Antigenic sites in influenza H1 hemagglutinin display species-specific immunodominance
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
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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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 2

HI profiles of antisera from mice, guinea pigs, and ferrets.

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HI profiles of antisera from mice, guinea pigs, and ferrets. Hemagglutin...
Hemagglutination inhibition titers of mouse (n = 10) (A), guinea pig (n = 4) (B), and ferret (n = 5) (C) antisera were measured against a panel of mutant viruses (see Figure 1B). Naive animals were intranasally infected with 1 × 105 PFU of a pandemic-like H1N1 virus, A/Michigan/45/2015, and antisera were harvested at 4 weeks after infection (except for 2 ferret antisera, which were harvested at 3 weeks after infection). The HI profiles for each species are listed; statistically significant reductions are in red and minimal reductions are in gray. Experiments were performed in technical duplicates. Circles represent averaged HI titers of an individual animal’s serum. Bars represent the geometric mean ± geometric SD. Statistical significance was determined between the mutant virus to the WT H1 virus using Dunn’s corrected Kruskal-Wallis 1-way ANOVA of the mean HI titers (*P ≤ 0.05, ***P ≤ 0.001, ****P ≤ 0.0001).