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expert reaction to press release discussing early data from a phase 1 study (CORAL-BOOST) of a T cell-enhanced self-amplifying mRNA (samRNA) COVID-19 vaccine candidate (after two doses of AstraZeneca)

Press releases from the University of Manchester and Gritstone bio announce positive phase 1 clinical data from the first cohort their CORAL-BOOST study.


Prof Charles Bangham, Professor of Immunology, and Co-Director of the Institute of Infection, Imperial College London, said:

“This press release announces the outline results of a Phase 1 clinical trial of a second-generation vaccine against the COVID-19 virus, SARS-CoV-2.  Although the details of the construction of the vaccine are not yet made public, and the full data from this trial are not presented, the preliminary results nevertheless look very promising.  The vaccine was tested on small numbers of healthy adults (≥60 years old) who had previously received two doses of the Oxford/AstraZeneca vaccine, so it tests the safety of the vaccine and its ability to boost the immune response; future trials will be needed to test how efficiently it generates a primary response.

“There are two main differences from most of the widely distributed COVID vaccines that are now in use.  First, the vaccine generates an immune response not only to the spike protein of SARS-CoV-2, but also some of the other proteins of the virus.  This is important, because the other proteins differ much less between the variants of SARS-CoV-2 than the spike protein, so we would expect a better degree of cross-protection against different variants.  These proteins are well recognized by cytotoxic (‘killer’) T cells, and since the T cell response plays a critical part in protection, especially in clearing the virus from the body, the immunity produced by the vaccine should give good cross-protection against the virus variants.  The spike protein is also targeted by these killer T cells, and again the T cells recognize different variants better than the neutralizing antibody does – although the vaccine also elicited good levels of neutralizing antibodies.

“Second, the new vaccine is based on self-amplifying RNA (samRNA).  This amplifies itself to make large amounts of mRNA, reproducing the mRNA found in the Pfizer and Moderna vaccines.  Because it amplifies itself, only a small dose is necessary – this should make it possible to vaccinate many more people with the same amount of the vaccine.

“We look forward to seeing the full results of this promising trial, and the potential future trials in individuals who have neither had a previous COVID-19 infection nor received another COVID vaccine.”


Dr Peter English, Retired Consultant in Communicable Disease Control, Former Editor of Vaccines in Practice, past Chair of the BMA Public Health Medicine Committee, said:

“It is always difficult to comment on press releases such as this one, in the absence of more data.

“I have been aware that work has been in progress to develop better vaccines.  The ones we have, have been astonishingly effective – far more effective than we would have dared hope 15 months ago.

“But we also knew, when we realised that Covid-19 was caused by a coronavirus, that the virus could be expected to mutate and change.  This has, of course, been confirmed many times.  In particular, the spike protein – the target for all the original vaccines – changes. 

Various approaches are possible to stop the virus from being able to avoid immune the immune system, as the virus’ spike protein evolves to be different to the original virus’ version (and thereby, to avoid the antibodies produced against the original protein).

“One approach is to use platforms such as mRNA and vector platforms, that can rapidly be updated, to produce vaccines that are updated with new versions of the spike protein, based on circulating viruses.  This is similar to the approach taken with the annual influenza vaccination programme.

“Another approach is to stimulate antibodies to a range of different viral antigens – not just the spike antigen, but also to other parts of the virus that might be expected to mutate more slowly.  Even if they don’t mutate more slowly, if a virus targets several different parts of the virus, the chance that they will all mutate in a given period of time are much lower than that any one of the target areas will mutate to evade the antibodies.

“This is the approach taken with this trial vaccine: “[the trial vaccine] delivers antigens from both spike and non-spike proteins”.

“The manufacturer’s claim that this vaccine is designed to induce, in particular, a strong T-cell response, not just an antibody response; and a “broad” response that is likely to recognise and protect against, not just the precise antigen in the vaccine (and the virus); but also to similar antigens, meaning that they should still provide some protection against similar (but mutated) versions of the antigens.

