Babraham Institute study of Oxford University’s Covid-19 vaccine underscores importance of second dose

A study involving mice suggests the second dose of Oxford University and AstraZeneca’s Covid-19 vaccine will be particularly important to generate an effective immune response in older people.

Immunologists at the Babraham Institute studied the effect of age on the immune response to the vaccine.

Their findings agreed with vaccine trial data, published in The Lancet, that showed two doses are required for younger and older people to have a similar immune response.

Dr Michelle Linterman, a Babraham Institute group leader and lead on the research study, said: “As we get older, our immune system function declines and we become more vulnerable to infectious disease.

“The current pandemic has highlighted how much of a health imbalance this can cause. This work has allowed us to analyse the immune system response to the vaccine at cellular resolution and learn more about how age affects this.”

The first doses of the vaccine - known as ChAdOx1 nCoV-19 by the Oxford Vaccine Group that developed it - were administered at UK hospitals on Monday.

Those receiving it will wait up to 12 weeks for their second dose - rather than the minimum period of four - after the Joint Committee on Vaccination and Immunisation (JCVI) advised the government to prioritise giving people in at-risk groups their first shot, instead of providing both in as short a time as possible.

The government has stressed: “Everyone will still receive their second dose and this will be within 12 weeks of their first. The second dose completes the course and is important for longer-term protection.”

The Babraham study was published online in Med, a new journal from Cell Press, before this decision and prior to the regulatory approval of the vaccine.

But it underscores the importance of ensuring people receive their second dose.

Working with the research team of Teresa Lambe, who developed the vaccine at the University of Oxford’s Jenner Institute, scientists at the Institute used mice between three months - the mouse equivalent of the prime of life - and 22 months, which is the mouse equivalent of old age.

Although ageing in mice and humans happens on very different timescales, many of the biological changes in the immune systems with age are seen in both.

Previous research using mice has also demonstrated that strategies to boost immune responses in older mice are also effective in humans.

The Institute researchers found a single dose of the vaccine triggered an immune system response in older mice, but this was reduced when compared to the response in younger adult mice.

The scientist closely analysed different immune cell types that form the body’s overall ‘surveillance’ system and the cells that specifically identify and kill infected cells.

Providing the second booster dose a month later enhanced the immune response in older mice, overcoming the deficiency of the first response.

Dr Lambe, associate professor and Jenner investigator at the University of Oxford, said: “Stimulating the production of long-lived antibodies is key to securing longer-term immunity. While the aged mice initially showed a compromised ability to produce these, a booster dose of the vaccine improved this response.”

This study did not explore the different impact of the timing of the second dose. But clinical trials of the vaccine showed that the second dose was effective when administered at different timescales of between four and 12 weeks.

The government said its decision to delay the second dose of both the Oxford vaccine and the Pfizer/BioNTech vaccine approved earlier in December “will protect the greatest number of at risk people overall in the shortest possible time and will have the greatest impact on reducing mortality, severe disease and hospitalisations and in protecting the NHS and equivalent health services”.

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