Dr Laura McCoy
MRC Career Development Fellow
Research in the McCoy lab within the Division of Infection and Immunity at UCL focuses on the role of B cell biology in HIV infection and vaccine responses.
- 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 NetworkThis 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.
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.
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].
- Voss JE, Andrabi R, McCoy LE, de Val N, Fuller RP, Messmer T, Su CY, Sok D, Khan SN, Garces F, Pritchard LK, Wyatt RT, Ward AB, Crispin M, Wilson IA, Burton DR. Elicitation of Neutralizing Antibodies Targeting the V2 Apex of the HIV Envelope Trimer in a Wild-Type Animal Model. Cell Rep. 2017;21:222-235
- Pauthner M, Havenar-Daughton C, Sok D, Nkolola JP, Bastidas R, Boopathy AV, Carnathan DG, Chandrashekar A, Cirelli KM, Cottrell CA, Eroshkin AM, Guenaga J, Kaushik K, Kulp DW, Liu J, McCoy LE, Oom AL, Ozorowski G, Post KW, Sharma SK, Steichen JM, de Taeye SW, Tokatlian T, Torrents de la Peña A, Butera ST, LaBranche CC, Montefiori DC, Silvestri G, Wilson IA, Irvine DJ, Sanders RW, Schief WR, Ward AB, Wyatt RT, Barouch DH, Crotty S, Burton DR. Elicitation of Robust Tier 2 Neutralizing Antibody Responses in Nonhuman Primates by HIV Envelope Trimer Immunization Using Optimized Approaches. Immunity. 2017;46:1073-1088.e6
- Gray ER, Brookes JC, Caillat C, Turbé V, Webb BLJ, Granger LA, Miller BS, McCoy LE, El Khattabi M, Verrips CT, Weiss RA, Duffy DM, Weissenhorn W, McKendry RA. Unravelling the Molecular Basis of High Affinity Nanobodies against HIV p24: In Vitro Functional, Structural, and in Silico Insights. ACS Infect Dis. 2017;3:479-491
- McCoy LE, McKnight Á. Lessons learned from humoral responses of HIV patients. Curr Opin HIV AIDS. 2017;12:195-202
- McCoy LE, Burton DR. Identification and specificity of broadly neutralizing antibodies against HIV. Immunol Rev. 2017;275:11-20
- Steichen JM, Kulp DW, Tokatlian T, Escolano A, Dosenovic P, Stanfield RL, McCoy LE, Ozorowski G, Hu X, Kalyuzhniy O, Briney B, Schiffner T, Garces F, Freund NT, Gitlin AD, Menis S, Georgeson E, Kubitz M, Adachi Y, Jones M, Mutafyan AA, Yun DS, Mayer CT, Ward AB, Burton DR, Wilson IA, Irvine DJ, Nussenzweig MC, Schief WR. HIV Vaccine Design to Target Germline Precursors of Glycan-Dependent Broadly Neutralizing Antibodies. Immunity. 2016;45:483-496
- McCoy LE, van Gils MJ, Ozorowski G, Messmer T, Briney B, Voss JE, Kulp DW, Macauley MS, Sok D, Pauthner M, Menis S, Cottrell CA, Torres JL, Hsueh J, Schief WR, Wilson IA, Ward AB, Sanders RW, Burton DR. Holes in the Glycan Shield of the Native HIV Envelope Are a Target of Trimer-Elicited Neutralizing Antibodies. Cell Rep. 2016;16:2327-38
- Andrabi R, Voss JE, Liang CH, Briney B, McCoy LE, Wu CY, Wong CH, Poignard P, Burton DR. Identification of Common Features in Prototype Broadly Neutralizing Antibodies to HIV Envelope V2 Apex to Facilitate Vaccine Design. Immunity. 2015;43:959-73
- McCoy LE, Falkowska E, Doores KJ, Le K, Sok D, van Gils MJ, Euler Z, Burger JA, Seaman MS, Sanders RW, Schuitemaker H, Poignard P, Wrin T, Burton DR. Incomplete Neutralization and Deviation from Sigmoidal Neutralization Curves for HIV Broadly Neutralizing Monoclonal Antibodies. PLoS Pathog. 2015;11:e1005110.
A full list of publications can be accessed via PubMed.