Enterovirus A71 2A-S125A acts as an attenuated vaccine candidate, indicating a universal approach in developing enterovirus vaccines.
J Med Virol
; 96(8): e29838, 2024 Aug.
Article
en En
| MEDLINE
| ID: mdl-39081166
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.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Vacunas Atenuadas
/
Vacunas Virales
/
Carga Viral
/
Enterovirus Humano A
/
Infecciones por Enterovirus
/
Anticuerpos Neutralizantes
/
Anticuerpos Antivirales
Límite:
Animals
/
Female
/
Humans
Idioma:
En
Revista:
J Med Virol
/
J. med. virol
/
Journal of medical virology
Año:
2024
Tipo del documento:
Article
País de afiliación:
China