Middle East respiratory syndrome coronavirus vaccine based on a propagation-defective RNA replicon elicited sterilizing immunity in mice.
Proc Natl Acad Sci U S A
; 118(43)2021 10 26.
Article
in English
| MEDLINE | ID: covidwho-1481965
ABSTRACT
Self-amplifying RNA replicons are promising platforms for vaccine generation. Their defects in one or more essential functions for viral replication, particle assembly, or dissemination make them highly safe as vaccines. We previously showed that the deletion of the envelope (E) gene from the Middle East respiratory syndrome coronavirus (MERS-CoV) produces a replication-competent propagation-defective RNA replicon (MERS-CoV-ΔE). Evaluation of this replicon in mice expressing human dipeptidyl peptidase 4, the virus receptor, showed that the single deletion of the E gene generated an attenuated mutant. The combined deletion of the E gene with accessory open reading frames (ORFs) 3, 4a, 4b, and 5 resulted in a highly attenuated propagation-defective RNA replicon (MERS-CoV-Δ[3,4a,4b,5,E]). This RNA replicon induced sterilizing immunity in mice after challenge with a lethal dose of a virulent MERS-CoV, as no histopathological damage or infectious virus was detected in the lungs of challenged mice. The four mutants lacking the E gene were genetically stable, did not recombine with the E gene provided in trans during their passage in cell culture, and showed a propagation-defective phenotype in vivo. In addition, immunization with MERS-CoV-Δ[3,4a,4b,5,E] induced significant levels of neutralizing antibodies, indicating that MERS-CoV RNA replicons are highly safe and promising vaccine candidates.
Keywords
Full text:
Available
Collection:
International databases
Database:
MEDLINE
Main subject:
Replicon
/
RNA, Viral
/
Viral Vaccines
/
Coronavirus Infections
/
Middle East Respiratory Syndrome Coronavirus
Type of study:
Experimental Studies
Topics:
Vaccines
Limits:
Animals
/
Female
/
Humans
Language:
English
Year:
2021
Document Type:
Article
Affiliation country:
Pnas.2111075118
Similar
MEDLINE
...
LILACS
LIS