Comprehensive profiling of neutralizing polyclonal sera targeting coxsackievirus B3.

Area of Science:

• Virology
• Immunology
• Structural Biology

Background:

• Polyclonal neutralizing antibodies are vital for clearing viral infections.
• The precise mechanisms by which these antibodies target non-enveloped viruses, such as picornaviruses, are not fully understood.
• Understanding antibody-epitope interactions is key to predicting viral immune escape.

Purpose of the Study:

• To comprehensively profile the antigenic targets of human and mouse polyclonal sera against coxsackievirus B3.
• To identify factors predicting viral escape from neutralizing antibody responses.
• To assess epitope dominance and immune escape dynamics at a population level.

Main Methods:

• Generation of full antigenic profiles for human and mouse polyclonal sera targeting coxsackievirus B3 capsid.
• Analysis of structural and evolutionary parameters associated with viral escape.
• Assessment of epitope dominance and the mutational requirements for immune escape.

Main Results:

• Significant variation observed in the breadth and strength of neutralization sites targeted by individual human polyclonal responses.
• Homogenous neutralization responses were observed in experimentally infected mice, contrasting with human responses.
• At least two mutations are required for significant viral escape from multiple polyclonal sera.

Conclusions:

• Human polyclonal antibody responses exhibit diverse targeting of viral capsids, unlike homogenous mouse responses.
• Key structural and evolutionary parameters can predict viral escape from antibody neutralization.
• This study provides insights into immune dominance and escape mechanisms for non-enveloped viruses at a population level.