Functional, immunogenetic, and structural convergence in influenza immunity between humans and macaques

A major challenge with antibody immunogenetics is that preclinical animal models do not share the same immunoglobulin repertoire. Attempts have been made to insert the human immunoglobulin repertoire into mice, but other major differences between humans and mice limit the translational utility of these models. Here, Sangesland et al. asked whether cynomolgus macaques, which are more genetically similar to humans but have a distinct immunoglobulin locus, can recapitulate responses to the influenza virus as observed in humans. They found that the cynomolgus macaque response to a hemagglutinin (HA) stem was remarkably similar to that of humans vaccinated with the same immunogen, targeting the same central stem and anchor epitopes of the HA with a preference for germline-encoded motifs. These data not only support the macaque model as essential for translational vaccinology but also suggest shared evolution of the immunoglobulin repertoire between humans and macaques.