Abstract
The antigenic drift theory states that influenza evolves via the gradual accumulation of mutations, decreasing a host’s immune protection against previous strains. Influenza vaccines are designed accordingly, under the premise of antigenic drift. However, a paradox exists at the centre of influenza research. If influenza evolved primarily through mutation in multiple epitopes, multiple influenza strains should co-circulate. Such a multitude of strains would render influenza vaccines quickly inefficacious. Instead, a single or limited number of strains dominate circulation each influenza season. Unless additional constraints are placed on the evolution of influenza, antigenic drift does not adequately explain these observations. Here, we explore the constraints placed on antigenic drift and a competing theory of influenza evolution – antigenic thrift. In contrast to antigenic drift, antigenic thrift states that immune selection targets epitopes of limited variability, which constrain the variability of the virus. We explain the implications of antigenic drift and antigenic thrift and explore their current and potential uses in the context of influenza vaccine design.
Highlights
We present two theories describing the antigenic evolution of influenza: the well-known antigenic drift theory, alongside the antigenic thrift theory
If broadly reactive antibodies similar to those identified in Whittle et al and Nogales et al are commonly found in the human population, as suggested by other studies [64], the sites they bind to could be the epitopes of limited variability outlined in the antigenic thrift theory
The focus of many of these approaches is to avoid variable parts of the influenza virus. The rationale for these approaches is that targeting more conserved parts may allow a single vaccine to protect against a large number of current and future influenza strains
Summary
Publisher’s Note: MDPI stays neutral with regard to jurisdictional claims in published maps and institutional affiliations. New subtypes emerge via antigenic shift, known as genetic reassortment, by which two different subtypes combine to form a third novel subtype [15,16] This is most likely to occur in swine, which are susceptible to both avian and human influenza, as it expresses both 20 6 and 20 3 sialic acid, found in humans and birds, respectively [17]. We describe the theories underlying the design of current influenza vaccines (both universal and seasonal) in the context of immune responses to influenza virus antigens. We present antigenic drift and thrift-based models for universal influenza vaccine design as an alternative to the current prevailing approaches [31,32]
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
