Kwong-Shapiro Lab
Principal Investigators
The Kwong-Shapiro Lab focuses on structural vaccinology to advance antibody therapeutics and prophylactic vaccines. Their research on antibody interactions and pathogen entry mechanisms has contributed to the design of vaccines against HIV-1, influenza A, and RSV.
Our History
The Kwong-Shapiro Lab was conceived when Peter D. Kwong nd Lawrence Shapiro were graduate students in laboratory of Wayne A. Hendrickson in the Department of Biochemistry, Columbia University. They had worked together as students (e.g., Shapiro 1995 Nature), and between trips to the synchrotron and screenings of Burning Habits, hatched plans for a joint laboratory focusing on structural biology.
Lawrence Shapiro, PhD, became an assistant professor at Mount Sinai School of Medicine (1997-2001), before returning to Columbia as an Associate Professor and becoming a Professor in 2012. Kwong solved the structure of HIV-1 gp120 envelope glycoprotein, bound by the CD4 receptor and a neutralizing antibody in 1998 (Kwong 1998 Nature), then joined the Vaccine Research Center, NIAID, NIH, where he developed and used the precepts of antibody-guided structure-based vaccine to create vaccines. He developed a fusion peptide-based vaccine, which can elicit broadly neutralizing antibodies against HIV-1 in standard vaccine-test species, such as rhesus macaques (Kong 2019 Cell). While at the VRC, he also developed vaccines against other human pathogens including respiratory syncytial virus (RSV). For RSV, he led the design of a prefusion-stabilized variant of the RSV fusion glycoprotein called DS-Cav1 (McLellan 2013 Science), which GSK developed into the AREXVY vaccine, which received FDA approval in 2023.
Peter D. Kwong, PhD, returned to Columbia University in December 2023, as a Professor in Medicine and Co-Director of the Aaron Diamond AIDS Research Center and, together with Dr. Shapiro, formed the Kwong-Shapiro Lab, which uses structure determination as a primary research tool for investigations into:
- Antibodies,
- Entry machines,
- Structure-based vaccines.
Our Research
Structural Vaccinology To Develop Antibody Therapeutics and Prophylactic Vaccines
Structural biology allows access to the chemistry underlying biology interactions. With antibodies, structural tools can be used to develop probes for antibody identification and to visualize antibody in the act of recognizing antigen. With entry machines, these are crucial for many pathogens and often targets for neutralizing antibody.
With antibody-guided structure-based vaccines, we are combining analyses of antibodies and entry machines to develop vaccines against influenza A virus, HIV-1, and other human pathogens.
For influenza A virus, we recently identified a conserved lateral patch in the head region of hemagglutinin, which might serve as vaccine target (Jia 2024 Nature Communications). For HIV-1, we are continuing to use the tools of Antibodyomics (Kwong 2017 Immunological Reviews) to read-out elicited responses, including those from rhesus macaques. Recently, we have been working with George Shaw to assess simian-human chimeric viruses, modified by structure-based design (Li 2016 PNAS) for their ability to elicit broadly neutralizing responses (Roark 2021 Science) and (Wang 2024 Cell).
Lab Members
Select Publications
Jia M, Zhao H, Morano NC, Lu H, Lui YM, Du H, Becker JE, Yuen KY, Ho DD, Kwong PD, Shapiro L, To KK, Wu X. Human neutralizing antibodies target a conserved lateral patch on H7N9 hemagglutinin head. Nat Commun. 2024 May 27;15(1):4505. doi: 10.1038/s41467-024-48758-4.PMID: 38802413
