Heads, stalks and everything else: how can antibodies eradicate influenza as a human disease?

Abstract

Current seasonal influenza virus vaccines are effective against infection but they have to be reformulated on a regular basis to counter antigenic variations. The majority of the antibodies induced in response to seasonal vaccination are strain-specific. However, antibodies targeting conserved epitopes on the hemagglutinin protein have been identified and they offer broad protection. Most of these antibodies bind the hemagglutinin stalk domain and are generated from preexisting memory B cells. Broadly protective stalk-biased responses induced by antigenically divergent influenza strains, in concert with prior immunity, are sufficient to eradicate seasonally circulating strains. Future vaccine trials should aim to harness and maintain such a response with the realistic goal of developing a universal influenza vaccine.

Effect of Priming With Seasonal Influenza A(H3N2) Virus on the Prevalence of Cross-Reactive Hemagglutination-Inhibition Antibodies to Swine-Origin A(H3N2) Variants

“…Consistent with previous findings [36, 37, 44], our data indicated that primary exposure with sH3N2 viruses influenced HI antibody response thereafter. Because HI antibodies target the HA globular head and neutralizing antibodies target both globular head and stalk domain [45], it would also be interesting to investigate to what extent such primary exposure with sH3N2 virus affects the neutralizing antibody response.…”

1st Workshop of the Canadian Society for Virology

“…The discovery of bnAbs that target the highly-conserved stalk domain of hemagglutinin have raised hopes for vaccines capable of conferring “universal” immunity against influenza viruses. These antibodies are normally made in low quantities, but can be substantially boosted through exposure to “pandemic-like” hemagglutinin (HA) proteins [25,26,27], and by overcoming the immunodominance of HA head domains [28]. By focusing research efforts on natural, polyclonal responses, Dr. Miller has discovered that both antibody isotype and specificity have major consequences on bnAb function.…”

The Impact of Bioinformatics on Vaccine Design and Development

“…The globular head of HA contains the receptor binding site and the majority of the antigenic sites; consequently, this region is also the most variable. The stem region contains the fusion peptide and, although it previously was not considered a target for vaccine development, the discovery of neutralizing antibodies aimed at this region revealed its potential in vaccine design [52,56]. Several conserved regions have been described in the stem region of HA [57], which make a universal vaccine a possibility.…”