Open AccessMiddle East respiratory syndrome coronavirus vaccine based on a propagation-defective RNA replicon elicited sterilizing immunity in mice
Author(s) -
Javier Gutiérrez-Álvarez,
José M. Honrubia,
Alejandro Sanz-Bravo,
Ezequiel González-Miranda,
Raúl FernándezDelgado,
María Teresa Rejas,
Sonia Zúñiga,
Isabel Sola,
Luis Enjuanes
Publication year - 2021
Publication title -
proceedings of the national academy of sciences of the united states of america
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.011
H-Index - 771
eISSN - 1091-6490
pISSN - 0027-8424
DOI - 10.1073/pnas.2111075118
Subject(s) - replicon , biology , virology , attenuated vaccine , rna , arterivirus , viral replication , gene , virus , plasmid , genetics , virulence , infectious disease (medical specialty) , medicine , disease , covid-19 , pathology
Significance Coronaviruses (CoVs) have the largest genome among RNA viruses and a proofreading exoribonuclease (nsp14) responsible for high-fidelity RNA synthesis. These properties make CoVs very attractive for the establishment of vaccine platforms or viral vectors since they can stably store large amounts of information without genome integration. Using Middle East respiratory syndrome coronavirus (MERS-CoV) as a model, a propagation-deficient RNA replicon was generated by removing the envelope (E) gene (essential for viral morphogenesis and involved in virulence) and accessory genes 3, 4a, 4b, and 5 (responsible for antagonism of the innate immune response): MERS-CoV-Δ[3,4a,4b,5,E]. This replicon is strongly attenuated and elicits sterilizing protection after a single immunization, making it a promising vaccine candidate and an interesting platform for vector-based vaccine development.