The immunodominance of antigenic site Sb on the H1 influenza virus hemagglutinin increases with high immunoglobulin titers of the cohorts and with young age, but not sex.

The head domain of the hemagglutinin of influenza viruses plays a dominant role in the antibody response due to the presence of immunodominant antigenic sites that are the main targets of host neutralizing antibodies. For the H1 hemagglutinin, five major antigenic sites defined as Sa, Sb, Ca1, Ca2, and Cb have been described. Although previous studies have focused on defining the hierarchy of the antigenic sites of the hemagglutinin in different human cohorts, it is still unclear if the immunodominance profile of the antigenic sites might change with the antibody levels of individuals or if other demographic factors (such as exposure history, sex, or age) could also influence the importance of the antigenic sites. The major antigenic sites of influenza viruses hemagglutinins are responsible for eliciting most of the hemagglutination inhibition antibodies in the host. To determine the antibody prevalence towards each major antigenic site, we evaluated the hemagglutination inhibition against a panel of mutant H1 viruses, each one lacking one of the "classic" antigenic sites. Our results showed that the individuals from the Stop Flu NYU cohort had an immunodominant response towards the sites Sb and Ca2 of H1 hemagglutinin. A simple logistic regression analysis of the immunodominance profiles and the hemagglutination inhibition titers displayed by each donor revealed that individuals with high hemagglutination inhibition titers against the wild-type influenza virus exhibited higher probabilities of displaying an immunodominance profile dominated by Sb, followed by Ca2 (Sb > Ca2 profile), while individuals with low hemagglutination inhibition titers presented a higher chance of displaying an immunodominance profile in which Sb and Ca2 presented the same level of immunodominance (Sb = Ca2 profile). Finally, while age exhibited an influence on the immunodominance of the antigenic sites, biological sex was not related to displaying a specific immunodominance profile.
Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: [The Icahn School of Medicine at Mount Sinai has filed patent application entitle “Mosaic influenza virus hemagglutinin polypeptides and uses thereof” which list Florian Krammer, Peter Palese, and Weina Sun as co-inventors. Florian Krammer has consulted for Merck, Seqirus, Curevac and Pfizer, and is currently consulting for GSK, Gritstone, 3rd Rock Ventures and Avimex and he is a co-founder and scientific advisory board member of CastleVax. The Krammer laboratory is also collaborating with Pfizer on animal models of SARS-CoV-2 and Dynavax on influenza virus vaccines. Mark J. Mulligan reported laboratory research and clinical trials contracts for vaccines or MAB with Lilly, Pfizer, and Sanofi; personal fees for Scientific Advisory Board service from Merck, Meissa Vaccines, Inc. and Pfizer. All other authors have declared that no conflict of interest exists.].
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