Antibody Immunodominance: The Key to Understanding Influenza Virus Antigenic Drift

Abstract

Influenza A virus (IAV) imposes a significant socioeconomic burden on humanity. Vaccination is effective in only 60% of individuals, even under optimal circumstances. The difficulty stems from the remarkable ability of IAV to evade existing immunity. IAV's error prone polymerase enables the rapid antigenic evolution of the two virion surface glycoproteins, neuraminidase and hemagglutinin (HA). Since the most potent antibodies (Abs) at neutralizing viral infectivity are directed the head of the HA, amino acid substitutions in this region enable IAV to evade Ab-based immunity. Here, we review recent progress in understanding how immunodominance, the tendency of the immune system to respond to foreign immunogens in a hierarchical manner, shapes IAV evolution.

Keywords: antibody immunodominance; antigenic drift; influenza A virus; vaccines.

FIG. 1.

Pattern of ID to IAV virion. Cartoon of virus showing the structural proteins as indicated. Table shows the relative abundance of surface and internal proteins (27). The relative ID of serum Abs in response to infection and immunization is not linearly related to the copy number of virion of proteins. Ab, antibody; HA, hemagglutinin; IAV, influenza A virus; ID, immunodominance; NA, neuraminidase.

FIG. 2.

Defined antigenic sites on PR8 HA. Sites defined by mAb escape mutant selection (7) are shown on the HA structure (PDB 1RU7) (18). Each monomer in the native trimer is colored purple. Bound sialic acid is shown in green. Antigenic sites: Sa, yellow; Sb, red; Ca1, white; Ca2, black; Cb, pink. Sa and Sb sites are strain specific, while Ca and Cb sites are shared by some drifted variants. Left, trimer, as it would appear looking at virion from top. Right, side view of trimer. Note that the transmembrane domain is not present in the solved structure.