Requirement for sequential immunization. (A) Panel illustrates the finding that HIV-1 antibodies are highly somatically mutated. (B) Panel shows that germline-reverted antibodies fail to bind to most HIV-1 antigens. (C) Panel illustrates the observation that HIV-1 and bNAbs develop in sequence over time. (D) Panel shows the results of knock-in mouse immunization experiments that showed that multiple immunogens would be required for bNAb development.
Linking sequential immunization to somatic mutation and bNAb development. The figure illustrates the immunization scheme that led to bNAb development in mice that carry the PGT121 germline gene. The initial immunogen had the highest affinity for the germline-reverted antibody, and subsequent immunogens had decreasing affinities. Somatic mutation increased with immunization.