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Cambridge Infectious Diseases

An Interdisciplinary Research Centre at the University of Cambridge

Studying at Cambridge

 

Dr Andrew Blagborough

Dr Andrew Blagborough

Department of Pathology

Characterization of malarial transmission and the design of anti-parasitic transmission-blocking interventions


Biography:

Lecturer

Malaria transmission

After obtaining his degree in Biochemistry and Applied Clinical Biochemistry from UMIST in 2001, Andrew completed a PhD in Molecular Parasitology from the University of Manchester, studying the folate biosynthetic pathway of the malaria parasite Plasmodium falciparum. In 2006 he joined the Sinden lab at Imperial College, London, to study the sexual stages of Plasmodium, with an emphasis on developing transmission-blocking interventions (TBIs) to target the parasite within the mosquito host, inhibiting or preventing the onward transmission of malaria.  He is currently a Principal Investigator in the DoLS, and his main interests focus on the identification of novel anti-malarial transmission blocking vaccine targets, vaccine delivery, the development of assays to examine TBI efficacy, and assessing the practical impact of introducing TBIs on populations of mosquitoes and vertebrate in both the laboratory and the field.

My primary research can broadly be divided into three individual but complimentary streams:

1). Identification and characterisation of novel proteins expressed within the sexual stages of Plasmodium, i.e. the flagellate plasmodial gamete/ookinete, followed by examination by genetic/protein biochemical methods, and potentially, translation to novel transmission blocking interventions (TBI) candidates.

2). Effective delivery of TBIs to induce maximal efficacy. I am involved in the development of a wide range of novel vaccine delivery systems. With collaborators at Kanazawa University, I developed a novel dual-action baculovirus based vaccine system. This was adapted to constitute novel TBIs and pre-erythrocytic vaccines (PEVs). I am also involved with multiple prime-boost strategies to initiate effective responses, and in collaboration with researchers at the Fraunhofer Institute, USA, have developed a novel protein expression systemw to produce TBIs that have been characterized and evaluated for immunogenicity/efficacy in the lab and the field, demonstrating potent efficacy. I have also developed novel, potent whole parasite transmission blocking vaccines.

3). Enhanced, field-relevant assessment of TBI efficacy. TBIs aim to reduce the prevalence of infection in endemic communities by targeting Plasmodium within the mosquito, rather than directly inhibiting pathology. Whilst ‘traditional’ assays to assess blockade report reduction of infection in the mosquito, evidence of reduction in infection in the vertebrate host has previously been non-existent. We have developed a novel population transmission-based model to assess the impact of a TBI upon insect and vertebrate populations over multiple transmission cycles. Using this, wedemonstrated that partially effective TBIs can eliminate Plasmodium from populations at differing transmission intensities. These findings directly demonstrated for the first time that use of TBIs alone can eliminate Plasmodium from a vertebrate population, and have significant implications for the design and implementation of TBIs in the field. Specifically, the model allows for the extrapolation of lab-derived data to an estimated field context. This model is used to examine the transmission-blocking efficacy of a range of clinical/pre-clinical anti-malarial drugs, and vaccines.

Key Projects, Countries, and Partners

MRC Confidence in Concept award. “Development of native GPI anchored protein-based vaccines to drive malarial elimination and control”. 2018 – 2020. Principal Investigator.

Confidence in Concept award. “Development of a novel whole-parasite anti-malarial transmission-blocking vaccine”.

Award from PATH-MVI. Title = “Using a population transmission assay to evaluate waning anti-malarial vaccine efficacy and coverage”.

MRC New Investigator Research Grant (NIRG). “Dissecting the molecular basis for gamete recognition in the malaria parasite, and its targeting to block transmission”.

 

Departments and Institutes

Pathology:

Keywords

  • Mathematical Modelling
  • Vaccine development
  • Pathogen Evolution
  • Epidemiology
  • Drug Discovery

Topics

  • Plasmodium
  • Malaria

Equipment

  • Mathematical modelling

Key Publications

Delves MJ, Angrisano F, Blagborough M, 2018, Antimalarial Transmission-Blocking Interventions: Past, Present, and Future, Trends in Parasitology, Vol:34, ISSN:1471-4922, Pages:735-746

Esperanca PM, Blagborough AM, Da DF, et al., 2018, Detection of Plasmodium berghei infected Anopheles stephensi using near-infrared spectroscopy, Parasites and Vectors, Vol:11, ISSN:1756-3305

Sherrard-Smith E, Sala KA, Betancourt M, et al., 2018, Synergy in anti-malarial pre-erythrocytic and transmission-blocking antibodies is achieved by reducing parasite density, Elife, Vol:7, ISSN:2050-084X

Angrisano F, Blagborough AM, 2018, Understanding human-derived antibodies generated by polymorphic malaria vaccine against merozoite surface protein 2, Journal of Infectious Diseases, Vol:218, ISSN:0022-1899, Pages:5-6

Brugman VA, Kristan M, Gibbins MP, et al., 2018, Detection of malaria sporozoites expelled during mosquito sugar feeding., Scientific Reports, Vol:8, ISSN:2045-2322