The post-2009 influenza pandemic era: time to revisit antibody immunodominance
Kristien Van Reeth
Kristien Van Reeth
Published November 1, 2018; First published October 8, 2018
Citation Information: J Clin Invest. 2018;128(11):4751-4754. https://doi.org/10.1172/JCI124151.
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Category: Commentary

The post-2009 influenza pandemic era: time to revisit antibody immunodominance

Abstract

The current inactivated influenza vaccines rely on the induction of neutralizing antibodies against the head domain of the viral hemagglutinin (HA). The HA head contains five immunodominant antigenic sites, all of which are subject to antigenic drift, thereby limiting vaccine efficacy. Bypassing the immune system’s tendency to focus on the most variable regions of the HA may be a step toward more broadly protective influenza vaccines. However, this requires a better understanding of the biological meaning of immunodominance, and of the hierarchy between different antigenic sites. In this issue of the JCI, Liu et al. determined the immunodominance of the five antigenic sites of the HA head in experimentally infected mice, guinea pigs, and ferrets. All three species exhibited different preferences for the five sites of the 2009 pandemic H1N1 strain. Moreover, human subjects exhibited yet a different pattern of immunodominance following immunization with the standard inactivated influenza vaccine. Together, these results have important implications for influenza vaccine design and interpretation of animal models.

Authors

Kristien Van Reeth

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Figure 1

Schematic of influenza HA structure and variability.

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Schematic of influenza HA structure and variability. (A) Schematic repre...
(A) Schematic representation of the structure of the H1N1 HA protein with its head and stalk domain. The HA head contains five immunodominant antigenic sites, designated Sa, Sb, Ca1, Ca2, and Cb. For the Sa and Sb sites, the S stands for strain-specific. These sites are most variable and are in close proximity to the receptor binding site. The C sites are cross-reactive sites that are less variable between H1N1 strains and are located further downward on the HA. (B) HA head epitopes that are outside the classical antigenic sites and, in particular, epitopes in the HA stalk are more conserved among different influenza A viruses. These sites are targeted to a much lower degree by antibody-producing B cells. (C) Influenza virus particle with HA and NA protruding from the surface. The combination of HA and NA proteins determines the subtype of the virus, such as H1N1, H5N1, etc.