Research on the ChAdOx1 nCoV-19, also known as the Oxford-AstraZeneca vaccine, indicates that a long interval between first and second doses does not compromise the immune response after a late second dose.

Additionally, a third dose of the vaccine continues to boost antibodies against SARS-CoV-2. The results were released in a preprint today.

Delayed second dose

The researchers found that longer dose intervals between the first and second dose led to higher antibody levels. They reported that for those who had eight to 12 weeks between dose one and two (median age 39), the median antibody level 28 days after the second dose was 923 tIgG EU. For those who had a 15 to 25 week interval (median age 36), it was 1860 tIgG EU and for the 44 to 45 week interval (median age 32) it was 3738 tIgG EU.

Six months after the second dose, antibody levels remained significantly higher in the group who had a 15 to 25 week interval between doses compared with the eight to 12 week interval group—median 1240 tIgG EU and 278 tIgG EU respectively. The data are not yet available for the 44 to 45 week interval.

The team added that the IgG binding titres to the four variants tested (D614G, alpha, beta, and delta) were “significantly greater” after the second dose than before the second dose.

Booster dose

For the booster (third) dose, 75 participants who had their first two doses with an interval of eight to 16 weeks were assessed. The preprint reported that antibody levels 28 days after the third dose were significantly higher than 28 days after the second dose—3746 tIgG EU and 1792 respectively.

The team also found that binding antibody titres to the beta variant “increased significantly” after the third dose, while neutralising antibody titres following the booster were higher than those after the second dose against alpha, beta, and delta variants.

COVID-19 vaccine supply shortages are causing concerns in some countries about compromised immunity as the interval between first and second dose extends due to limited vaccine availability. When examining the effects of a delay of up to 45 weeks between first and second doses in study participants, results demonstrated that antibody levels were increased after a delayed second dose. Additionally, a longer delay between first and second doses may be beneficial, resulting in an increased antibody titre and enhanced immune response after the second dose.

Professor Sir Andrew Pollard, Professor of Paediatric Infection and Immunity and Lead Investigator of the Oxford University trial of the vaccine, says, ‘This should come as reassuring news to countries with lower supplies of the vaccine, who may be concerned about delays in providing second doses to their populations. There is an excellent response to a second dose, even after a 10 month delay from the first.’

Conversely, some countries are considering administering a third ‘booster’ dose in the future. Studying the impact of a third vaccine dose, the researchers found that antibody titres increased significantly with a third dose. T-cell response and the immune response against variants were also boosted.

‘It is not known if booster jabs will be needed due to waning immunity or to augment immunity against variants of concern,’ says Associate Professor Teresa Lambe OBE, lead senior author for these studies. ‘Here we show that a third dose of ChAdOx1 nCoV-19 is well tolerated and significantly boosts the antibody response. This is very encouraging news, if we find that a third dose is needed.’

Side effects of the vaccine itself were also found to be well-tolerated, with lower incidents of side effects after second and third doses than after first doses.

Further research is required to follow up with study participants who received third doses beyond the period that was part of the initial study.

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