LONDON – A large scale U.K. study looking at the impact of COVID-19 vaccinations on antibody responses and new infections in 373,402 people in the general population has shown a single dose of vaccine cut infections by 65%.

Symptomatic infections fell by 74% and infections with no reported symptoms by 57%, 21 days after receiving the first dose of either Astrazeneca plc’s or Pfizer Inc./Biontech SE’s vaccine.

At 21 days after the second dose of Pfizer/Biontech vaccine symptomatic infections fell by 90% and asymptomatic ones by 70%. That is similar to the effect seen in people who had previously been infected with COVID-19 naturally.

Rollout of the Astrazeneca vaccine began later in the U.K. and there are no data as yet on what happens after a second dose of this product.

Both vaccines were effective against the B.1.1.7 variant of the virus, first detected in the U.K. in December 2020, and now accounting for most infections across Europe and the U.S.

That is significant because B.1.1.7 was not in circulation when the clinical trials took place and there was some in vitro data indicating the variant might reduce effectiveness of the two vaccines.

These findings on vaccine efficacy are based on 1.61 million PCR tests run on nose and throat swabs taken between Dec. 1 and April 3, 2021. Participants in randomly selected households across the U.K. were visited and swabbed at home.

The national vaccination programme began on Dec. 8.

Scale apart, “The main advantage of this study is that the [PCR] tests are independent of vaccination status or symptoms,” said Koen Pouwels, senior researcher at Oxford University’s department of population health.

The fact there were smaller reductions in asymptomatic infections than in infections with symptoms, highlights the potential for people to catch COVID-19 post-vaccination. That points to an ongoing risk of transmission from vaccinated individuals, “even if this is at a lower rate,” Pouwels told a press briefing. “This emphasizes the need for everyone to continue to follow guidelines to reduce transmission risk,” he said.

Without large community surveys, “It is impossible to estimate the impact of vaccination on infections without symptoms. These have the potential to keep the epidemic going, particularly if people who have been vaccinated mistakenly think they cannot catch COVID-19,” said Sarah Walker, professor of medical statistics and epidemiology at Oxford University, who is chief investigator for the U.K. COVID-19 infection survey.

Of course, the key question is whether vaccines alone can control the pandemic. In the U.K. the number of new infections has come down from 60,000 per day at the peak of the second wave in mid-January, to 2,729 on April 21. However, for most of that time strict national social distancing and other control measures were in place.

Walker said the findings make her “cautiously optimistic” that vaccines can control what she said is now an endemic, rather than a pandemic infection. “Long-term, lockdown is not a viable solution. Vaccination is the only way you can control long term,” she said. However, she also cautioned that as the examples of India, Canada and Brazil illustrate, “the virus can deal us a curve ball.”

Immune responses

The infection survey has been randomly testing individuals for infection with SARS-CoV-2 since April 2020. It has now processed 3.9 million swabs and 300,000 blood tests. Blood testing is currently being ramped up to allow more detailed investigations of immune responses against the virus and the vaccine.

Based on the clinical trial data, vaccines manufacturers have claimed their products are 100% effective at preventing serious disease and deaths. However, the researchers said it is not possible to confirm this from their study.

It is possible to tease out the effect on the immune system of vaccination versus natural infection by testing for antibodies against the spike protein of the virus – which are elicited by both natural infections and vaccines – and for antibodies against the nucleocapsid, which occur only after natural infection.

Antibodies against the spike protein were seen in 45,965 participants post vaccination. “The main message is we saw strong antibody responses [after vaccination] in 95% of individuals,” said David Eyre, associate professor at the Big Data Institute at Oxford University.

Although the strongest responses were in younger people, all age groups mounted an immune response, which was maintained to the 10-week cutoff of this tranche of data. Antibody levels rose from day 1 to day 14 and then plateaued.

Antibodies reached a peak sooner after vaccination with Pfizer/Biontech than with Astrazeneca’s product, but then fell off slightly so that the antibody titres for both vaccines were the same at seven weeks post vaccination.

Eyre said that is good “in the context of the 12-week interval” between first and second doses that the U.K. opted for in order to maximize the public health benefits of limited supplies of vaccine.

The study will continue to track the immune response to vaccination, to see how long antibodies persist, and if they are effective against variants of concern.

However, Walker noted, infection levels in the U.K. are now so low that the power of the study to detect effects is reduced. It is hoped there will be sufficient evidence to indicate when booster doses of vaccine are needed and when/if reformulations are required to protect against variants of concern.