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: VAC068.
The transmission-blocking malaria clinical trial undertaken to-date is: VAC062 Phase Ia safety & immunogenicity of ChAd63-MVA Pfs25-IMX313 [NCT02532049].
Nikolaeva D, Illingworth JJ, Miura K, Alanine DG, Brian IJ, Li Y, Fyfe AJ, Da DF, Cohuet A, Long CA, Draper SJ, Biswas S. 2017. Functional characterization and comparison of Plasmodium falciparum proteins as targets of transmission-blocking antibodies. Mol Cell Proteomics, ePub. [Pubmed]
Leneghan DB, Miura K, Taylor IJ, Li Y, Jin J, Brune KD, Bachmann MF, Howarth M, Long CA, Biswas S. 2017. Nanoassembly routes stimulate conflicting antibody quantity and quality for transmission-blocking malaria vaccines. Sci Rep, 7, pp. 3811. [Pubmed]
Brune KD, Buldun C, Li Y, Taylor I, Brod F, Biswas S, Howarth M. 2017. Dual plug-and-display synthetic assembly using orthogonal reactive proteins for twin antigen immunization. Bioconjug Chem, 28, pp. 1544-1551. [Pubmed]
Brune KD, Leneghan DB, Brian IJ, Ishizuka AS, Bachmann MF, Draper SJ, Biswas S, Howarth M. 2016. Plug-and-Display: decoration of Virus-Like Particles via isopeptide bonds for modular immunization. Sci Rep, 6, pp. 19234. [Pubmed]
Li Y, Leneghan DB, Miura K, Nikolaeva D, Brian IJ, Dicks MD, Fyfe AJ, Zakutansky SE, de Cassan S, Long CA, Draper SJ, Hill AV, Hill F, Biswas S. 2016. Enhancing immunogenicity and transmission-blocking activity of malaria vaccines by fusing Pfs25 to IMX313 multimerization technology. Sci Rep, 6, pp. 18848. [Pubmed]
Nikolaeva D, Draper SJ, Biswas, S. 2015. Toward the development of effective transmission-blocking vaccines for malaria. Expert Rev Vaccines, 19, pp. 1-28. [Pubmed]
Kapulu MC, Da DF, Miura K, Li Y, Blagborough AM, Churcher TS, Nikolaeva D, Williams AR, Goodman AL, Sangare I, Turner AV, Cottingham MG, Nicosia A, Straschil U, Tsuboi T, Gilbert SC, Long CA, Sinden RE, Draper SJ, Hill AV, Cohuet A, Biswas S. 2015. Comparative assessment of transmission-blocking vaccine candidates against Plasmodium falciparum. Sci Rep, 5, pp. 11193. [Pubmed]
Williams AR, Zakutansky SE, Miura K, Dicks MD, Churcher TS, Jewell KE, Vaughan AM, Turner AV, Kapulu MC, Michel K, Long CA, Sinden RE, Hill AV, Draper SJ, Biswas S. 2013. Immunisation against a serine protease inhibitor reduces intensity of Plasmodium berghei infection in mosquitoes. Int J Parasitol, 43 (11), pp. 869-74. [Pubmed]
Goodman AL, Blagborough AM, Biswas S, Wu Y, Hill AV, Sinden RE, Draper SJ. 2011. A viral vectored prime-boost immunization regime targeting the malaria Pfs25 antigen induces transmission-blocking activity. PLoS One, 6 (12), pp. e29428. [Pubmed]