Can we rely on there being a vaccine for SARS-COV2?

Of the 200 vaccines that are being worked on, results came in from phase I and II trials of four promising vaccine candidates, and detail how people respond to the jabs. Because the trials were focused on safety and dosing, the data cannot say whether the vaccines will actually prevent Covid-19 disease or infection — large-scale efficacy trials are needed for this.

But they suggest that the candidate vaccines are broadly safe, and offer the first hints that vaccines can summon immune responses similar to those of people who have been infected with the virus. Some of the vaccines, like the Oxford collaboration one, do not use an inert placebo to compare against for safety, but another vaccine such as the meningococcal A vaccine. This is a ‘control’, not a ‘placebo’, and it is important to recognise that a comparison is being made with a substance that carries its own side effects, and is not an inert placebo.

Researchers don’t know the precise nature of the immune responses that protect against COVID-19 — and there are likely to be multiple ways to fend off infection. Furthermore, measurements of immune markers made in one lab are difficult to compare with those performed by another team, say scientists.

Viral vectors

All four vaccine-makers said that their vaccines elicited some kind of immune response, broadly similar to the responses seen in people who have recovered from COVID-19. Trial participants experienced side effects commonly seen with other vaccines, such as muscle pain, fevers and headaches, but few developed serious reactions to the vaccines.

Two teams — one at the University of Oxford, UK, in collaboration with pharmaceutical company AstraZeneca, and one made up of researchers at CanSino Biologics in Tianjin, China — that are developing ‘viral vector’ vaccines’.

Oxford’s vaccine harnesses a virus that causes colds in chimpanzees, but that has been genetically modified so that it can’t grow in humans, and so that it expresses the ‘spike’ protein that the coronavirus uses to infect human cells. CanSino’s vaccine uses a similarly modified human virus.

A third group, BioNTech in Mainz, Germany, is developing an RNA-based vaccine with drug company Pfizer. On 20 July, the team released detailed immune data from people who had received a vaccine containing RNA instructions for the ‘receptor binding domain’ portion of the spike protein. This followed long-awaited clinical-trial results published on 14 July by Moderna, a biotech company in Cambridge, Massachusetts, that has developed a competing RNA vaccine made of the entire spike protein, in collaboration with the US National Institute of Allergy and Infectious Diseases (NIAID) in Bethesda, Maryland.

Vaccines expose the immune system to components of a virus — the coronavirus spike protein, in the case of nearly all COVID-19 vaccines — in the hope of teaching it how to react against a real infection in the future. The trials looked at two broad types of immune response: production of antibody molecules that can recognize and, in some cases, inactivate viral particles; and production of T cells that can kill infected cells and promote other immune responses, including antibody production.

So far, most focus has been on ‘neutralizing antibodies’ circulating in the blood, which can render viral particles non-infectious. All of these vaccines are inducing some antibodies that neutralise, which is better than no neutralising. says Ahmed. The crucial issues are does this induction of neutralising antibodies actually confer protection from the disease, and second, how long would any protection last for? It seems that natural (i.e. non vaccine induced) antibodies to SARS COV-2 are only effective for three months or so.

T-cells

T-cell responses have received less attention from vaccine developers. That’s partly because they are more difficult to measure, especially as the number of trial participants pushes into the thousands. But emerging data suggest that T cells might have an important role in controlling the coronavirus.

Vaccine trials detected varying degrees of T-cell responses in participants. One team detected spike-recognizing CD4 T cells, which support antibody production, in all ten of the recovered people they examined. Seventy per cent also had spike-recognizing CD8 T cells, which kill virus-infected cells.

The nature of the immune response that protects — or fails to protect — against COVID-19 will become clearer when efficacy trials deliver their first results.