Evaluating southern pigtail macaques as an immunological model for human antibody responses

Abstract Antibody specificity is primarily derived from immunoglobulin (Ig) genes, which exhibit extensive genetic polymorphism both within and across species. Non-human primates (NHP) such as pigtail macaques are often used as preclinical models for immunological studies because of their genetic proximity to humans, despite a comparatively poor characterisation of their immunoglobulin loci and its impact on antibody specificity. To determine how pigtail macaque antibody responses differ from humans, we annotated the immunoglobulin loci of two pigtail macaques and compared BCR sequences and antigen binding sites of SARS-CoV-2 spike-specific antibodies derived from pigtail macaque or human B cells. Pigtail macaques showed high levels of genetic diversity across all three immunoglobulin loci. Spike-specific BCRs from a single pigtail macaque contained greater number of heavy chain variable genes compared to sequences obtained from six humans. Nevertheless, macaque antibodies targeted similar receptor binding domain (RBD) epitopes as humans. This work highlights the need for further understanding of the impacts of immunogenetics especially in light of recent advances in germline-based vaccine strategies.