Kong R, Duan H, Sheng Z, Xu K, Acharya P, Chen X, Cheng C, Dingens AS, Gorman J, Sastry M, Shen CH, Zhang B, Zhou T, Chuang GY, Chao CW, Gu Y, Jafari AJ, Louder MK, O'Dell S, Rowshan AP, Viox EG, Wang Y, Choi CW, Corcoran MM, Corrigan AR, Dandey VP, Eng ET, Geng H, Foulds KE, Guo Y, Kwon YD, Lin B, Liu K, Mason RD, Nason MC, Ohr TY, Ou L, Rawi R, Sarfo EK, Schön A, Todd JP, Wang S, Wei H, Wu W; NISC Comparative Sequencing Program; Mullikin JC, Bailer RT, Doria-Rose NA, Karlsson Hedestam GB, Scorpio DG, Overbaugh J, Bloom JD, Carragher B, Potter CS, Shapiro L, Kwong PD, Mascola JR. Antibody Lineages with Vaccine-Induced Antigen-Binding Hotspots Develop Broad HIV Neutralization. Cell. 2019 Jul 25;178(3):567-584.e19. doi: 10.1016/j.cell.2019.06.030.PMID: 31348886
Kwong PD, Chuang GY, DeKosky BJ, Gindin T, Georgiev IS, Lemmin T, Schramm CA, Sheng Z, Soto C, Yang AS, Mascola JR, Shapiro L. Antibodyomics: bioinformatics technologies for understanding B-cell immunity to HIV-1. Immunol Rev. 2017 Jan;275(1):108-128. doi: 10.1111/imr.12480. PMID: 28133812
Kwong PD, Wyatt R, Robinson J, Sweet RW, Sodroski J, Hendrickson WA. Structure of an HIV gp120 envelope glycoprotein in complex with the CD4 receptor and a neutralizing human antibody. Nature. 1998 Jun 18;393(6686):648-59. doi: 10.1038/31405.PMID: 9641677
Li H, Wang S, Kong R, Ding W, Lee FH, Parker Z, Kim E, Learn GH, Hahn P, Policicchio B, Brocca-Cofano E, Deleage C, Hao X, Chuang GY, Gorman J, Gardner M, Lewis MG, Hatziioannou T, Santra S, Apetrei C, Pandrea I, Alam SM, Liao HX, Shen X, Tomaras GD, Farzan M, Chertova E, Keele BF, Estes JD, Lifson JD, Doms RW, Montefiori DC, Haynes BF, Sodroski JG, Kwong PD, Hahn BH, Shaw GM. Envelope residue 375 substitutions in simian-human immunodeficiency viruses enhance CD4 binding and replication in rhesus macaques. Proc Natl Acad Sci U S A. 2016 Jun 14;113(24):E3413-22. doi: 10.1073/pnas.1606636113. Epub 2016 May 31.
McLellan JS, Chen M, Joyce MG, Sastry M, Stewart-Jones GB, Yang Y, Zhang B, Chen L, Srivatsan S, Zheng A, Zhou T, Graepel KW, Kumar A, Moin S, Boyington JC, Chuang GY, Soto C, Baxa U, Bakker AQ, Spits H, Beaumont T, Zheng Z, Xia N, Ko SY, Todd JP, Rao S, Graham BS, Kwong PD. Structure-based design of a fusion glycoprotein vaccine for respiratory syncytial virus. Science. 2013 Nov 1;342(6158):592-8. doi: 10.1126/science.1243283.PMID: 24179220
Roark RS, Li H, Williams WB, Chug H, Mason RD, Gorman J, Wang S, Lee FH, Rando J, Bonsignori M, Hwang KK, Saunders KO, Wiehe K, Moody MA, Hraber PT, Wagh K, Giorgi EE, Russell RM, Bibollet-Ruche F, Liu W, Connell J, Smith AG, DeVoto J, Murphy AI, Smith J, Ding W, Zhao C, Chohan N, Okumura M, Rosario C, Ding Y, Lindemuth E, Bauer AM, Bar KJ, Ambrozak D, Chao CW, Chuang GY, Geng H, Lin BC, Louder MK, Nguyen R, Zhang B, Lewis MG, Raymond DD, Doria-Rose NA, Schramm CA, Douek DC, Roederer M, Kepler TB, Kelsoe G, Mascola JR, Kwong PD, Korber BT, Harrison SC, Haynes BF, Hahn BH, Shaw GM. Recapitulation of HIV-1 Env-antibody coevolution in macaques leading to neutralization breadth. Science. 2021 Jan 8;371(6525):eabd2638. doi: 10.1126/science.abd2638. Epub 2020 Nov 19. PMID: 33214287
Shapiro L, Fannon AM, Kwong PD, Thompson A, Lehmann MS, Grübel G, Legrand JF, Als-Nielsen J, Colman DR, Hendrickson WA. Structural basis of cell-cell adhesion by cadherins. Nature. 1995 Mar 23;374(6520):327-37. doi: 10.1038/374327a0.PMID: 7885471
Wang H, Cheng C, Dal Santo JL, Hsiang Shen CH, Bylund T, Henry AR, Howe CA, Hwang J, Morano HC, Morris DJ, Pletnev S, Roark RS, Zhou T, Hansen BT, Hoyt FH, Johnston TS, Wang S, Zhang B, Ambrozak DR, Becker JE, Kwong PD. Potent and broad HIV-1 neutralization in fusion peptide-primed SHIV-infected macaques. Cell 2024; Epub adhead of print, 28 October 2024. https://doi.org/10.1016/j.cell.2024.10.003(link is external and opens in a new window)