Getting the upper-hand on Covid-19
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The development of rationally engineered severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccines based on a modified live virus (MLV) platform was the focus of an online talk by Professor Nikolaus Osterrieder at City University of Hong Kong (CityU) on 8 October.
Under experimental conditions, the platform offers efficacy against all current variants of the virus, which causes coronavirus disease-19, or Covid-19; is exquisitely safe; and easy to produce and store, according to Professor Osterrieder, Dean of the Jockey Club College of Veterinary Medicine and Life Sciences and Chair Professor of Virology and One Health in the Department of Infectious Diseases and Public Health.
His talk was titled “After the vaccination is before the vaccination – how we maintain the upper hand on SARS-CoV-2” and was part of the President’s Lecture Series: Excellence in Academia series.
“Vaccines are a cornerstone of global public health and have resulted in the control and even extinction of many deadly diseases in humans and animals,” said Professor Osterrieder, a world expert on virology.
He added that, given that the world will have to learn to live with the virus and the many variants that are discovered at ever increasing speed, vaccine development and use cannot stop.
After summarising the current global situation concerning vaccination work aimed at curtailing the spread of SARS-CoV-2, issues surrounding the sluggish uptake of vaccination among some populations, variants of the virus, and the absence of vaccination for much of Africa, Professor Osterrieder introduced his team’s research into the advantages of modified live virus vaccines (MLV).
MLVs are made up of attenuated microorganisms that reproduce in vivo to initiate a response from the body’s immune system very much like natural infection but minus the symptoms that might be seen in natural exposure to the virus.
The advantages of MLVs include broader and longer-lasting immune response compared to inactivated/vectored mRNA vaccines; ease of production and storage at room temperature.
The technique used in developing the MLVs by Professor Osterrieder and his collaborators is codon pair deoptimisation (CPD), which is an efficient strategy for reducing the negative effects of a virus.
The attenuation of viruses (and other pathogens) to the desired level in a controlled and predictable manner is managed by introducing “nucleotide mutations into coding sequences without changing the amino acid composition of proteins”.
The strategy involves “synthetic recoding of viral genomes that alters the positions of synonymous codons, thereby increasing the number of suboptimal codon pairs and CpG dinucleotides in recoded genomes”.
Experiments on hamsters have shown that CPD attenuates SARS-CoV-2. The vaccination protects hamsters against infection: there is induction of robust immune responses, no weight loss and no signs of tissue damage.
“The technique also appears to protect against known SARS-CoV-2 variants,” said Professor Osterrieder, adding that the continued development and promotion of vaccines was an imperative.
“Vaccines have saved countless lives, and our modern and highly interconnected world is unthinkable without their protection,” he said.