Breakthrough infections and incomplete vaccine efficacy drive pathogen immune escape.

Abstract

While vaccines effectively reduce disease severity and mortality, their consequences for pathogen immune escape remain poorly understood. Vaccines provide protection through three distinct mechanisms: prevention of infection, reduction of symptoms, and limitation of transmission. When vaccine efficacy is incomplete across multiple dimensions, breakthrough infections in vaccinated individuals may paradoxically increase pathogen escape pressure. This study investigates how vaccine efficacy profiles and coverage levels jointly affect escape pressure. We developed a deterministic compartmental transmission model incorporating three distinct vaccine efficacy parameters: prevention of infection, reduction of symptoms, and limitation of transmission. The model quantifies differential contributions of symptomatic and asymptomatic infections in vaccinated and unvaccinated populations to immune escape pressure. Infection-blocking, symptom-blocking, and transmission-blocking immunity each reduced escape pressure, although no single component alone was sufficient to suppress escape pressure across most conditions. Combinations of efficacy components produced greater reductions. When vaccine efficacy was low across multiple components, increasing coverage could paradoxically elevate escape pressure above pre-vaccination levels. Even in a fully vaccinated population, escape pressure could exceed the pre-vaccination level when infection-blocking and symptom-blocking efficacy were simultaneously low. The effectiveness of symptom-blocking immunity depended on infection-blocking efficacy - when infection-blocking efficacy is low, symptom-blocking efficacy alone did not always suppress escape pressure below pre-vaccination levels. The effect of vaccination on immune escape depends on both vaccine efficacy profiles and coverage levels. Increasing vaccination coverage may increase rather than reduce escape pressure when efficacy is low across multiple dimensions. Combining efficacy across multiple dimensions produced greater reductions in escape pressure than relying on a single efficacy component.