Stanisic Group

Supervisors: Dr Danielle Stanisic & Prof Michael Good

Parasitology, Immunology, Vaccinology

Babesiosis is a tick-borne infectious disease, caused by parasites of the genus Babesia.   Human babesiosis is typically asymptomatic, or results in mild symptoms that resolve within a few days in healthy individuals.  However, Babesia infection in the very young, the elderly, splenectomized, and immunocompromised individuals can result in acute anemia, multi-organ failure, or death. There is currently no human vaccine available, with prevention strategies focused on controlling the tick vector.  Babesia parasites also infect cattle, with bovine babesiosis (or cattle tick fever) having a major economic impact on the livestock industry in South America, Africa, Asia and Australia.   The currently used live attenuated cattle vaccine has a number of major drawbacks.

We have previously shown that a whole blood-stage parasite liposomal malaria vaccine is able to induce protective immunity in rodent models of the related Apicomplexan parasite, Plasmodium. This vaccine approach has been shown to induce a broad protective immunity. We have recently applied this same approach to the development of a Babesia vaccine, using a rodent model of B. microti. Further work is required to optimise the vaccine formulation to both maximise protective efficacy and to enable the development of a product that is compatible with administration to humans and cattle.  In this project, different vaccine candidates will be generated containing the whole Babesia parasite. For some vaccine candidates, recombinant proteins/peptides derived from the parasite will also be included.  Pre-clinical development of these vaccine candidates will include characterisation, optimisation and evaluation of the vaccine formulations.

Techniques: Parasitology, Vaccinology, Real-Time PCR, Cellular and Humoral Immunology (including Cell Culture, ELISA, Flow Cytometry and Cytokine Analyses).

Supervisors: Dr Danielle Stanisic & Prof Michael Good

Parasitology, Immunology, Vaccinology, Drug Discovery

Malaria is a parasitic disease prevalent in many developing countries, with transmission reported in 90 countries.  It is associated with extensive morbidity and mortality, mainly in pregnant women and young children. Currently available control strategies are becoming increasingly less effective; therefore the development of an effective vaccine is considered to be of critical importance. Many researchers have focused on single parasite-derived proteins in their quest to develop a sub-unit vaccine against malaria.  However, many of these proteins are highly variable, and are not useful in eliciting responses that can protect against multiple strains of the parasite.  A vaccine approach that uses the whole malaria parasite however, would contain multiple parasite antigens including antigens that are not altered by the parasite i.e. are therefore conserved between different parasite strains.

Using rodent models of malaria, it has previously been shown that different whole parasite asexual blood-stage vaccine approaches are able to induce species and strain-transcending protective immune responses.  One such approach is controlled infection immunization (CII).  This involves administering a malaria infection at the same time as anti-malarial treatment is commenced.  So far, these immunization regimens have required either multiple days of anti-malarial treatment (which is not viable for a vaccine strategy) or a single large dose of drug that is not currently clinically indicated in humans and may not be tolerated.  This may be overcome by using alternative anti-malarial drugs in the context of CII or by the use of slow release drug formulations

This project will involve further pre-clinical development and evaluation of the CII approach.  Using rodent models of malaria, pre-clinical development will initially involve characterising and optimising different anti-malarial drug formulations in the context of CII.  Their ability to control parasite growth will be examined.  If required, slow release drug formulations may be developed. The optimal drug formulations and parasite combinations will be evaluated for their ability to induce protection against subsequent challenge infection.  Immunological and functional assays will be used to assess immunogenicity and to examine the immune mechanisms of protection.  Results from this project will inform the transition of this vaccine approach into clinical studies.

Techniques: Parasitology, Vaccinology, Real-Time PCR, Cellular and Humoral Immunology (including Cell Culture, ELISA, Flow Cytometry and Cytokine Analyses).

Supervisors: Dr Danielle Stanisic & Prof Michael Good

Parasitology, Immunology, Vaccinology

Malaria is a global public health problem with transmission still being reported in over 90 countries.  It is an infectious disease caused by Plasmodium parasites which are transmitted by female Anopheline mosquitoes.  Current control methods are becoming increasingly less effective, therefore the development of an effective vaccine is considered to be of critical importance. The majority of malaria vaccine candidates are based on single malaria proteins, but many of these are highly variable and are not useful in inducing immune responses that will protect against multiple strains of the malaria parasite.

An alternate approach currently being developed, involves using the whole malaria parasite – such a vaccine contains multiple parasite proteins including those that are conserved between different parasite strains.

This study will involve the pre-clinical investigation of a Plasmodium falciparum transmission blocking liposomal vaccine.  This vaccine type does not prevent an individual from being infected like an asexual blood-stage vaccine aims to do, but rather stops an infected individual from transmitting malaria to other individuals.  This is because it targets the parasite life-cycle stage that is infective to mosquitoes.  It is thus seen as a community-based vaccine approach.

In this project, different vaccine candidates will be generated containing the P. falciparum gametocyte-stage parasite; this is the life-cycle stage that is found in the blood of malaria-infected individuals and is infective to mosquitoes.

For some vaccine candidates, recombinant proteins/peptides derived from the gamete-stage of the parasite, which is the stage of the parasite within the mosquito, will also be included.  Pre-clinical development of these vaccine candidates will include characterisation and optimisation of the vaccine formulations. Immunological and functional assays will also be undertaken to characterise the immunogenicity and transmission-blocking activity of the single and multi-component vaccine candidates ie whether the induced immune response impacts on parasite development and/or survival in the mosquito host.

Techniques: Parasitology, Vaccinology, Cellular and Humoral Immunology (including Cell Culture, ELISA, Flow Cytometry and Cytokine Analyses).