These changes accumulate over time, transforming the viruses and allowing them to escape host recognition without hindering their ability to gain entry to cells. Antigenic drift occurs when influenza viruses continuously undergo changes to their HA and NA surface proteins through mutation. This poses a challenge for vaccine formulation because evolutionary changes in these proteins enable the virus to evade the adaptive immune response through a combination of phenomena known as antigenic drift and shift (1), as shown in Figure 1. Most influenza vaccines elicit antibodies against the major viral surface proteins, hemagglutinin (HA) and neuraminidase (NA). Here, I’ll explore the challenges associated with flu vaccine development – and the emerging technologies hoping to tackle them. The most effective preventative measure against flu is vaccination. Alongside seasonal outbreaks (which tend to prevail over the winter months) there is also the looming threat of pandemic influenza strains, which have the potential to bring healthcare systems to a standstill because most people have little or no immunity. 2018 92:e00859-18.Influenza viruses A and B are a major public health concern, mainly affecting the pharynx, trachea, and sometimes the lungs of millions of people worldwide each year, with symptoms that range from mild to life-threatening. Sera from individuals with narrowly focused influenza virus antibodies rapidly select viral escape mutations in ovo. Defining influenza A virus hemagglutinin antigenic drift by sequential monoclonal antibody selection. Fitness costs limit influenza A virus hemagglutinin glycosylation as an immune evasion strategy. Defining B cell immunodominance to viruses. 2019 10:e00204-19.Īngeletti D., Gibbs J.S., Angel M., Kosik I., Hickman H.D., Frank G.M., Das S.R., Wheatley A.K., Prabhakaran M., Leggat D.J., et al. Human Influenza A Virus Hemagglutinin Glycan Evolution Follows a Temporal Pattern to a Glycan Limit. Note that in the Figure, the yellow mutant is less fit in non-immune host (losing the competition to the other mutants) but much more fit when Ab neutralization is added to the various selection factors.Īltman M.O., Angel M., Košík I., Trovão N.S., Zost S.J., Gibbs J.S., Casalino L., Amaro R.E., Hensley S.E., Nelson M.I., Yewdell J.W. In the latter case, this will be a very infrequent event because so few viruses are transmitted, but given enough transmission events to immune individuals, it can contribute to antigenic drift. Ab selection can occur either in the transmitting host or the recipient host. In the presence of neutralizing Abs, viruses with mutations that enable escape from neutralization are rapidly selected, resulting in antigenic drift. This results in the steady accumulation of mutants as a virus circulates. Genetic versus antigenic drift Nearly every virus generated in a host (depicted as a metaphorical bottle) possesses at least one point mutation. Transmission of a very limited number of viruses between hosts (bottlenecking, 5 different mutants in the figures) results in the random selection of mutants that compete in the new host (generating a hierarchy as shown, with the blue virus becoming extinct with the purple virus at the top), all the while generating a new repertoire of mutants that are bottlenecked in transmitting to the next host.
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