Could DNA-based COVID-19 vaccine offer variant-busting booster shot?

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Pic:getty/novodka (Getty Images/iStockphoto)

With Scancell taking its DNA-based COVID-19 vaccine tech into clinical trials this year, it is already focusing its attention on the tech’s potential to be used as a needle-free booster shot to address Variants of Concern.

The vaccine is due to enter a Phase 1 trial in South Africa in H2, 2021. Once safety data has been received, a trial in the UK will administer the vaccine as a booster shot to people already fully vaccinated with two authorized COVID-19 vaccines.

With the DNA tech designed to accommodate multiple antigens – unlike current mRNA vaccines which incorporate a single antigen – this could be used to protect against Variants of Concern.

Green light for South Africa trial

The COVIDITY programme, focused on the Company’s novel COVID-19 vaccine candidates SCOV1 and SCOV2, is a collaboration between Scancell and scientists in the UK's newly established Centre for Research on Global Virus Infections and the new Biodiscovery Institute at the University of Nottingham, and Nottingham Trent University.

The program last week received the green light from the South African Health Products Regulatory Authority (SAHPRA) to start a Phase 1 trial in the country in H2, 2021: which will cover unvaccinated individuals. 

The objectives will be to assess the safety and immunogenicity of the two vaccine candidates, SCOV1 and SCOV2, evaluating different vaccine doses delivered by two alterative injection routes using needle-free systems (the company declined to comment further on the nature of the needle-free systems).

In addition to evaluating the virus-neutralising antibodies, the company will also analyse the T cell responses to the N protein, which will provide additional information and data on the potential utility of both SCOV1 and SCOV2 against future SARS-CoV-2 variants.

Once safety data has been gathered from the first trial, Scancell will seek approval from the UK's Medicines & Healthcare products Regulatory Agency (MHRA) to initiate a UK extension of the study in which COVIDITY will be given to healthy volunteers who have already received two doses of an approved vaccine.

The immune responses from this part of the COVIDITY study will allow Scancell to assess the ability of SCOV2 to boost the immune response against current and potential future strains of COVID-19 in prevaccinated individuals.

Build on Scancell's cancer vaccine concept

SCOV1 and SCOV2, targeting the original and variant SARS-CoV-2 viruses, respectively, are based on a modification of Scancell's ImmunoBody DNA vaccine technology and have a dual mechanism of action to induce high avidity T-cell immune responses against both the N and S viral antigens.

Targeting the receptor-binding domain (RBD) of the S antigen, the vaccines also elicit high titre virus-neutralising antibodies that cross-react against a range of Variants of Concern (VoC), including the new Delta variant.

“The development of a variant vaccine that also incorporates the N antigen as well as a variant RBD to broaden cross-reactivity has a potential advantage over currently approved vaccines,” a Scancell spokesperson told this publication.

“The inclusion of a single antigen in all of the currently authorised vaccines leaves open the possibility of escape from vaccine protection and the emergence of new viral variants.

“Nucleic acid-based vaccines can be designed very quickly, which is why these were among the first COVID-19 vaccines to enter clinical trials. Both DNA and mRNA vaccines induce humoral as well as cellular immunity and are very safe as they are not associated with replicating microorganisms.

“However, mRNA vaccines can only incorporate a single antigen – the inclusion of two antigens would require the development of a second, separate mRNA vaccine. DNA vaccines such as COVIDITY can accommodate multiple antigens in the same vaccine.”

Compared to viral vector vaccines, Scancell notes the hesitancy around these over blood clot fears in these types; while noting that anti-vector immunity could emerge as a problem. “Multiple boosting for these virally-vectored vaccines will be limited by progressive boosting of anti-vector immunity and new variant adenovirus-based vaccines may not be feasible due to pre-existing vector immunity that is likely to abrogate responses against any new insertion.”

DNA vaccines could also provide large-scale, low cost manufacture, with long-term stability and no need for ultra-cold storage, the company adds.

While there are already a number of authorized vaccines ramping up supply, Scancell believes a number of different vaccines will be required.

“Ultimately, it is likely that a repertoire of COVID-19 vaccines will be required to offer widespread protection. Different vaccine formulations will ensure vaccination is safe and effective for all members of society, including infants, the elderly and people with weakened immune systems. The requirement for billions of vaccine doses worldwide also suggests that there will need to be multiple vaccines in circulation with different manufacturing processes to minimise shortages in raw materials.”