Enterovirus A71 2A‐S125A acts as an attenuated vaccine candidate, indicating a universal approach in developing enterovirus vaccines

Abstract

Enteroviruses are important human pathogens with diverse serotypes, posing a major challenge to develop vaccines for individual serotypes, the success of polio vaccines in controlling and eradicating polio, along with the recent emergence and high prevalence of enterovirus‐caused infectious diseases, highlights the importance of enterovirus vaccine development. Given our previous report on enteroviruses weakened by the 2 A S/T125A mutation, we assessed the potential of the EV‐A71 2A‐125A mutant as a vaccine candidate to address this challenge. We found that the 2A‐125A mutant caused transient mild symptoms, low viral loads, and no significant pathological changes mild pathological changes in hSCARB2‐KI mice, producing long‐lasting cross‐neutralizing antibodies against two EV‐A71 wild strains. Pre‐exposure to the 2A‐125A mutant substantially protected against the EV‐A71 Isehara wild‐type strain, causing minor pathologies, significantly reducing muscle and lung inflammation, and preventing neurological damage, with reduced viral loads in vivo. Pre‐exposure also distinctly suppressed the expression of pro‐inflammatory cytokines, correlating to the severity of clinical symptoms. Collectively, the EV‐A71 2A‐125A mutant was attenuated and could generate a robust and protective immune response, suggesting its potential as a vaccine candidate and global solution for specific enterovirus vaccine development.