COVID-19: Longer Delay for Second Oxford Vaccine Dose 'Improves Immune Response'

Peter Russell

June 28, 2021

Delaying a second dose of the AstraZeneca/Oxford COVID-19 vaccine for longer than current practise leads to an enhanced immune response, scientists from Oxford University have said.

A third dose of the ChAdOx1 nCoV-19 vaccine continues to boost antibodies against SARS-CoV-2, as well as increasing T-cell responses, according to results in a preprint study which has yet to be peer-reviewed.

Typical intervals between first and second doses around the world vary between 4 and 12 weeks. 

In a briefing to the Science Media Centre, Dr Teresa Lambe PhD, lead senior author, said they had been able to show that with "a prolonged interval of 15 to 25 weeks, and even as long as 44 to 45 weeks between dose one and dose two, you get a very strong antibody induction with these really long intervals".

Dr Teresa Lambe/SMC

Dr Lambe, an associate professor at the University of Oxford's Jenner Institute, also reported an additional finding that in individuals fully vaccinated with the AstraZeneca/Oxford vaccine, "when we gave them a third dose after about 30 weeks, we were able to augment the immunity – the antibody levels – and we were able to push them up to a level that we saw at the peak of the response after the second dose".

The study involved volunteers aged 18 to 55 who were enrolled in a phase 1/2 or phase 2/3 clinical trial of ChAdOx1 nCoV-19 and had received either a single dose or two doses of the vaccine.

Thirty participants received a late second dose of ChAdOx1 nCoV-19, a median of 44 weeks after the first dose. Antibody titres were found to be higher in those who received a second dose at 44 to 46 weeks after a first dose compared with those where the dosing interval was 8 to 12 or 15 to 25 weeks.

Booster Doses

Of the 90 participants who received a third dose, antibody titres were significantly higher when compared with the response 28 days after a second dose.

Prof Sir Andrew Pollard/SMC

Prof Sir Andrew Pollard, director of the Oxford Vaccine Group, said it was too early to say whether booster shots would be required in the autumn because there was currently a lack of real-world data about how long immunity lasted following vaccination. However, "it is something where we need to keep looking at the data and make decisions as the months go by, about whether that protection that we have is lost," he told the briefing.

"We would expect to see immunity start to wane over time because that does happen. It won't go back down to zero, but the levels you can measure in the blood will become lower over time."

However, Prof Pollard added: "But our immune systems are a bit too clever for us to just look at those numbers, which is what most people are doing at the moment. The immune system remembers that we've been vaccinated, so even if we meet the virus some months later, the immune system will remember and it will kick in and make stronger immune responses again, and hopefully that will protect most people from severe disease."

There was also uncertainty about the effects of variants on current vaccines, although Prof Pollard said: "We've seen very high levels of protection here in the UK against the Alpha variant and the Delta variant, even though the vaccines were designed from the original strain of the virus, so these are already mutants that are being dealt with very effectively by vaccines, keeping people out of hospital."

Trials Begin of 'Variant' Oxford Vaccine

The University of Oxford and AstraZeneca announced yesterday the start of human trials for a new vaccine tweaked for effectiveness against the Beta variant first identified in South Africa.

The phase 2/3 trial of the vaccine, known as AZD2816, will involve around 2250 volunteers from the UK, South Africa, Brazil, and Poland.

The study aims to assess the immune response to the Beta variant with the new vaccine, which is for use potentially in combination with the current AstraZeneca/Oxford vaccine.

Initial data from the trial is expected later this year, the University of Oxford said.

Tolerability and immunogenicity after a late second dose or a third dose of ChAdOx1 nCoV-19 (AZD1222)’ by Amy Flaxman et al. (preprint)


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