The first human trials of DNA vaccines designed to produce live viruses in people鈥檚 bodies could start next year. A US company called Medigen has told New 杏吧原创 it is seeking approval for such trials.
The aim is to combine the potential advantages of DNA vaccines, including rapid manufacturing and easy storage, with the greater efficacy of vaccines that consist of live weakened viruses.
鈥淪o instead of giving live virus, we would give a piece of DNA and the body will make the vaccine,鈥� says at Medigen, based in Frederick, Maryland. 鈥淭hat鈥檚 the approach and it鈥檚 working.鈥�
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Medigen has tested two potential vaccines of this kind in mice so far, one for chikungunya and the other for yellow fever. The DNA vaccines protected the animals when they were later exposed to infection-causing viruses.
The company hopes trials in people will begin next year. 鈥淲e are in discussion with the FDA [US Food and Drug Administration],鈥� says Pushko. 鈥淎s soon as we get the FDA approval, we can start testing in a phase 1 clinical trial.鈥�
All early vaccines consisted of live viruses that caused milder symptoms than the conditions they were intended to prevent. Many vaccines today still consist of live weakened viruses, including the chickenpox and nasal flu vaccines.
The main advantage of live vaccines is that they typically produce strong and long-lasting protection after a single dose. The disadvantage is that in people with weakened immune systems, there is a risk of dangerous infections. It is also possible for weakened viruses to mutate and revert to the dangerous form, which happens with the live polio vaccine,聽albeit rarely.
Because of the safety issues, many modern vaccines consist of 鈥渄ead鈥� viruses that can鈥檛 replicate, or of viral proteins rather than an entire virus, such as the human papillomavirus (HPV) and hepatitis B vaccines. However, these vaccines typically require repeated doses to produce a strong enough response.
With any vaccine that consists of entire viruses or viral proteins, manufacturing requires highly trained personnel and specialised facilities tailored to each vaccine. This means ramping up production in the event of a pandemic is difficult, hence the interest in RNA and DNA vaccines.
DNA is found mainly in the nucleus of cells and stores the recipes for making proteins. Temporary copies of DNA recipes are made from RNA, and these carry the recipes from the nucleus to protein-making factories in the main cell body. These copies are called messenger RNAs or mRNAs.
The idea with both mRNA and DNA vaccines is to get our cells to do the hard part of manufacturing the viruses or viral proteins. RNA and DNA are relatively cheap and easy to produce, and the same manufacturing processes can be used to make different vaccines.
One potential advantage of DNA vaccines over mRNA ones is that the molecule is more stable. DNA vaccines can be kept in a fridge or even at room temperature, rather than needing to be kept frozen like most mRNA vaccines, says Pushko.
The problem is delivery. Whereas an mRNA vaccine only needs to get past the cell membrane, a DNA vaccine has to get into the nucleus of the cell. This requires special methods such as injection via microneedles, and many candidate DNA vaccines coding for viral proteins have failed to produce a strong enough immune response in trials.
As of yet, no DNA vaccine has received full approval, though in 2021 India granted emergency authorisation to coding for two viral proteins.
DNA vaccines coding for live viruses help solve the delivery problem because once a few viruses are made, they start replicating themselves, says Pushko. So people get an effective dose even if relatively few DNA molecules reach the nuclei of cells.
to the wild form, Medigen has also deleted some viral genes and rearranged others, says Pushko. It is also developing similar vaccines for other emerging infections of concern, including Japanese encephalitis and Lassa fever.
鈥淚 like the idea of this,鈥� says at the University of British Columbia in Canada. 鈥淚 anticipate it would have the production, stability and storage ease of [DNA] but the potency of a live attenuated virus. Obviously, the main concern is the safety of a live attenuated virus, especially in an immunocompromised patient.鈥�
Pushko thinks that live DNA vaccines could play a crucial role in the event of another pandemic. Being able to quickly produce a vaccine that provides effective protection after just one dose could save many lives if a virus with a high death rate began spreading, says Pushko.
