Early tests showed the jab, developed by US biotechnology company Novavax, leads to high levels of virus-fighting antibodies being produced.
The trial on 10,000 people will now see if the vaccine can prevent people getting ill.
The UK government has already ordered 60 million doses in case it proves successful.
A vaccine that can protect people from Covid-19 is still widely seen as the main exit strategy from the restrictions on all our lives.
The Novavax jab is only the second to enter large scale trials in the UK; the other has been developed by the University of Oxford.
Some of the vaccines being developed for Covid-19 use either completely new or barely proven technologies.
Novavax are using traditional methods – proteins from the coronavirus that cannot replicate in the body and a chemical, called an adjuvant, to boost the immune response.
“It’s a technology that we are more familiar with,” Prof Paul Heath, who is leading the trial at St George’s University Hospitals NHS Foundation Trust, told the BBC.
He added: “This is an open field and we don’t know what will work, that is the truthful answer here,. And that’s the reason there are so many different vaccine candidates.”
Early trial data on 83 people, published in the New England Journal of Medicine, showed the vaccine appeared safe.
Blood samples from those injected showed the volunteers were producing antibodies that could neutralise the coronavirus and another part of the immune system, called T-cells, were also trained to fight the virus.
While this is a promising sign, it is not enough to prove the vaccine can either stop infection or prevent someone developing the severest form of the disease.
Ten thousand people will take part in the trial and at least a quarter of them will be over 65, the age-group most at risk of severe Covid-19.
Some of the volunteers will be picked from those who have signed up to take part in clinical trials run by the NHS.
Half will be given two doses of the vaccine, three weeks apart, and the rest will be given a dummy jab called a placebo.
However, it will take months – probably early 2021 – before we know if the vaccine is successful.
“This is a really exciting moment, this is only the second phase three efficacy trial in the UK,” Prof Heath told the BBC.
“This vaccine looks like an excellent candidate to be protective against Covid-19, but we need now to prove that.”
The vaccine will be manufactured in Stockton-on-Tees.
Kate Bingham, chairwoman of the government’s Vaccines Taskforce, said: “Finding a safe and effective vaccine that works for the majority of the UK population is the best way to tackle this devastating disease.
“Whilst social distancing, testing and other measures can help reduce the impact of coronavirus, the only long-term solution to beating it will be finding a vaccine.”