Development of Self-Replicating Propagation-Defective RNAs as Next Generation Vaccine Candidates Against Human Coronaviruses

C.E. Credits: P.A.C.E. CE Florida CE
Speaker

Abstract

Self-amplifying RNA replicons are promising candidates for next generation vaccines against human coronaviruses with pandemic potential. Self-amplification of RNAs in host cells generates more potent immune
responses with significantly reduced amounts of RNA delivered. Their defects in essential functions for viral dissemination make them highly safe as vaccines. We have shown that the deletion of the envelope (E) gene from Middle East respiratory syndrome coronavirus (MERS-CoV) led to a replication-competent propagation-defective RNA replicon (MERS-CoV-ΔE) that does not produce infectious progeny and behaves as a safe single-cycle virus in cell cultures and in vivo. The combined deletion of E gene with accessory proteins 3, 4a, 4b and 5, which are involved in the interference with the innate immune response, further attenuated the propagation-defective RNA replicon in vivo, in a mouse model of infection. 


Inside the cells, in the absence of E protein, MERS RNA replicons formed highly immunogenic polymeric structures. Intranasal administration of MERS-CoV RNA replicons to mice provided 100% protection after challenge with a lethal dose of virulent MERS-CoV. Interestingly, they induced sterilizing immunity, as no infectious virus was detected in the lungs of challenged mice. These results represent a proof of concept for the development of safe and effective RNA replicon vaccines against deadly human CoVs. We are currently developing replication-competent propagation-defective RNA replicons derived from SARS-CoV-2 as safe and more efficient vaccine candidates, since they simultaneously express multiple viral antigens.

LEARNING OBJECTIVES

1.    Define the potential of self-amplifying RNA replicons derived from coronaviruses as vaccine candidates.
2.    Explain current approaches to the development of RNA-replicon vaccine candidates against SARS-CoV-2.


Show Resources
You May Also Like
MAY 11, 2021 10:00 AM PDT
C.E. CREDITS
MAY 11, 2021 10:00 AM PDT
Date: May 11, 2021 Time: 10:00zm PDT Your samples are some of the most valuable assets in the laboratory. After spending countless hours on extraction and preparation, your conclusions could...
SEP 14, 2021 7:00 AM PDT
C.E. CREDITS
SEP 14, 2021 7:00 AM PDT
Date: September 14, 2021 Time: 7am PDT, 10am EDT, 4pm CEST A conventional thermal cycler has long been a commodity product in the lab and end-point PCR techniques can be completed almost wit...
JUN 09, 2021 7:00 AM PDT
C.E. CREDITS
JUN 09, 2021 7:00 AM PDT
Date: June 9, 2021 Time: 09 June 2021, 7am PDT, 10am EDT, 4pm CEST cells with dramatic implications on the validity of past cell culture related research. The fact that at least 509 cell lin...
SEP 17, 2021 12:00 PM CST
C.E. CREDITS
SEP 17, 2021 12:00 PM CST
Date: September 16, 2021 Time: 9:00pm (PDT), 12:00am (EDT) 3D cellular models like organoids and spheroids offer an opportunity to better understand complex biology in a physiologically rele...
APR 21, 2021 10:00 AM PDT
C.E. CREDITS
APR 21, 2021 10:00 AM PDT
Date: April 21, 2021 Time: 10:00am (PDT), 1:00pm (EDT) Serological testing for SARS-CoV-2 has been steadily adopted into clinical practice over the course of this pandemic. In this webinar,...
JUN 08, 2021 9:00 AM PDT
JUN 08, 2021 9:00 AM PDT
Date: June 8, 2021 Time: 9:00am PDT Reducing the spread of highly infectious and deadly diseases within the population, vaccine development is crucial in saving millions of lives each year....
Loading Comments...
Show Resources