Between Oct. 1 – Jan. 14, the researchers at Oxford University who co-developed the vaccine, used swabs taken from volunteers with both symptomatic and asymptomatic infections to work out which variant of the virus had infected them after receiving either the vaccine or control.
They found the level of protection against symptomatic infection was similar for both variants. That is despite lower neutralizing antibody titers in people infected with B.1.1.7, compared to those infected with the original variant against which the vaccine was designed.
“The most important finding is that here in the U.K. we have seen very similar efficacy of the vaccine against B.1.1.7, compared to the original virus,” said Andrew Pollard, professor of pediatric infection and immunity at Oxford University, principal investigator on the trial.
The study, published in a preprint, also indicates that people immunized with the Astrazeneca vaccine who subsequently contracted COVID-19, had a reduction in duration of infection and a lower viral load, compared to controls (who received meningitis A vaccine). That may translate into reduced transmission of disease, Pollard said.
A total of 325 viral samples were sequenced, from 256 participants who contracted the infection.
This is positive news. B.1.1.7, first sequenced from viral samples taken in Kent, southeast England, in December, has been shown to have a transmission advantage over previous variants of the virus. It is now the dominant lineage in the U.K. and other countries.
The results are not unequivocal, given the lower titers of anti-spike protein IgG neutralizing antibodies in participants infected with B.1.1.7.
“There is a slight shift in efficacy from a statistical point of view,” Pollard told a press briefing. “But the confidence intervals overlap.” The data are in “a similar ballpark” to those seen in previous studies and close to each other. “[Efficacy] is still in the high 70% or 80%.” Pollard said.
“We know from other vaccines it is not going to be a surprise to see reduced efficacy,” said Mene Pangalos, executive vice president of biopharmaceuticals R&D at Astrazeneca. Reduced efficacy against variants also has been seen with Johnson & Johnson’s and Novavax Inc.’s COVID-19 vaccines.
“You don’t need particularly high levels of neutralizing antibodies to protect against moderate and severe disease,” Pangalos noted. “The numbers we should care about are 100% effectiveness against severe disease and hospitalizations,” he said.
A similar piece of research is ongoing in South Africa to see if Astrazeneca’s vaccine remains effective against the 501.V2 variant, considered to be of greater concern because it carries E484K, a mutation which initial studies have shown weakens the immune response and the longevity of neutralizing antibodies.
The South African trial has fewer participants, meaning it is taking longer for data to accumulate, but Pollard said results are expected soon.
The phase III U.S. trial of the Astrazeneca vaccine, which has 30,000 participants, is expected to read out in the next few weeks. The initial data will not compare the effectiveness against different variants, but Pangalos said that information is expected over time.
E484K has now been detected in B.1.1.7 samples in the U.K. However, that mutation did not occur in any of the viral genomes sequenced from the 323 swabs in the Oxford study.
The study measured only IgG antibodies against the SARS-CoV-2 spike protein, and Pollard said it is not clear if efficacy of the Astrazeneca vaccine was maintained despite a fall in levels of this antibody, because protection was coming from other antibodies or T cells.
It is fair to speculate that is the case, but said Pollard, “We don’t have the answer to this.”
This is the first published clinical data showing the Astrazeneca vaccine remains effective against B.1.1.7, despite the fact it was not designed against the variant.
It means it is not yet necessary to change the genetic payload; however, SARS-CoV-2 is clearly making changes in its spike protein to evade the human immune response.
Sarah Gilbert, professor of vaccinology at Oxford University and co-developer of the Astrazeneca vaccine, said the Oxford Vaccines group is working with Astrazeneca on strain changes should one become necessary. “We are using the platform technology to slot in new gene sequences, to quickly develop vaccines against variants. Other developers are doing a similar thing.
“It is really no surprise we are seeing changes in the virus as it circulates through the human population,” said Gilbert. “Coronaviruses are less prone to mutation than influenza viruses, but we have always expected that, as the pandemic continues, new variants will begin to become dominant amongst the viruses that are circulating and that eventually a new version of the vaccine, with an updated spike protein, would be required to maintain vaccine efficacy at the highest level possible.”
The exercise is the same as last year, when vaccines developers responded as soon as the gene sequence of SARS-CoV-2 became available. The difference now is that there is experience on which to build and the regulatory process will be swifter, Gilbert noted.
“We will be talking to regulators about approval; it won’t be as onerous,” she said.