B-Cell Repertoire Sequencing For HIV and Other Infectious Diseases

Sequencing complete B-cell receptor genes to characterize effective immune responses

Technology Overview

Dr. Noah Sather

The Sather lab has developed a next-generation sequencing pipeline based on Illumina architecture to evaluate B-cell receptor repertoires from model organisms and humans. This platform obtains full variable region sequences of recombined B-cell receptor genes for the heavy and light chain loci, allowing for the full analysis of B cell evolution, clonal structure, and diversity. The Sather lab is also developing protocols for single-cell sequencing of B-cell repertoires with matched heavy and light chains and for assessing matched constant region IgG subclass repertoires.

The Sather group is using the platform to analyze immune responses to HIV with the goal of guiding development of effective anti-HIV vaccines and vaccine regimens. HIV is known for rapidly mutating and evolving to elude the immune system. Therefore, an effective HIV vaccine will need to induce broadly neutralizing antibodies (bNAbs) that protect against an array of changing viruses. About 10-30% of people infected by HIV-1 stably develop these bNAbs against the HIV envelope glycoprotein (Env).

Dr. Sather’s team is using a technology-driven approach to investigate how anti-HIV bNAbs develop in natural infections of humans and after immunization of model organisms with Env. In addition to characterizing the Env domains that elicit neutralizing vs. non-neutralizing anti-HIV antibodies, they are analyzing B-cell repertoires to determine how Env exposure drives B-cell evolution. The goal is determining how some B-cell lineages expand and evolve to result in an effective neutralizing response.

The methods Dr. Sather is developing and the evidence his group is obtaining about the B-cell response to immunogens are especially useful for vaccine development. Even if a candidate vaccine does not achieve clinically relevant benchmarks, the approach provides specific data on how to make iterative improvements. Dr. Sather is interested in using his expertise in host-pathogen interactions, development of protective immunity, and B-cell analysis to develop a range of vaccines and treatments for infectious diseases.

Stage of Development

• Preclinical in vitro
• Preclinical in vivo

Partnering Opportunities

• Collaborative research opportunity
• Sponsored research agreement
• Consultation agreement

• Immune repertoire sequencing

Publications

1. Yacoob C, Lange MD, Cohen K, Lathia K, Feng J, Glenn J...Sather DN, L Stamatatos. B cell clonal lineage alterations upon recombinant HIV-1 envelope immunization of rhesus macaques. PLoS Pathog. 2018;14(6):e1007120.
2. Vigdorovich V, Oliver BG, Carbonetti S, Dambrauskas N, Lange MD....Sather DN. Repertoire comparison of the B-cell receptor-encoding loci in humans and rhesus macaques by next-generation sequencing. Clin Transl Immunology. 2016;5:e93.
3. Hessell AJ, Malherbe DC, Pissani F, McBurney S, Krebs SJ.... Sather DN, Haigwood NL. Achieving potent autologous neutralizing antibody responses against tier 2 HIV-1 viruses by strategic selection of envelope immunogens. J Immunol. 2016;196(7):3064-3078.
4. Carbonetti S, Oliver BG, Glenn J, Stamatatos L, Sather DN. Soluble HIV-1 envelope immunogens derived from an elite neutralizer elicit cross-reactive V1V2 antibodies and low potency neutralizing antibodies. PLoS One. 2014;9:e86905.

Learn More

• Noah Sather, PhD
• Sather Lab