Assistant Professor / The Scripps Research Institute
The Scripps Research Institute, Department of Immunology and Microbiology 10550 North Torrey Pines Road, IMM-2 La Jolla, CA 92037
Dr. Briney’s work resulted in several publications, including studies published in Nature, Science and Cell, as well as co-authorship on studies published in Science, Immunity, Science Translational Medicine, Cell Reports, PNAS and PLoS Pathogens.
Together with his team, Dr. Briney explores a variety of scientific fields and has made a number of significant contributions. He used cutting-edge, next-generation sequencing (NGS) technology to genetically characterize the circulating and tissue-resident human antibody repertoire, and this work now serves as a foundation for a generalizable understanding of humoral responses to immunization and infection. He is also responsible for discovering significant genetic differences between antibody repertoires isolated from lymphoid and mucosal tissues, revealing the profound effect of antigen exposure on the composition of localized, tissue-resident antibody repertoires.
In addition to that, Bryan Briney identified the origin of unique genetic features found in broadly neutralizing HIV-1 antibodies — as broadly neutralizing antibodies to HIV-1 typically contain unusual genetic features, including extensive somatic mutation, extraordinarily long HCDR3 regions, and somatic hypermutation (SHM)-induced insertions and/or deletions (indels), Dr. Briney analyzed the circulating antibody repertoires of several healthy donors to compute the frequency and genetic origin of such features.
Another one of Dr. Briney’s scientific focuses revolves around the development and evaluation of rationally designed germline-targeting HIV immunogens. Elicitation of a broadly neutralizing antibody (bnAb) response is thought to be a highly desirable feature of an effective HIV vaccine, but induction of such antibodies by immunization has proven extremely difficult. A promising vaccine strategy involves rationally designed immunogens that have been engineered to specifically target the germline precursors of known bnAbs and guide the development of these precursors toward mature bnAb function. As a result of several productive collaborations, Dr. Briney and his team developed a series of immunogens that effectively target the germline precursors of the VRC01 class of HIV bnAbs and efficiently direct the genetic and functional development of these antibodies.
Additionally, Bryan Briney worked on genetic development and maturation of broadly neutralizing anti-viral antibodies. Exceptionally broad and potently neutralizing antibodies have been characterized for both HIV-1 and influenza, but a vaccine that can elicit such antibodies has not yet been identified. Dr. Briney leveraged next-generation sequencing to rapidly and comprehensively study the progression of bnAb lineages, and in the case of HIV, he defined the effects of maturation on neutralization and binding in the PGT121 lineage of broadly neutralizing antibodies. Together with his team, Dr. Briney found similar but complementary functionality between the lineage members, emphasizing the importance of parallel clonal maturation and identified specific epitopes that were strongly associated with either cross-reactive or mono-specific antibodies, which may serve as templates for design of a vaccine that minimizes antibody mediated enhancement.