Population-level genomic analysis of immunoglobulin loci variation in rhesus macaques reveals extensive germline diversity

Ayelet Peres; Amit A Upadhyay; Vered Klein; Swati Saha; Oscar L Rodriguez; Zachary M Vanwinkle; Kirti Karunakaran; Amanda Metz; William Lauer; Mark C Lin; Timothy Melton; Lukas Granholm; Pazit Polak; Samuel M Peterson; Eric J Peterson; Nagarajan Raju; Kaitlyn Shields; Steven Schultze; Thang Ton; Adam J Ericsen; Stacey A Lapp; Francois Villinger; Mats Ohlin; Christopher A Cottrell; Rama R Amara; Cynthia A Derdeyn; Shane Crotty; William R Schief; Gunilla B Karlsson Hedestam; Melissa L Smith; William Lees; Corey T Watson; Gur Yaari; Steven E Bosinger

doi:10.1016/j.immuni.2025.12.002

Population-level genomic analysis of immunoglobulin loci variation in rhesus macaques reveals extensive germline diversity

Immunity. 2026 Jan 13;59(1):213-228.e6. doi: 10.1016/j.immuni.2025.12.002. Epub 2026 Jan 5.

Authors

Ayelet Peres¹, Amit A Upadhyay², Vered Klein³, Swati Saha⁴, Oscar L Rodriguez⁴, Zachary M Vanwinkle⁵, Kirti Karunakaran⁵, Amanda Metz⁵, William Lauer⁴, Mark C Lin⁵, Timothy Melton⁵, Lukas Granholm⁵, Pazit Polak⁶, Samuel M Peterson⁷, Eric J Peterson⁸, Nagarajan Raju⁵, Kaitlyn Shields⁴, Steven Schultze⁴, Thang Ton⁵, Adam J Ericsen⁵, Stacey A Lapp⁵, Francois Villinger⁹, Mats Ohlin¹⁰, Christopher A Cottrell¹¹, Rama R Amara¹², Cynthia A Derdeyn¹³, Shane Crotty¹⁴, William R Schief¹⁵, Gunilla B Karlsson Hedestam¹⁶, Melissa L Smith⁴, William Lees¹⁷, Corey T Watson¹⁸, Gur Yaari¹⁹, Steven E Bosinger²⁰

