An Oxfordshire-based company will soon start clinical trials of a second-generation vaccine against Covid-19, an easy-to-administer skin patch that uses T-cells to kill infected cells and could offer longer-lasting immunity than current vaccines.
Emergex was set up in Abingdon in 2016 to develop T-cell vaccines, the brainchild of Prof Thomas Rademacher, the firm’s chief executive and professor emeritus of molecular medicine at the University College London medical school.
The vaccines prime T-cells to remove infected cells from the body quickly after infection, thus preventing viral replication and disease. While the antibodies produced by the current Covid vaccines stick to the virus and stop it infecting cells, T-cells find and destroy infected cells. Those other vaccines, such as the Pfizer/BioNTech and the AstraZeneca/Oxford University jabs, also produce a T-cell response, but to a lesser extent.
Emergex has received the green light from the Swiss drugs regulator to conduct initial human trials in Lausanne, involving 26 people who will receive a high and a low dose of its experimental Covid-19 vaccine, starting on 3 January. Interim results from the trial are expected in June.
Robin Cohen, the firm’s chief commercial officer, said: “This is the first time a regulator has approved a Covid vaccine to go into clinical trials whose sole purpose is to generate a targeted T-cell response in the absence of an antibody response and those T-cells look for infected cells and kills them.”
Using the analogy of an asteroid hitting a planet, he explained: “The virus is the asteroid: it fires into the planet and a viral code, a signature for that virus, is rapidly displayed all over the surface. These signatures are read by T-cells as foreign, and the T-cells kill the cell before it can produce new live viruses.”
Current Covid-19 vaccines mainly elicit an antibody response that wanes over time, which means people need booster shots to maintain protection against the virus. The Emergex vaccine works differently, by killing infected cells quickly. This means it could offer longer-lasting immunity – possibly for decades – and could also be better at fighting virus mutations, said Cohen.
A study published in Nature last week showed that some people experience “abortive infection” in which the virus enters the body but is cleared by the immune system’s T-cells at the earliest stage. Scientists said the discovery could pave the way for a new generation of vaccines targeting the T-cell response, which could produce much longer lasting immunity.
Danny Altmann, a professor of immunology at Imperial College London, said he doubted that a T-cell vaccine “could do the job on its own” but it could play a complementary role, in a mix-and-match approach where different vaccines are given for the first, second and third doses.
He said mRNA vaccines such as the Pfizer/BioNTech shot work so well because they produce a strong neutralising antibody response. The Pfizer vaccine has been shown to be more effective against Covid than the AstraZeneca/Oxford jab, which elicits a stronger T-cell response.
But a T-cell vaccine could be used to complement other jabs, he said, as T-cell vaccines might be more impervious to virus mutations. “Antibodies are very sensitive to mutations while T-cells can see many other parts of the virus. Maybe that’s a selling point for T-cell vaccines.”
He noted that the idea of T-cell vaccines was not new – for example, Prof Sarah Gilbert, the University of Oxford professor who developed the AZ/Oxford jab, has been working on them for influenza for more than a decade.
Cohen said the tricky part was working out the delivery mechanism for the Emergex vaccine to the immune system. Rademacher and his team settled on tiny gold particles coated in peptides (bits of proteins) designed to generate the T-cell response in the body.
The vaccine will eventually be administered as a skin patch the size of a thumbnail bristling with micro-needles that release the shot within seconds. It can last for up to three months at room temperature, unlike other jabs that need to be stored in the freezer or fridge.
The trial will be conducted by Prof Blaise Genton from the centre for primary care and public health at the University of Lausanne, Switzerland. He said: “This exciting new scientific approach to developing a vaccine against Sars-CoV-2 addresses the need to generate a T-cell response to elicit long-term immunity.”
However, the Emergex shot will not be available until 2025 at the earliest, the usual timeframe for vaccine development. Last year Covid vaccines were developed within months as the regulatory process was speeded up, but the emergency has passed, said Cohen.
Emergex is testing another T-cell vaccine against dengue fever on humans in a separate Swiss trial, with initial results due in January. Half the world is at risk from dengue fever, according to the World Health Organization, and there is no specific treatment or vaccine for it. The firm also wants to deploy its T-cell vaccines against influenza, Zika, Ebola and and other infections.
Dr Andrew Freedman, a reader in infectious diseases at Cardiff University school of medicine, said last week: “A vaccine that primes T-cell immunity against different viral protein targets that are shared between many different coronaviruses would complement our spike vaccines that induce neutralising antibodies.”