. This has now widened to also include high level antibody induction against the blood-stage and mosquito-stage using both viral vectored and protein-in-adjuvant vaccines.
The Jenner Institute was founded in November 2005 in partnership with the Institute for Animal Health. Our Institute focuses both on diseases of humans and livestock. One of the founding principles of the Institute is the exploitation of synergies in the development of human and veterinary vaccines whereby new vaccine approaches can be tested in parallel in different species.
The Jenner Institute Insectary at the Old Road Campus Research Building is used for the rearing of mosquitoes. Researchers then use these mosquitoes to test vaccines against malaria, a disease caused by Plasmodium parasites that are transmitted from one person to another by female Anopheles mosquitoes. Our colony of Anopheles stephensi mosquitoes are reared in state-of –the-art temperature and humidity controlled incubators. The female mosquito lays her eggs in water, where they hatch after a few days. These aquatic larvae feed and develop through four stages, or instars, before pupation and emergence into adulthood. It takes two weeks after hatching for the mosquitoes to become adults.
The mosquitoes are used to produce sporozoites, which grow inside the mosquito salivary gland and are infective to the vertebrate host. We use sporozoites to test vaccines targeting the liver and blood stages of malaria infection. If the vaccine is protective then we see reduced parasites in the blood in comparison to the unvaccinated controls.
The facility is also used to test transmission-blocking malaria vaccines that aim to halt the sexual development of the malaria parasite in the mosquito. For this we grow the male and female forms of the human malaria parasite in red blood cells, mix them with antibodies induced through vaccination, and feed the mixture to the mosquitoes using an artificial membrane feeder. In the mosquito midgut the male and female parasites join and fertilise to form a zygote which then develops into an oocyst. The mosquitoes are kept in highly secure cabinets for a week before they are dissected and checked for the development of parasites in the midgut. If the vaccine works then we don’t see any sporozoite producing oocysts in the midgut.