Malaria Programme: Transmission-Blocking Vaccines
The pre-clinical research in the transmission blocking groups focuses on antigen-screening of the leading transmission blocking vaccine candidates (both parasite and vector-based) using the viral vector vaccine platform. We are also investigating vaccines against novel target antigens that regulate the mosquito’s innate immune system. The innate immune response of the mosquito considerably hinders the development of the parasite, but this is often not sufficient to clear the infection.
In natural infection of the mosquito by Plasmodium malaria parasites, there has to be a fine balance between the immune response against the parasite and immune pathology which is reportedly detrimental to the survival of the mosquito. We are trying to tip this balance in favour of the immune response by inducing antibodies which neutralise regulatory molecules in the mosquito immune system. This will markedly hinder parasite development and reduce malaria transmission.
If successful, this novel strategy would not only work against potentially all five malaria parasite species that infect humans, but likely also against some other mosquito-transmitted diseases and could have a major impact in decreasing the burden of vector-borne diseases.
Working closely with the Blood-Stage Vaccines group, we also investigate ways to improve antibody immunogenicity and longevity induced by viral vectors.
Our main interests are:
1. Antigen-screening both parasite and vector based to define optimal combinations to block malaria transmission.
2. Dissect the mechanisms of vaccine-induced immunity against both parasite and vector based antigens.
3. Investigate new ways to improve magnitude and longevity of the antibody response induced by prime boost vaccination using candidate viral vectored and recombinant protein vaccines.
The promising new approaches and/or candidate vaccines will be taken forward to clinical trials.
Alongside basic research, there is a strong translational emphasis, with the most promising new approaches and/or candidate vaccines feeding into the Transmission-Blocking Malaria Clinical Trials Programme. Candidate vaccines are manufactured to current Good Manufacturing Practice (cGMP) at the Clinical BioManufacturing Facility, with Phase Ia trials subsequently being led from the Centre for Clinical Vaccinology and Tropical Medicine.
The latest Draper/Biswas group trials are recruiting here: VAC063C.
The transmission-blocking malaria clinical trial undertaken to-date is: VAC062 Phase Ia safety & immunogenicity of ChAd63-MVA Pfs25-IMX313 [NCT02532049].