Frontier IP : TVG next-generation COVID-19 vaccine achieves significant milestone

29/11/2021

• Trial data show strong T cell responses to SARS-CoV-2, as well as the more divergent SARS-CoV-1, demonstrating potential for broad immunity against current and future variants of the causal agent of COVID-19
• Vaccination is not blunted by pre-existing immunity against the vaccine platform allowing for repeated use as a 'booster' after initial vaccination

The Vaccine Group ("TVG" or the "Company") today announces the results of pre-clinical trials in pigs for a SARS-CoV-2 vaccine candidate for use in humans based on its novel herpesvirus-based vaccine platform technology.

The results show that a strong T cell response is stimulated by a single immunisation, which is further boosted by a subsequent immunisation with the identical vaccine after a four-week interval. The trials were run in collaboration with The Pirbright Institute, England.

Laboratory analysis of immune responses to the vaccine confirmed T cell responses in all animals. Further analysis showed both SARS-CoV-2-specific gamma interferon producing CD4⁺ helper T cells and CD8⁺ cytotoxic T cells (CTLs) against SARS-CoV-2 were induced.

The vaccine has been developed to direct T cell immune responses against three SARS-CoV-2 proteins. The potential for such a T cell-focused vaccine approach has been highlighted following recent reports of substantial T cell-based immune memory in SARS-CoV-2 convalescent patients* and a correlation of immunological control with the prevalence of CTLs**.

CTLs are an important part of the body's defence system because they destroy cells infected by the virus. This means they remove infected cells swiftly, before the virus can replicate. Most vaccines either on the market or under development are aimed at attacking the virus directly once it has already replicated and been released from the infected cell by stimulating an antibody response against the spike protein on the surface of the virus. However, antibodies are more sensitive to evasion by virus mutation.

In vitro stimulation of lymphocytes isolated from peripheral blood samples after vaccination showed reactivity against peptides from both SARS-CoV-2, the causal agent of the COVID-19 pandemic, and also the SARS-CoV-1 virus isolated from the 2003 SARS outbreak.

These data underline the ability of this vaccine to stimulate broad coronavirus immune responses which would be expected to be beneficial in controlling infection with current circulating SARS-CoV-2 viruses (e.g., Delta) as well as future variants of the virus.

Pathogen targets of T cell-based immunity are known to vary less than antibody targets, therefore this result is in line with this vaccine strategy.

Following early discussions with the UK's MHRA, TVG is seeking immediate funding to move the vaccine candidate to a full Proof-of-Concept stage before Phase I trials in humans can be undertaken.

The vaccine candidate is based upon TVG's herpesvirus vector system, which allows for repeated reimmunization and booster doses to be used without decreasing efficacy.

"These very strong trial results show that a COVID-19 vaccine based on our novel herpesvirus platform could prove to be extremely effective in mitigating the long-term impact of the disease. We are clearly excited about the potential for the vaccine."

The Vaccine Group Chief Executive Officer Jeremy Salt

"Given the emerging data that strongly suggest an important role for cellular immunity in controlling SARS-CoV-2 infection, these are particularly promising results."

Simon Graham, Group Leader at The Pirbright Institute

"The first generation of COVID-19 vaccines have had a fantastic impact. However, COVID-19 is not going to disappear, so there is a need for a new generation of vaccines. There is a growing body of evidence to show that stimulating a T cell response confers longer-lasting immunity than other approaches and also offers the potential to provide protection against current and future variants of the disease

Frontier IP Chief Executive Officer Neil Crabb

* Le Bert,et al 2020 https://www.nature.com/articles/s41586-020-2550-z;

* Grifoni et al, 2020 https://www.cell.com/action/showPdf?pii=S0092-8674%2820%2930610-3

** Swadling, L., Diniz, M.O., Schmidt, N.M. et al. Pre-existing polymerase-specific T cells expand in abortive seronegative SARS-CoV-2. Nature (2021). https://doi.org/10.1038/s41586-021-04186-8

** Luo et al. 2020. https://pubmed.ncbi.nlm.nih.gov/32544099/