Different genetic barriers for resistance to HA stem antibodies in influenza H3 and H1 viruses.
basic_science · Level V
Where this comes from
- Record sourced from PubMed, PMID 32554590.
- Also identified by DOI 10.1126/science.aaz5143 and PMC identifier 7412937.
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Abstract
The discovery and characterization of broadly neutralizing human antibodies (bnAbs) to the highly conserved stem region of influenza hemagglutinin (HA) have contributed to considerations of a universal influenza vaccine. However, the potential for resistance to stem bnAbs also needs to be more thoroughly evaluated. Using deep mutational scanning, with a focus on epitope residues, we found that the genetic barrier to resistance to stem bnAbs is low for the H3 subtype but substantially higher for the H1 subtype owing to structural differences in the HA stem. Several strong resistance mutations in H3 can be observed in naturally circulating strains and do not reduce in vitro viral fitness and in vivo pathogenicity. This study highlights a potential challenge for development of a truly universal influenza vaccine.
Medical subject headings
- Antibodies, Neutralizing
- Antibodies, Viral
- Hemagglutinin Glycoproteins, Influenza Virus
- Immune Tolerance
- Influenza A Virus, H1N1 Subtype
- Influenza A Virus, H3N2 Subtype