HA stalk-specific serum total IgG titers were also associated with protection, but this association was attenuated and not statistically significant after adjustment for HA head-specific Ab titers. We found that HA head Abs, as measured by hemagglutinin inhibition (HAI) assays, were associated with protection against naturally acquired H1N1 infection. Here, we quantified H1N1 HA head- and stalk-specific Abs in 179 adults hospitalized during the 2015–2016 influenza virus season. Although HA stalk Abs can provide protection in animal models, it is unknown if they are present at sufficient levels in humans to provide protection against naturally acquired influenza virus infections. There is great interest in developing new universal immunization strategies that elicit broadly neutralizing Abs against conserved regions of HA, such as the stalk domain. Anti-HA head Abs can be highly potent, but they have limited breadth since the HA head is variable. Most neutralizing antibodies (Abs) elicited by influenza viruses target the head domain of the hemagglutinin (HA) protein. Seasonal influenza viruses are a major cause of human disease worldwide.
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