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Immunodominance and Antigenic Variation of Influenza Virus Hemagglutinin: Implications for Design of Universal Vaccine Immunogens.


ABSTRACT: Influenza viruses routinely acquire mutations in their hemagglutinin (HA) and neuraminidase (NA) glycoproteins that abrogate binding of pre-existing antibodies in a process known as antigenic drift. Most human antibodies against HA and NA are directed against epitopes that are hypervariable and not against epitopes that are conserved among different influenza virus strains. Universal influenza vaccines are currently being developed to elicit protective responses against functionally conserved sites on influenza proteins where viral escape mutations can result in large fitness costs [1]. Universal vaccine targets include the highly conserved HA stem domain [2-12], the less conserved HA receptor-binding site (RBS) [13-16], as well as conserved sites on NA [17-19]. One central challenge of universal vaccine efforts is to steer human antibody responses away from immunodominant, variable epitopes and towards subdominant, functionally conserved sites. Overcoming this challenge will require further understanding of the structural basis of broadly neutralizing HA and NA antibody binding epitopes and factors that influence immunodominance hierarchies of human antibody responses.

SUBMITTER: Zost SJ 

PROVIDER: S-EPMC6452323 | biostudies-literature | 2019 Apr

REPOSITORIES: biostudies-literature

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Immunodominance and Antigenic Variation of Influenza Virus Hemagglutinin: Implications for Design of Universal Vaccine Immunogens.

Zost Seth J SJ   Wu Nicholas C NC   Hensley Scott E SE   Wilson Ian A IA  

The Journal of infectious diseases 20190401 Suppl_1


Influenza viruses routinely acquire mutations in their hemagglutinin (HA) and neuraminidase (NA) glycoproteins that abrogate binding of pre-existing antibodies in a process known as antigenic drift. Most human antibodies against HA and NA are directed against epitopes that are hypervariable and not against epitopes that are conserved among different influenza virus strains. Universal influenza vaccines are currently being developed to elicit protective responses against functionally conserved si  ...[more]

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