Antibody levels vary according to vaccine type and previous infection with COVID-19

Two doses of the Oxford-AstraZeneca COVID-19 vaccine induce lower levels of antibodies that are able to recognise and fight the SARS-CoV-2 Delta variant (B.1.617.2) than against other strains. These laboratory findings from the National Institute for Health Research (NIHR) UCLH Biomedical Research Centre and the Francis Crick Institute are published as a Research letter in The Lancet.

Compared with results from the team’s recent investigation of Pfizer-BioNTech COVID-19 vaccine recipients, these data suggest that both vaccines induce lower levels of antibodies targeting the Delta variant. This trend was most marked for  the Oxford-AstraZeneca COVID-19 vaccine, the researchers found two doses of vaccine generate antibody levels that are 2.5x lower against the Delta variant than the Pfizer-BioNTech vaccine.

Levels of antibodies alone do not predict vaccine effectiveness but this study confirms that two doses of either vaccine are essential to boost antibodies to quantifiable levels that are likely to maximise the amount of protection against severe disease and hospitalisation.

Their results also show that antibody levels induced by the Oxford-AstraZeneca vaccine vary considerably depending on likely prior infection with SARS-CoV-2. They observed that people who had previously reported having symptoms of COVID-19, had higher antibody levels after their first vaccine dose.

These laboratory tests provide valuable insight into which groups of people are most at risk, even after both vaccine doses, and might require a booster vaccination. Researchers have submitted their findings to the Genotype-to-Phenotype National Virology Consortium (G2P-UK), the New and Emerging Respiratory Virus Threats Advisory Group (NERVTAG) and the Joint Committee on Vaccination and Immunisation (JCVI).

As part of the SARS-CoV-2 Legacy study, led by the Crick and partners at UCL and University College London Hospitals NHS Foundation Trust (UCLH), healthcare workers and staff from the institutions have been donating regular blood and swab samples so that researchers can track changing risk of infection and response to vaccination.

The Legacy team analysed the blood of 106 healthy people who received either one or two doses of the Oxford-AstraZeneca COVID-19 vaccine. Mirroring their analysis of Pfizer-BioNTech recipients, they used robust high throughput viral neutralisation assays developed at the Crick, to test the ability of antibodies to block entry of the virus into cells, so called ‘neutralising antibodies’, against five different variants of SARS-CoV-2:

• The original strain first discovered in Wuhan, China
• The dominant strain in Europe during the first wave in April 2020 (D614G)
• B.1.1.7, the variant first discovered in Kent, UK (Alpha)
• B.1.351, the variant first discovered in South Africa (Beta)
• B.1.617.2, the newest variant of concern, first discovered in India (Delta)

They then compared concentrations of these neutralising antibodies across all variants. Data from previous clinical studies suggests that higher antibody titres (the greatest dilution level that still blocks 50% of virus infection in the lab) is a good predictor of vaccine efficacy and greater protection against COVID-19.

They found that in people who had been fully vaccinated with two doses of the Oxford-AstraZeneca vaccine, nearly all participants had a quantifiable level (87% with >40 titre) of neutralising antibodies against the variants previously dominant in the UK (D614G and B.1.1.7). But significantly fewer people had quantifiable levels against the Beta and Delta variants (60% and 62% respectively). This contrasted with the Pfizer-BioNTech analysis, which showed that over 95% of recipients had quantifiable neutralising antibody levels against the Beta and Delta variants after both doses.

In people who had only received one dose of the Oxford-AstraZeneca vaccine, levels varied according to previous infection. Those with prior COVID-19 symptoms had significantly higher levels of neutralising antibodies against all strains, than those who hadn’t been infected. And, a significant proportion of people without prior COVID-19 symptoms had antibody levels below the limit of detection against new variants of concern (65% against B.1.1.7; 88% against B.1.351; and 85% against B.1.617.2). This variation was not seen in recipients of the Pfizer-BioNTech vaccine.

The people analysed in this part of the study were younger than average Oxford-AstraZeneca vaccine recipients (median age 34), so more research is needed to understand the antibody response in older people.

Dr Emma Wall, UCLH Infectious Diseases consultant and Senior Clinical Research Fellow for the Legacy study, said: “This is more evidence in support of ensuring everyone gets two doses of vaccine to protect against severe COVID-19, including reducing the gap between vaccine doses wherever supply and capacity allows. We can see clearly that the Delta variant poses a significant threat, but that two vaccine doses, and likely an additional booster, will be the best way to maximise protection, particularly against hospitalisations and deaths from COVID-19.

“These vaccines were designed based on the original strain first detected in China in 2019 so it is not surprising that we see different neutralising antibody levels against these new variants. No vaccine is 100% effective, so it will take more of us to be fully vaccinated to bring the spread of this newest variant under control.”

David LV Bauer, group leader of the Crick’s RNA Virus Replication Laboratory and member of the G2P-UK National Virology Consortium, said: “While many people have had COVID in the past, the new Delta variant is slightly different from the virus that people will have encountered in 2020 or early 2021. Our results underline how important it is for everyone to get vaccinated and to attend appointments for their second jab too.”

“Laboratory tests are vital to match and compare with the observational data we’re seeing in the community,” adds David.  “This will help us to understand which groups of people are most vulnerable and prioritise them for boosting in the future, if needed.”

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