B cell receptor analysis using single cell sequencing reveals preferential antibody expression in a HIV candidate vaccine study

HIV (human immunodeficiency virus) is a virus that infects different cell types in the immune system. While different monoclonal antibodies have been identified, because of the antigenic diversity of HIV, defining broad neutralising antibodies (bnAbs) it has been very challenging. Using the 10x Chromium technology partitioning system, we performed single-cell sequencing of the B cell repertoire and analysed a cohort of 48 HIV-negative subjects randomised into 4 groups each receiving a different HIV vaccine regime to investigate the type of antibody response to each of the proteins in the vaccine groups, namely ConM SOSIP, EDC ConM SOSIP, ConS UFO and EDC ConS UFO. We recovered over >300,000 single cells and reconstructed full-length antibody heavy- and light-chain variable regions from individual memory B cells, plasmablasts, naive B cells and activated B cells as well as retrieved their transcriptome profile to correctly separate the different populations within each individual. We identified seven clonotypes representing functional antibodies against vaccine candidate proteins. We reconstructed their phylogenetic tree and confirmed they were novel antibodies in response to HIV. These were mainly antibodies in response to two of the four protein candidates, namely ConS UFO and EDC ConS UFO.