Fig. 2. B-cell lineage-based approach to vaccine design.

Mature BNAbs can be isolated from HIV-1 infected donors using modern methods such as memory B-cell culture or sorting of antigen-specific B-cells. Based on the known BNAb sequence, next generation sequencing can be used to find numerous clonal relatives of the mature BNAb. If appropriate longitudinal samples are available, it is possible to infer the full antibody lineage, including the UA and IA. The expressed UA and IA sequences can then be used as templates for the design of HIV-1 immunogens with high affinity binding. Since the antibody lineage is known to evolve in response to viral evolution, it may be possible to design sequential immunogens with high affinity binding for the UA and IA, thus guiding the antibody response toward the mature antibody with broad neutralizing activity.