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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 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

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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 3

HI profiles for adult humans before and after 2017–2018 seasonal vaccination.

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HI profiles for adult humans before and after 2017–2018 seasonal vaccina...
(A) HI activities of plasma samples (n = 36) collected from 18 adult donors before and after seasonal vaccination (white and red, respectively), measured against a panel of mutant viruses (see Figure 1). The human HI profile is 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 donor’s serum. Bars represent the geometric mean ± geometric SD. Statistical significance was determined between the mutant virus to the respective WT H1 virus data set (before or after vaccination) using Dunn’s corrected Kruskal-Wallis 1-way ANOVA of the mean HI titers (*P ≤ 0.05, ***P ≤ 0.001, ****P ≤ 0.0001). (B) An HI dominance index was calculated for individual samples against each mutant virus (from A). The HI dominance index represents a fold reduction of HI titer in a mutant virus versus its respective WT H1 virus. Single individuals are represented by dotted lines. Averaged HI dominance indices for before (Pre, black) and after (Post, red) vaccination are plotted in solid lines.

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ISSN: 0021-9738 (print), 1558-8238 (online)

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