“By incorporating parts of the virus that are common to other coronaviruses – such as the viruses that cause MERS, SARS, and some of the common cold viruses – it may, in time, be possible to develop a “pan-coronavirus vaccine”, that will prevent infection (or at least, severe disease) from any coronavirus.  The press release does not claim that this trial vaccine is such a vaccine; but they do say that it “may offer more robust clinical protection against current and future SARS-CoV-2 variants and be a first step toward developing a pan-coronavirus vaccine.”

“Self-amplifying mRNA (samRNA) vaccines work in a very similar way to the mRNA vaccines we have become used to.  The difference is that with the currently-used vaccines, the mRNA delivered into the body does not increase.  With samRNA vaccines, by contrast, the body makes more copies of the mRNA before transcribing the proteins it codes for, so a smaller dose packs a bigger antigenic punch1,2.

“The results reported are from a very small, early study.  It appears to be reporting results from only the first 10 individuals studied.  The trial vaccine was given at least 22 weeks after two doses of the AstraZeneca vaccine.  It induced (according to the press release):

  • “New CD8+ T cell responses across a wide set of non-spike epitopes, including many validated T cell targets in convalescent individuals, demonstrating the potential for variant-proof immunity
  • “A boost to pre-existing T cell responses to Spike epitopes (assessed by ELISpot) believed to be additive to antibody-based clinical protection conferred by Spike-dedicated vaccines Broad and potent neutralizing antibodies against SARS-CoV-2 Spike protein, at levels consistent with published data from higher doses of first-generation mRNA vaccines in a similar clinical context”

“In other words, it was effective at boosting antibody immunity to the spike protein, and, as hoped, it boosted T cell responses to the spike protein.  In addition, it induced cellular immunity to “a wide set of non-spike epitopes” – to other parts of the virus.

“This is, of course, a very small, preliminary trial.  It used only samples from people who had been vaccinated to look at the antibody and cellular immune responses to the vaccine: it does not use real-world data on the likelihood that they would be infected and infectious, or ill, following exposure to the virus.  The results have not been peer-reviewed.

“There are many hurdles before such a vaccine could be introduced for widespread use. 

However, this is very encouraging.  With new variants – like Omicron and B.1.640.2 – constantly evolving, vaccines that can more effectively prevent illness caused by variants of the virus may well have a place in our future armoury3.  Whether this particular vaccine will be such a vaccine – or will make it to market, be approved by regulators, and be widely used – will not become clear for some time.  But it may be; and if it doesn’t other novel vaccines with similar benefits may well take on this role.”

  1. Spencer AJ, McKay PF, Belij-Rammerstorfer S, Ulaszewska M, Bissett CD, Hu K, et al. Heterologous vaccination regimens with self-amplifying RNA and adenoviral COVID vaccines induce robust immune responses in mice. Nature Communications 2021;12(1):2893  PMID: 34001897. (
  1. Bloom K, van den Berg F, Arbuthnot P. Self-amplifying RNA vaccines for infectious diseases. Gene Therapy 2021;28(3):117-129. (
  1. Colson P, Delerce J, Burel E, Dahan J, Jouffret A, Fenollar F, et al. Emergence in Southern France of a new SARS-CoV-2 variant of probably Cameroonian origin harbouring both substitutions N501Y and E484K in the spike protein. medRxiv 2021:2021.12.24.21268174. (



University of Manchester press release title: ‘Early data for multivariant COVID-19 vaccine booster shows promise’.

Gritstone bio press release:

There is no preprint or paper and this work is not peer-reviewed.



All our previous output on this subject can be seen at this weblink:



Declared interests

Dr Peter English: “Dr English is on the editorial board of Vaccines Today: an unpaid, voluntary, position.  While he is also a member of the BMA’s Public Health Medicine Committee (and its chair until Oct 2020), this comment is made in a personal capacity.  Dr English sometimes receives honoraria for acting as a consultant to various vaccine manufacturers, most recently to Seqirus.”

None others received.



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