A vaccine that fully protects mice against a lethal dose of MERS-CoV, the coronavirus that causes Middle East respiratory syndrome (MERS) is being used by its developers at the University of Iowa (UI) and the University of Georgia as the foundation for a vaccine candidate against the pandemic SARS-CoV-2 virus, which is a close cousin to MERS-CoV.
The parainfluenza virus (PIV5)-based MERS vaccine is engineered to express the MERS-CoV envelope spike (S) protein that mediates viral entry into target cells. Preclinical in vivo tests with the vaccine in mice are reported in mBio, and demonstrated that just one, relatively low dose of the vaccine given to animals intranasally fully protected all the treated mice from a lethal dose of MERS coronavirus, and improved virus clearance in the lungs.
The researchers, headed by Paul McCray, MD, a professor of pediatrics at the UI Carver College of Medicine, and Biao He, PhD, at the University of Georgia College of Veterinary Medicine, have now used this vaccine design as the basis for a candidate vaccine that expresses the SARS-Co-2 spike protein. “Our new study indicates that PIV5 may be a useful vaccine platform for emerging coronavirus diseases, including SARS-CoV-2, the virus causing the ongoing COVID-19 pandemic,” said McCray. “Using the same strategy, vaccine candidates based on PIV5 expressing the spike protein of SARS-CoV-2 have been generated. We are planning more studies in animals to test the ability of PIV5-based vaccines in preventing disease caused by SARS-CoV-2.”
The team reported on its tests with the MERS vaccine candidate in an mBio paper, released today, and titled “Single-Dose, Intranasal Immunization with Recombinant Parainfluenza Virus 5 Expressing Middle East Respiratory Syndrome Coronavirus (MERS-CoV) Spike Protein Protects Mice from Fatal MERS-CoV Infection.”
MERS and COVID-19 coronavirus infections can both lead to severe lung disease and acute respiratory distress syndrome (ARDS). MERS is deadlier than COVID-19, in the sense that it is fatal in about one-third of known cases. However, while there have been 2,494 WHO-reported MERS cases and 858 deaths since 2012, when the virus first emerged, there have been over 1.25 million confirmed cases of COVID-19 worldwide since it first emerged in late 2019 in Wuhan, China, and almost 70,000 people have died from COVID-19.
There is no vaccine or antiviral therapeutic current available against MERS or COVID-19. For their vaccine research, the researchers developed a MERS candidate comprising a PIV5 viral vector that expressed the MERS-CoV viral envelope S protein. This protein consists of an S1 subunit that binds to the virus receptor dipeptidyl peptidase 4 (DPP4, or CD26), via a receptor-binding domain (RBD), and an S2 subunit that mediates membrane fusion, the authors explained. “Thus, the S protein, particularly the RBD, is an important target for MERS-CoV vaccine development.”
Having tested that the virus construct expressed S protein when used to infect lab-grown cells, the researchers carried out in vivo experiments with the PIV-5-MERS-S vaccine in mice engineered to carry the human DPP4 receptor. They found that all the animals given a single intranasal dose were protected against a lethal challenge with MERS-CoV, whereas all the control animals died following viral challenge.
When the team analyzed the immune responses generated by the vaccine, they found that both antibodies and protective T cells were produced. However, the antibody response was only modest, and it seems most likely that the vaccine’s protective effect is due to the T cell response in the mouse lungs. The results collectively indicated that PIV5-MERS-S immunization resulted in a significantly increased, MERS-S-specific CD8 T cell response. “The finding that PIV5 expressing MERS S protected mice against lethal MERS-CoV challenge at a single low dose of 104 PFU suggests its potential use as a vaccine vector for emerging viruses such as SARS-CoV-2,” the team concluded. “Further studies of using PIV5 expressing the S protein from SARS-CoV-2 as a vaccine candidate are ongoing.”
The researchers noted several factors that make PIV5 expressing a coronavirus spike protein an appealing platform for vaccine development against emerging coronaviruses. PIV5 can infect many different mammals, including humans, without causing disease, and is also being investigated as a vaccine vector for other respiratory diseases, including respiratory syncytial virus (RSV) and influenza. The fact that a low dose of the vaccine was sufficient to protect the mice might be beneficial with a view to creating enough vaccine for mass immunization. The MERS vaccine in the reported current study was, in addition, the most effective MERS vaccine to date in animal models of the disease.
