Monoclonal Antibody Discovery in HIV and Malaria
Optimizing antibody isolation, characterization, and production with a rapid, cost-efficient platform
The Sather lab studies the interactions between pathogens and the host immune system with the goal of leveraging research discoveries to develop novel vaccines and vaccination regimens. Currently, they focus on three major pathogens: HIV-1, the causative agent of AIDS, and Plasmodium falciparum and Plasmodium vivax, the two major causative agents of malaria.
To create research tools and advance clinical innovations for infectious diseases, Dr. Sather and colleagues developed a platform for generating, screening, and producing monoclonal antibodies (mAbs). Their method is faster, more cost-efficient, and flexible than many existing technologies. The method isolates B cells from immunized mice and selects single, antigen-positive cells by fluorescence-activated cell sorting (FACs) for culturing and screening. This step eliminates the need to generate hybridomas. From the best B-cell candidates, B-cell receptor sequences are retrieved by 5’ RACE and cloned in a single step into antibody-expression vectors. The vectors are introduced into mammalian culture cells to produce recombinant mAbs for further analysis and validation. This method generates a diverse array of mAbs with a range of specificities, binding affinities, and epitope-binding sites. Dr. Sather and collaborators have used their mAb discovery platform to generate mAbs against a variety of Plasmodium target proteins.
Dr. Sather is interested in expanding applications of the mAb platform in vaccine and therapeutic discovery. Examples of potential partnership projects include: 1) developing innovative techniques and tools for designing, isolating, and harvesting mAbs; 2) immunizing with complex antigens instead of simple peptides to produce mAbs that recognize physiological, three-dimensional targets; and 3) using humanized mouse models to produce mAbs for modeling effective vaccines and developing passive prophylatics and treatments for infectious diseases.
Stage of Development
- Preclinical in vitro
- Preclinical in vivo
- Collaborative research opportunity
- Sponsored research agreement
- Licensing agreement (PCT/US2016/015831)
- Consultation agreement
Immune repertoire sequencing
- Schafer C, Dambrauskas N, Steel RW, Carbonetti S....Sather DN. A recombinant antibody against Plasmodium vivax UIS4 for distinguishing replicating from dormant liver stages. Malar J. 2018;17(1):370.
- Steel RWJ, Pei Y, Camargo N, Kaushansky A, Dankwa DA....Sather DN, Kappe SHI. Plasmodium yoelii S4/CelTOS is important for sporozoite gliding motility and cell traversal. Cell Microbiol. 2018;20(4): e12817.
- Carbonetti S, Oliver BG, Vigdorovich V, Dambrauskas N, Sack B, Bergl E, Kappe SHI, Sather DN. A method for the isolation and characterization of functional murine monoclonal antibodies by single B cell cloning. J Immunol Methods. 2017;448:66-73.