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Updated: Jan 18, 2026
06:25
Analysis of Simian Immunodeficiency Virus-specific CD8+ T-cells in Rhesus Macaques by Peptide-MHC-I Tetramer Staining
Published on: December 23, 2016
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Functional, immunogenetic, and structural convergence in influenza immunity between humans and macaques
Maya Sangesland1, Ning Li2, Yaroslav Tsybovsky2
1Vaccine Research Center (VRC), National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA.
Science Translational Medicine
|September 10, 2025
Summary
Cynomolgus macaques vaccinated with an influenza hemagglutinin (HA) stem immunogen produced humanlike broadly neutralizing antibodies (bnAbs). These antibodies target conserved HA stem regions, validating the macaque model for universal influenza vaccine development.
Area of Science:
- Immunology
- Vaccinology
- Virology
Background:
- Human B cell immunity to influenza hemagglutinin (HA) stem is restricted, hindering research.
- The HA stem is a universal target for influenza vaccines.
- Studying HA stem immunity outside humans presents challenges.
Purpose of the Study:
- To investigate if cynomolgus macaques can elicit humanlike B cell responses to HA stem immunogens.
- To evaluate the macaque model for translational vaccinology of influenza.
- To understand the immunogenetic basis of broadly neutralizing antibody (bnAb) production against influenza HA.
Main Methods:
- Vaccination of cynomolgus macaques with an HA stem immunogen.
- Analysis of B cell lineage responses, focusing on antibody V gene usage and epitope targeting.
- Functional and structural characterization of elicited antibodies.
- Comparison of macaque-derived bnAbs with human counterparts.
Main Results:
- Macaques generated humanlike public B cell lineages targeting conserved HA stem and anchor epitopes.
- Central stem bnAbs in macaques were derived from VH1-138, analogous to human VH1-69.
- Anchor bnAbs in macaques contained the canonical NWP motif, similar to human bnAbs.
- Elicited bnAb lineages were functionally and structurally analogous to human bnAbs, mediated by germline-encoded motifs.
Conclusions:
- The macaque immunoglobulin repertoire supports humanlike public bnAb responses to influenza HA.
- The macaque model is valuable for translational vaccinology of universal influenza vaccines.
- Homologous germline-encoded immunity plays a significant role, suggesting conserved immune repertoire evolution in macaques and humans.
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