Investigators

James Binley, Ph.D.

Professor
HIV & Coronavirus Vaccine Development

Contact: jbinley@sdbri.org

James has spent his career working on the antibody response to HIV, with a particular interest in vaccine development. He began his career in 1991 at The Scripps Research Institute in La Jolla, CA, where he made phage displayed antibody libraries from HIV+ patient bone marrow. He then “panned” (selected) these libraries against various antigens to try to discover new broadly neutralizing monoclonal antibodies (bNAbs). These bNAbs are important for vaccine development, because they provide a blueprint for vaccines that aim to induce similar bNAbs to fend off infection. In 1995, James moved to the Aaron Diamond AIDS Research Center in New York City, where he became heavily involved in research on the impact of newly emerging highly active antiviral drug therapies that can reduce the levels of HIV in the blood of infected people to below detectable levels. Later, he moved to Cornell University, where he began working on an HIV vaccine to elicit bNAbs. By this time, it had become increasingly clear that bNAbs uniquely recognize the native form of the HIV spike protein, but most antibodies, including those induced by vaccines up to that point, could not bind effectively. Accordingly, it became increasingly clear that for vaccines to be effective, they would need to look more like native spikes.

Most HIV vaccine candidates are “subunit” in nature, in that they express the isolated spike protein only. The problem was that these isolated spikes were unstable. Recognizing this challenge, in 2000, James successfully designed stabilized mutant “SOS” spikes. This was a career highlight and a turning point in the HIV-1 vaccine field: James’ SOS mutation became the foundation or “spine” of hundreds of studies in the ensuing 20 years by James and others including a current phase I vaccine trial.

James returned to The Scripps Research Institute in 2001. In 2004, he became an Assistant Member at The Torrey Pines Institute. In 2015, he became a Founding Member at the San Diego Biomedical Research Institute. Over the last 20 years, James has largely been applying the SOS mutation to a virus-like particle (VLP) HIV vaccine platform, based on the premise that VLPs carry spikes that look exactly like those on the real virus (unlike subunit SOS spikes) – in essence, this is a Jennerian approach, based on the long history of particle-based vaccines. However, for HIV, the challenge is by no means straightforward. Not only do VLPs need to present native spikes, they must be able to induce antibodies to conserved parts of these spikes that are shared by different HIV strains. Only then can they induce bNAbs that can protect against any of the massively diverse strains that we might encounter. Accordingly, James is developing carefully modified VLPs and is now testing them in various models in an “in house” SDBRI collaboration with Dr Verkoczy. We hope that this will be the long awaited first step into a rational vaccine approach that can consistently induce bNAbs and which therefore could be a major step in halting this pandemic that has claimed the lives of an estimated 33M people over the last 30 years.

James has recently begun working on SARS-CoV-2 to understand the impact of pre-existing immunity to other coronaviruses and to try to make a universal coronavirus vaccine that might protect against other newly emerging coronaviruses. This might be compared to efforts to develop a universal flu vaccine to replace the annual (seasonal) vaccine.

Select Publications

Crooks ET, Grimley SL, Cully M, Osawa K, Dekkers G, Saunders K, Rämisch S, Menis S, Schief WR, Doria-Rose N, Haynes B, Murrell B, Cale EM, Pegu A, Mascola JR, Vidarsson G, Binley JM. Glycoengineering HIV-1 Env creates ‘supercharged’ and ‘hybrid’ glycans to increase neutralizing antibody potency, breadth and saturation. PLoS Pathog. 2018 May 2;14(5):e1007024. doi: 10.1371/journal.ppat.1007024. PMID: 29718999; PMCID: PMC5951585.

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Cale EM, Gorman J, Radakovich NA, Crooks ET, Osawa K, Tong T, Li J, Nagarajan R, Ozorowski G, Ambrozak DR, Asokan M, Bailer RT, Bennici AK, Chen X, Doria-Rose NA, Druz A, Feng Y, Joyce MG, Louder MK, O’Dell S, Oliver C, Pancera M, Connors M, Hope TJ, Kepler TB, Wyatt RT, Ward AB, Georgiev IS, Kwong PD, Mascola JR, Binley JM. Virus-like Particles Identify an HIV V1V2 Apex-Binding Neutralizing Antibody that Lacks a Protruding Loop. Immunity. 2017 46:777-791.

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Crooks ET, Osawa K, Tong T, Grimley SL, Dai YD, Whalen RG, Kulp DW, Menis S, Schief WR, Binley JM. Effects of partially dismantling the CD4 binding site glycan fence of HIV-1 Envelope glycoprotein trimers on neutralizing antibody induction. Virology. 2017 505:193-209.

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Kwon YD, Pancera M, Acharya P, Georgiev IS, Crooks ET, Gorman J, Joyce MG, Guttman M, Ma X, Narpala S, Soto C, Terry DS, Yang Y, Zhou T, Ahlsen G, Bailer RT, Chambers M, Chuang GY, Doria-Rose NA, Druz A, Hallen MA, Harned A, Kirys T, Louder MK, O’Dell S, Ofek G, Osawa K, Prabhakaran M, Sastry M, Stewart-Jones GB, Stuckey J, Thomas PV, Tittley T, Williams C, Zhang B, Zhao H, Zhou Z, Donald BR, Lee LK, Zolla-Pazner S, Baxa U, Schön A, Freire E, Shapiro L, Lee KK, Arthos J, Munro JB, Blanchard SC, Mothes W, Binley JM, McDermott AB, Mascola JR, Kwong PD. Crystal structure, conformational fixation and entry-related interactions of mature ligand-free HIV-1 Env. Nat Struct Mol Biol. 2015 Jul;22(7):522-31. doi: 10.1038/nsmb.3051. Epub 2015 Jun 22. PMID: 26098315; PMCID: PMC4706170.

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Crooks ET, Tong T, Chakrabarti B, Narayan K, Georgiev IS, Menis S, Huang X, Kulp D, Osawa K, Muranaka J, Stewart-Jones G, Destefano J, O’Dell S, LaBranche C, Robinson JE, Montefiori DC, McKee K, Du SX, Doria-Rose N, Kwong PD, Mascola JR, Zhu P, Schief WR, Wyatt RT, Whalen RG, Binley JM. Vaccine-Elicited Tier 2 HIV-1 Neutralizing Antibodies Bind to Quaternary Epitopes Involving Glycan-Deficient Patches Proximal to the CD4 Binding Site. PLoS Pathog. 2015 May 29;11(5):e1004932

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Cale EM, Doria-Rose NA, Tong T, Crooks ET, Nguyen R, Ambrozak DR, Perfetto SP, Roederer M, Binley JM, Mascola JR. Use of enzyme-digested virus-like particles as probes for flow cytometric sorting of HIV-specific neutralizing Ab-producing B-cells. AIDS Res Hum Retroviruses. 2014;30 Suppl 1:A20

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Tong T, Crooks ET, Osawa K, Robinson JE, Barnes M, Apetrei C, Binley JM. Multi-parameter exploration of HIV-1 virus-like particles as neutralizing antibody immunogens in guinea pigs, rabbits and macaques. Virology. 2014;456–457:55–69.

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All of Dr. James Binley’s Publications

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