Functional, Immunogenetic, and Structural Convergence in Influenza Immunity between Humans and Macaques

Area of Science:

• Immunology
• Vaccinology
• Virology

Background:

• Human B cell immunity to the influenza hemagglutinin (HA) stem region, a universal influenza vaccine target, is often restricted.
• Studying this immunity outside humans presents challenges due to its stereotyped nature.

Purpose of the Study:

• To investigate if macaques vaccinated with HA stem immunogens can elicit human-like B cell responses.
• To compare macaque-derived antibodies to human broadly neutralizing antibodies (bnAbs) targeting conserved HA epitopes.

Main Methods:

• Vaccination of macaques with a HA stem immunogen.
• Analysis of B cell lineages and antibody sequences elicited in response to vaccination.
• Functional and structural characterization of macaque-derived antibodies.

Main Results:

• Macaques generated human-like public B cell lineages targeting conserved central stem and anchor epitopes of the HA stem.
• Central stem antibodies in macaques were derived from V_H1-138, analogous to human V_H1-69.
• Anchor bnAbs in macaques exhibited the human-like NWP motif, with both bnAb types being functionally and structurally similar to human counterparts.

Conclusions:

• The macaque immunoglobulin repertoire supports the development of human-like public broadly neutralizing antibody responses to influenza HA.
• Macaques serve as a valuable model for studying universal influenza vaccine responses.
• Homologous germline-encoded immunity and conserved immune repertoire shaping in macaques and humans are suggested.