Antigenic sites in influenza H1 hemagglutinin display species-specific immunodominance
Sean T. H. Liu, … , Florian Krammer, Peter Palese
Sean T. H. Liu, … , Florian Krammer, Peter Palese
Published November 1, 2018; First published September 6, 2018
Citation Information: J Clin Invest. 2018;128(11):4992-4996. https://doi.org/10.1172/JCI122895.
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Concise Communication Immunology Virology

Antigenic sites in influenza H1 hemagglutinin display species-specific immunodominance

Abstract

Hemagglutination inhibition (HI) titers are a major correlate of protection for influenza-related illness. The influenza virus hemagglutinin possesses antigenic sites that are the targets of HI active antibodies. Here, a panel of mutant viruses each lacking a classically defined antigenic site was created to compare the species-specific immunodominance of the antigenic sites in a clinically relevant hemagglutinin. HI active antibodies of antisera from influenza virus–infected mice targeted sites Sb and Ca2. HI active antibodies of guinea pigs were not directed against any specific antigenic site, although trends were observed toward Sb, Ca2, and Sa. HI titers of antisera from infected ferrets were significantly affected by site Sa. HI active antibodies of adult humans followed yet another immunodominance pattern, in which sites Sb and Sa were immunodominant. When comparing the HI profiles among different species by antigenic cartography, animals and humans grouped separately. This study provides characterizations of the antibody-mediated immune responses against the head domain of a recent H1 hemagglutinin in animals and humans.

Authors

Sean T. H. Liu, Mohammad Amin Behzadi, Weina Sun, Alec W. Freyn, Wen-Chun Liu, Felix Broecker, Randy A. Albrecht, Nicole M. Bouvier, Viviana Simon, Raffael Nachbagauer, Florian Krammer, Peter Palese

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Figure 1

Head domain epitopes of pandemic-like H1 HA and amino acid sequences of mutant epitope substitutions.

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Head domain epitopes of pandemic-like H1 HA and amino acid sequences of ...
(A) Crystal structure of pandemic H1 HA trimer (PDB:3UBE) (10) (top view and side view, 1 monomer in white and 2 monomers in gray) with classically defined antigenic sites colored as follows: Sa in red, Sb in green, Ca1 in blue, Ca2 in magenta, and Cb in orange. Modeling performed with PyMOL (The PyMOL Molecular Graphics System, Version 2.0.1, Schrödinger, LLC). A sialic acid molecule (yellow) is present in the receptor binding pocket of the white HA monomer. (B) Amino acid sequences of the antigenic sites of pandemic-like H1 strain A/Michigan/45/2015 are highlighted as follows: Sa in red, Sb in green, Ca1 in blue, Ca2 in magenta, and Cb in orange. Amino acid sequences of heterologous epitopes for the mutant virus panel are listed below the respective pandemic H1 sites. Amino acids in black represent substituted residues. Amino acids in gray are unchanged.