Updated: April 29, 2021 2:12:50 pm
Using a new platform, scientists have developed a Covid-19 vaccine that they say could offer protection against not only existing and future strains of the SARS-CoV-2 coronavirus, but also other coronaviruses. The vaccine is cheap, at $1 a dose, and has shown promising results in early animal testing, the researchers have reported in the journal PNAS.
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How it’s different
The new vaccine-production platform was invented by Dr Steven L Zeichner of the University of Virginia Health System (UVA). It involves synthesising DNA that directs the production of a piece of the virus. This can instruct the immune system how to mount an immune response against the virus.
The vaccine, created by Zeichner and Virgina Tech’s Dr Xiang-Jin Meng, targets a part of the virus’s spike protein called the fusion peptide. This compound is essentially universal among coronaviruses, and has not been observed to differ at all in the many genetic sequences of SARS-CoV-2 obtained from around the world, the researchers said.
“Other Covid-19 vaccines do not appear to be specifically targeting the fusion peptide, to my knowledge,” Zeichner said, in response to an emailed question. “Most vaccines in development target either the entire spike protein, or just the receptor binding domain (RBD).”
While antibodies against the RBD can provide good neutralising activity, there can be mutations in the RBD that decrease somewhat the effectiveness of the antibodies, he said. “I think that making a vaccine that essentially recapitulates almost exactly the antigens made by the virus may be mistaken. The virus has evolved to be able to continue to live even in the presence of an immune response. In a sense, making a vaccine that elicits an immune response against an immunodominant antigen may be ‘falling for’ the ‘tricks’ that the virus has laid out for us,” he said.
How it works
There are other vaccines that instruct the creation of a part of the virus. For example, mRNA vaccines such as those developed by Pfizer-BioNTech and Moderna, both in use in the US, deliver mRNA (messenger RNA) carrying instructions for creating the spike protein of the coronavirus. The idea is that when the real virus attacks, the immune system will recognise the spike and mount a response.
How similar, then, is the new DNA-based platform that delivers instructions encoding for the fusion peptide? It is quite different from mRNA, Zeichner said. In the new platform, once DNA encoding for the fusion peptide has been synthesised, it is inserted into another small circle of DNA, called a plasmid, which can reproduce within bacteria. The DNA plasmid is introduced into bacteria; this technique uses the bacteria E coli.
“To make our vaccine, we grow the E coli, then inactivate it with formalin,” Zeichner said. “… Growing bacteria and inactivating them is a well-developed process, and the factories that can do this already exist in many countries around the world. The killed whole-cell cholera vaccines can be made for <US$1/dose, which can serve as a kind of benchmark. Growing bacteria and inactivating them is easier and much less expensive that making large quantities of mRNA.”
Tests & results
Meng and Zeichner made two vaccines, one designed to protect against Covid-19, and another designed to protect against porcine epidemic diarrhoea virus (PEDV). The latter, which infects pigs, is also a coronavirus. When PEDV first appeared in pig herds in the US, it killed almost 10% of pigs in the country.
Both vaccines were found to protect the pigs against illness caused by PEDV. The vaccines did not prevent infection, but protected the pigs from developing severe symptoms.
The researchers acknowledged that additional testing — including human trials —would be required before their Covid-19 vaccine could be approved by regulatory agencies around the world for use in people.
But what if the fusion peptide of SARS-CoV-2, too, mutates? “I suppose anything is possible, but to date this has not been observed. All the SARS-CoV-2 sequenced to date share the same core fusion peptide sequence exactly, and every sequenced coronavirus has an identical 6 amino acid fusion peptide core,” Zeichner said.
PEDV and SARS-CoV-2 are related, but distantly. “Yet, even these very distantly related coronaviruses share the same 13 amino acid fusion peptide core sequence,” Zeichner said.
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