Waning immunity drives respiratory virus evolution and reinfection

Area of Science:

• Virology
• Immunology
• Evolutionary Biology

Background:

• Viruses exhibit diverse tissue tropisms, with respiratory viruses like influenza and coronaviruses replicating specifically in the respiratory tract, unlike systemic viruses.
• Reinfection by respiratory viruses is often attributed to viral antigenic immune escape, but this doesn't fully explain the prevalence of antigenic variation in these viruses compared to systemic ones.

Purpose of the Study:

• To propose and model a new explanation for the frequent antigenic evolution observed in respiratory viruses.
• To investigate the role of waning immunity in the respiratory tract as a driver of viral antigenic variation.

Main Methods:

• Development of a theoretical model to simulate viral evolution in a partially immune host population.
• Analysis of the conditions under which immune escape variants can invade and replace existing viral strains.

Main Results:

• Waning immunity creates a window where partially immune hosts can be infected by antigenically distinct (heterologous) strains.
• Immune escape variants can invade and spread even if they incur a fitness cost, provided partially immune hosts are sufficiently prevalent.
• The model explains the cyclical emergence and replacement of successive antigenic variants in respiratory viruses.

Conclusions:

• Rapid waning of immunity in the respiratory tract is a key factor promoting antigenic evolution in respiratory viruses.
• This mechanism provides a novel explanation for observed patterns of viral variant succession, complementing existing theories of immune escape.