MRC Career Development Fellow
B cell biology in HIV infection and vaccine responses.
Dr Laura McCoy completed her undergraduate studies in Biochemistry at the University of Oxford, UK in 2004 and received her PhD degree in 2010 from Imperial College London, UK, after studying Vaccinia virus with Prof Geoffrey L. Smith. She then joined the laboratory of Prof Robin Weiss at UCL as a postdoctoral researcher. In 2013 Laura was awarded a UCL/MRC Centenary Travel Award to support her move to The Scripps Research Institute in California to continue her postdoctoral research into HIV antibodies under the supervision of Prof Dennis R Burton.
In 2014 she was awarded a European Union Marie Curie International Outgoing Fellowship to continue her work on HIV vaccines in the Burton Lab until 2016 when she returned to UCL to establish her own research group. During 2017 she completed a 6-month UCL/MRC Proximity to Discovery secondment at GlaxoSmithKline in the Biopharmaceutical Molecular Discovery department.
- MRC Career Development Award project entitled "Investigating antibody affinity maturation during B cell exhaustion in viral infection"
This 5-year research fellowship aims to understand the role of dysfunction in B cells on the production of anti-viral antibodies during untreated HIV infection. This study uses two ongoing clinical cohorts based at UCL with collaborators Dr D Peppa and Prof R Gupta
- ERC Starting Grant project entitled "Understanding HIV-specific B cell function and viral immunogenicity"
This project grant is designed to understand whether aberrations in B cell function explain why only a few rare individuals make broadly neutralising antibodies. Previously collected samples from these individuals are under investigation to identify any changes in cellular regulation, or activation, in the B cells making antibodies that bind broadly neutralising epitopes. Key collaborators include Prof A McKnight at QMUL, Dr P Tolar at The Francis Crick Institute and Prof R Shattock at Imperial College London
- Member of the EPIICAL Network
This is an experimental and clinical platform for the early identification of novel therapeutic strategies for HIV infected children. Dr McCoy contributes to the virology work package led by Dr E Nastouli at UCLH
- Associate member Crick Institute Immunology Interest Group.
During her postdoctoral work at The Scripps Research Institute, Laura developed a system to isolate monoclonal antibodies following experimental immunisation which revealed that the holes in the glycan shield of HIV are the target of much of the neutralising response to stabilised HIV envelope protein trimers. This work was published in 2016 and 2017 in Cell Reports [PMID: 27545891; PMID: 28978475] and in 2017 in Immunity [PMID: 28636956].
In addition, Laura helped to understand the interactions of broadly neutralising HIV antibodies produced during infection and how the early pre-cursors of these antibodies can be targeted. This work was published in 2015 in Immunity: [PMID: 26588781].
Also, during her time in the USA, Laura studied the phenomenon of incomplete neutralisation previously reported to occur for glycan-dependent HIV antibodies. She showed that all antibodies, regardless of epitope, can exhibit incomplete neutralisation in a strain-dependent manner. This work raised important questions regarding the level of intra-stain viral heterogeneity that needs to be represented in a vaccine and was published in PLoS Pathogens in 2015 [PMID: 26267277].
While working in the Weiss lab from 2010-2013, Laura isolated a broadly neutralising antibody from an immunised llama as part of a Bill & Melinda Gates Foundation funded collaboration with the group of Prof Theo Verrips in the Netherlands and Dr Mike Seaman at Harvard. Laura demonstrated that J3 neutralises 96% of strains including subtypes A, B, C, D, BC, AE, AG, AC, ACD, CD, and G. Following this, she developed a high-throughput robotic platform to isolate additional potent and broadly neutralising VHH. Like J3, these VHH also target the CD4-binding site but neutralise viruses which are resistant to J3, highlighting the diverse ways this conserved region is susceptible to antibodies. These findings have been published in the Journal of Experimental Medicine in 2012 [PMID: 22641382]; PLoS Pathogens in 2014 [PMID: 25522326]; and Retrovirology in 2014: [PMID: 25700025].
- Selected publications
- Ng KW, Faulkner N, Cornish GH, et al.* Preexisting and de novo humoral immunity to SARS-CoV-2 in humans. Science. 2020;370(6522):1339-1343
- O'Nions J, Muir L, Zheng J, et al.* SARS-CoV-2 antibody responses in patients with acute leukaemia. Leukemia. 2021;35(1):289-292
- Houlihan CF, Vora N, Byrne T, et al. Pandemic peak SARS-CoV-2 infection and seroconversion rates in London frontline health-care workers. Lancet. 2020;396(10246):e6-e7
- Gupta RK, Peppa D, Hill AL, et al. Evidence for HIV-1 cure after CCR5Δ32/Δ32 allogeneic haemopoietic stem-cell transplantation 30 months post analytical treatment interruption: a case report. Lancet HIV. 2020;7(5):e340-e347
- Gupta RK, Abdul-Jawad S, McCoy LE, et al. HIV-1 remission following CCR5Δ32/Δ32 haematopoietic stem-cell transplantation. Nature. 2019;568(7751):244-248
- Voss JE, Gonzalez-Martin A, Andrabi R, et al. Reprogramming the antigen specificity of B cells using genome-editing technologies. Elife. 2019;8:e42995
- Bianchi M, Turner HL, Nogal B, et al. Electron-Microscopy-Based Epitope Mapping Defines Specificities of Polyclonal Antibodies Elicited during HIV-1 BG505 Envelope Trimer Immunization. Immunity. 2018;49(2):288-300.e8
- Burton AR, Pallett LJ, McCoy LE, et al. Circulating and intrahepatic antiviral B cells are defective in hepatitis B. J Clin Invest. 2018;128(10):4588-4603
- McCoy LE*. The expanding array of HIV broadly neutralizing antibodies. Retrovirology. 2018;15(1):70
* Corresponding author
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