Human monoclonal antibodies are emerging as powerful tools in combating infectious disease, both as direct prophylactics and as reagents to identify vulnerable sites on pathogens to guide vaccine design. At the Antibody Biology Unit (ABU), we aim to use cutting-edge technology to study B cells at the single cell level and to identify and characterize human monoclonal antibodies against a range of pathogens. We have two major aims:
- To study basic antibody biology. The sequences of monoclonal antibodies isolated from a vaccinated or naturally infected individual provide a high-resolution portrait of the antibody response to a given pathogen. Information revealed includes the predominant antibody isotype that is generated, the degree of somatic mutation and affinity maturation required for the development of a potent neutralizing response, and the preferential usage of specific VH genes to mount a response against a given antigen.
- To investigate the use of monoclonal antibodies for prevention of infection and as tools for vaccine design. Monoclonal antibodies that are isolated will be screened in in vitro and in vivo assays to determine their potency in preventing infection. Their affinity for their targets will be measured using biophysical assays. In collaboration with structural biologists, we will identify the specific epitopes targeted by the most potent antibodies and develop these sites as novel vaccine candidates. The most potent antibodies will also be considered as candidates to prevent infection in early-phase clinical trials.
The primary focus of the unit will be on malaria. Plasmodium falciparum causes approximately 400,000 deaths a year and remains a serious global health threat. Antibodies have been shown to be key mediators of protection against different stages of the P. falciparum life cycle, but the antibody response to malaria has only recently been studied at high resolution. The biology of the antibody response to P. falciparum is complex and fascinating. Recently, we identified broadly reactive antibodies from individuals living in malaria-endemic areas that contain a LAIR1 insert (an extra immunoglobulin-like domain) that is originally encoded in a different chromosome. This insert confers broad reactivity and is somatically mutated along with the rest of the antibody. This insertion event appears to be quite common in individuals living in different malaria-endemic regions (5-10% of individuals). In a separate study, we identified potent human monoclonal antibodies targeting a novel epitope on the P. falciparum circumsporozoite protein, the major sporozoite coat protein. This site is now being investigated as a new vaccine candidate.
Our platform is adaptable to any target. This unit will also study human monoclonal antibodies against other infectious agents, including the novel coronavirus SARS-CoV-2, as well as non-infectious targets.
Dr. Tan received his Ph.D. in 2016 from the University of Oxford, England. His Ph.D. work focused on the identification of unusual LAIR1-containing human monoclonal antibodies targeting antigens on Plasmodium falciparum-infected erythrocytes. After his Ph.D., he was awarded a Sir Henry Wellcome Postdoctoral Fellowship to continue his work on human monoclonal antibodies against P. falciparum in 2017. He joined the Laboratory of Immunogenetics as a tenure-track investigator in 2020.
- Dacon C, Tucker C, Peng L, Lee CD, Lin TH, Yuan M, Cong Y, Wang L, Purser L, Williams JK, Pyo CW, Kosik I, Hu Z, Zhao M, Mohan D, Cooper AJR, Peterson M, Skinner J, Dixit S, Kollins E, Huzella L, Perry D, Byrum R, Lembirik S, Drawbaugh D, Eaton B, Zhang Y, Yang ES, Chen M, Leung K, Weinberg RS, Pegu A, Geraghty DE, Davidson E, Douagi I, Moir S, Yewdell JW, Schmaljohn C, Crompton PD, Holbrook MR, Nemazee D, Mascola JR, Wilson IA, Tan J. Broadly neutralizing antibodies target the coronavirus fusion peptide. Science. 2022:eabq3773.
- Cho H, Gonzales-Wartz KK, Huang D, Yuan M, Peterson M, Liang J, Beutler N, Torres JL, Cong Y, Postnikova E, Bangaru S, Talana CA, Shi W, Yang ES, Zhang Y, Leung K, Wang L, Peng L, Skinner J, Li S, Wu NC, Liu H, Dacon C, Moyer T, Cohen M, Zhao M, Lee FE, Weinberg RS, Douagi I, Gross R, Schmaljohn C, Pegu A, Mascola JR, Holbrook M, Nemazee D, Rogers TF, Ward AB, Wilson IA, Crompton PD, Tan J. Bispecific antibodies targeting distinct regions of the spike protein potently neutralize SARS-CoV-2 variants of concern. Sci Transl Med. 2021;13(616):eabj5413.
- Tan J, Cho H, Pholcharee T, Pereira LS, Doumbo S, Doumtabe D, Flynn BJ, Schön A, Kanatani S, Aylor SO, Oyen D, Vistein R, Wang L, Dillon M, Skinner J, Peterson M, Li S, Idris AH, Molina-Cruz A, Zhao M, Olano LR, Lee PJ, Roth A, Sinnis P, Barillas-Mury C, Kayentao K, Ongoiba A, Francica JR, Traore B, Wilson IA, Seder RA, Crompton PD. Functional human IgA targets a conserved site on malaria sporozoites. Sci Transl Med. 2021;13(599).
Related Scientific Focus Areas
Microbiology and Infectious Diseases
This page was last updated on Sunday, July 31, 2022