Neutralizing antibodies targeting a novel epitope on envelope protein exhibited broad protection against flavivirus without risk of disease enhancement.
J Biomed Sci
; 30(1): 41, 2023 Jun 14.
Article
en En
| MEDLINE
| ID: mdl-37316861
ABSTRACT
BACKGROUND:
Flavivirus causes many serious public health problems worldwide. However, licensed DENV vaccine has restrictions on its use, and there is currently no approved ZIKV vaccine. Development of a potent and safe flavivirus vaccine is urgently needed. As a previous study revealed the epitope, RCPTQGE, located on the bc loop in the E protein domain II of DENV, in this study, we rationally designed and synthesized a series of peptides based on the sequence of JEV epitope RCPTTGE and DENV/ZIKV epitope RCPTQGE.METHODS:
Immune sera were generated by immunization with the peptides which were synthesized by using five copies of RCPTTGE or RCPTQGE and named as JEV-NTE and DV/ZV-NTE. Immunogenicity and neutralizing abilities of JEV-NTE or DV/ZV-NTE-immune sera against flavivirus were evaluated by ELISA and neutralization tests, respectively. Protective efficacy in vivo were determined by passive transfer the immune sera into JEV-infected ICR or DENV- and ZIKV-challenged AG129 mice. In vitro and in vivo ADE assays were used to examine whether JEV-NTE or DV/ZV-NTE-immune sera would induce ADE.RESULTS:
Passive immunization with JEV-NTE-immunized sera or DV/ZV-NTE-immunized sera could increase the survival rate or prolong the survival time in JEV-challenged ICR mice and reduce the viremia levels significantly in DENV- or ZIKV-infected AG129 mice. Furthermore, neither JEV -NTE- nor DV/ZV-NTE-immune sera induced antibody-dependent enhancement (ADE) as compared with the control mAb 4G2 both in vitro and in vivo.CONCLUSIONS:
We showed for the first time that novel bc loop epitope RCPTQGE located on the amino acids 73 to 79 of DENV/ZIKV E protein could elicit cross-neutralizing antibodies and reduced the viremia level in DENV- and ZIKV-challenged AG129 mice. Our results highlighted that the bc loop epitope could be a promising target for flavivirus vaccine development.Palabras clave
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Virus Zika
/
Infección por el Virus Zika
Tipo de estudio:
Etiology_studies
/
Risk_factors_studies
Límite:
Animals
Idioma:
En
Revista:
J Biomed Sci
Asunto de la revista:
MEDICINA
Año:
2023
Tipo del documento:
Article
País de afiliación:
Taiwán