Figure 2. Animal models for immunogen evaluation and analysis of antibody responses.
(a) Five animal models (non-human primates, cows, guinea pigs, rabbits and mice) have been used to evaluate the immunogenicity of several current vaccine candidates. Within the mouse model, wild-type, immunoglobulin (Ig) gene knock-in mice (containing the rearranged Ig genes for the inferred unmutated common ancestor (UCA) versions of HIV broadly neutralizing antibodies), and mice transgenic for the human Ig locus have been used. The particular immunogen design platforms tested within each animal model system are shown. (b) Schematic depicting three critical technologies that have been used to evaluate vaccine-elicited antibody responses. Monoclonal antibodies, isolated by antigen-specific single B cell sorting and deep sequencing of B cell transcripts can then be used to identify many members of the corresponding B cell lineages. Finally, electron microscopy can be used to identify the epitopes of the vaccine-elicited antibodies. Information derived from the technologies can be fed back to support iterative immunogen design.