Affiliations

¹ Department of Pathology, Yale School of Medicine, New Haven, CT 06250, USA; Faculty of Engineering, Bar Ilan University, Ramat Gan, Israel; Bar Ilan institute of Nanotechnology and Advanced Materials, Bar Ilan University, Ramat Gan, Israel.
² Emory National Primate Research Center, Atlanta, GA 30329, USA; Department of Pathology & Laboratory Medicine, Emory University School of Medicine, Atlanta, GA 30322, USA.
³ Faculty of Engineering, Bar Ilan University, Ramat Gan, Israel; Bar Ilan institute of Nanotechnology and Advanced Materials, Bar Ilan University, Ramat Gan, Israel.
⁴ Department of Biochemistry and Molecular Genetics, University of Louisville, Louisville, KY 40292, USA.
⁵ Emory National Primate Research Center, Atlanta, GA 30329, USA.
⁶ Faculty of Engineering, Bar Ilan University, Ramat Gan, Israel.
⁷ Division of Genetics, Oregon National Primate Research Center, Beaverton, OR 97006, USA.
⁸ Wisconsin National Primate Research Center, Madison, WI 53175, USA.
⁹ New Iberia Research Center, University of Louisiana at Lafayette, Lafayette, LA 70562, USA.
¹⁰ Department of Immunotechnology, Lund University, Lund, Sweden; SciLifeLab, Lund University, Lund, Sweden.
¹¹ Department of Immunology and Microbial Science, The Scripps Research Institute, La Jolla, CA 92037, USA; Consortium for HIV/AIDS Vaccine Development (CHAVD), The Scripps Research Institute, La Jolla, CA 92037, USA.
¹² Emory National Primate Research Center, Atlanta, GA 30329, USA; Department of Microbiology and Immunology, Emory School of Medicine, Emory University, Atlanta, GA 30322, USA.
¹³ Department of Laboratory Medicine and Pathology, University of Washington, Seattle, WA 98195, USA; Infectious Diseases and Translational Medicine Unit, Washington National Primate Research Center, University of Washington, Seattle, WA 98195, USA.
¹⁴ Consortium for HIV/AIDS Vaccine Development (CHAVD), The Scripps Research Institute, La Jolla, CA 92037, USA; Center for Vaccine Innovation, La Jolla Institute for Immunology, La Jolla, CA 92037, USA; Department of Medicine, Division of Infectious Diseases and Global Public Health, University of California, San Diego (UCSD), La Jolla, CA 92037, USA.
¹⁵ Department of Immunology and Microbial Science, The Scripps Research Institute, La Jolla, CA 92037, USA; Consortium for HIV/AIDS Vaccine Development (CHAVD), The Scripps Research Institute, La Jolla, CA 92037, USA; IAVI Neutralizing Antibody Center, The Scripps Research Institute, La Jolla, CA 92037, USA; Moderna, Inc., Cambridge, MA 02142, USA.
¹⁶ Department of Microbiology, Tumor and Cell Biology, Karolinska Institutet, Stockholm, Sweden.
¹⁷ Faculty of Engineering, Bar Ilan University, Ramat Gan, Israel; Department of Biochemistry and Molecular Genetics, University of Louisville, Louisville, KY 40292, USA.
¹⁸ Department of Biochemistry and Molecular Genetics, University of Louisville, Louisville, KY 40292, USA. Electronic address: corey.watson@louisville.edu.
¹⁹ Department of Pathology, Yale School of Medicine, New Haven, CT 06250, USA; Faculty of Engineering, Bar Ilan University, Ramat Gan, Israel; Bar Ilan institute of Nanotechnology and Advanced Materials, Bar Ilan University, Ramat Gan, Israel. Electronic address: gur.yaari@yale.edu.
²⁰ Emory National Primate Research Center, Atlanta, GA 30329, USA; Department of Pathology & Laboratory Medicine, Emory University School of Medicine, Atlanta, GA 30322, USA. Electronic address: steven.bosinger@emory.edu.

PMID: 41494536
DOI: 10.1016/j.immuni.2025.12.002

Abstract

Rhesus macaques (RMs) are a vital model for studying human disease and are invaluable to preclinical vaccine research, particularly for the study of broadly neutralizing antibody responses. Such studies require robust genetic resources for antibody-encoding genes within the immunoglobulin (IG) loci. The complexity of the IG loci has historically made them challenging to characterize accurately. To address this, we developed experimental and computational methodologies to generate a collection of integrated antibody repertoire and long-read genomic sequencing data in 106 Indian-origin RMs. We created a resource of IG heavy- and light-chain variable (V), diversity (D), and joining (J) alleles, as well as leader, intronic, and recombination signal sequences (RSSs). This includes the curation of 1,095 previously unidentified alleles, unveiling tremendous diversity and expanding existing IG allele sets by 40%. This publicly available, continually updated resource (https://vdjbase.org/reference_book/Rhesus_Macaque) provides the foundation for advancing RM immunogenomics, vaccine discovery, and translational research.

Keywords: B cell receptor; HIV; antibodies; broadly neutralizing antibodies; database; genomics; germline inference; immunoglobulins; repertoire; rhesus macaque.

MeSH terms

Alleles
Animals
Genetic Variation*
Genomics / methods
Humans
Immunoglobulin Variable Region / genetics
Macaca mulatta* / genetics
Macaca mulatta* / immunology

Substances

Immunoglobulin Variable Region

Grants and funding

P51 OD011106/OD/NIH HHS/United States