A third of leukaemia patients 'do not generate antibody response to two doses of Covid jab '

A University of Birmingham-led study has shown that a third of patients with the most common type of leukaemia fail to generate any measurable antibody response following two doses of Covid-19 vaccination.

Furthermore, the research showed that in the two thirds of patients who do develop antibodies, levels are much lower than compared to healthy people and also have a profoundly reduced ability to 'neutralise ' the globally dominant Delta variant.

The research identified a number of important new findings which researchers say will be crucial to shaping future management and public health policy for patients with this type of blood cancer, who are immunosuppressed and at an increased clinical risk from SARS-CoV-2 infection.

Key new findings are:

• Only 67 per cent of the leukaemia patients generated any measurable antibody response to double Covid-19 vaccination, compared to 100 per cent of the age-matched healthy population.

• In those patients with leukaemia who did have an antibody response, antibody levels were 3.7 times lower than that seen in the healthy control group.

• Antibody levels declined by 33 per cent at four months after leukaemia patients ' second vaccine.
• No difference in antibody responses were observed between those participants receiving the Oxford/AstraZeneca vaccine and those receiving the Pfizer/BioNTech vaccine.

• Antibody responses showed weak ability to neutralise the spike protein from the now globally dominant SARS-CoV-2 Delta variant compared to healthy controls.

Five-hundred patients with chronic lymphocytic leukaemia - the most common leukaemia in adults - were recruited to the study.

41 per cent had received two doses of the Pfizer/BioNTech vaccine, whilst 59% had received two doses of the Oxford/AstraZeneca vaccine.

The average age of participants was 67 and 53 per cent of the cohort was male.

Their antibody response to double Covid-19 vaccination was compared to that of 94 age-matched healthy 'controls '.

Blood samples were obtained from all study participants between two to three weeks following their second vaccination, and again up to 30 weeks later.

Antibody responses were seen in 67 per cent (336) of the leukaemia patients, compared to 100% (93) of age-matched controls.

In those with leukaemia who did generate an antibody response, the average antibody level was 3.7 times lower in magnitude and only just over a quarter (27 per cent) of that seen in the healthy controls.

Using serum samples of 94 of the leukaemia patients, and 94 healthy controls, the team also analysed their ability to neutralise live SARS-CoV-2 infection in the laboratory using the original Wuhan virus and the Delta variant.

In the healthy cohort, average neutralisation of live Wuhan and Delta virus was 96 per cent and 84 per cent respectively.

However, in the leukaemia patients, neutralisation of Wuhan virus was only 62 per cent and even lower at 14 per cent in the Delta variant.

Dr Helen Parry (pictured), a National Institute for Health Research (NIHR) academic clinical lecturer at the University of Birmingham, said: “It is concerning that 33 per cent of patients in our study did not generate any measurable antibody response to two doses of Covid-19 vaccination, and particularly concerning that in those who did generate an antibody response, there was a profound loss in ability to neutralise live Delta variant.

“The Delta variant is now globally dominant and more than twice as contagious as the Wuhan virus. Current Covid-19 vaccines are based on the spike protein sequence from the original Wuhan virus, whereas the Delta variant contains additional mutations. ”

Meanwhile, antibody titers in leukaemia patients who had previously been infected with Covid-19 were 21-times higher than those seen in patients without previous infection - revealing strong immunological 'priming ' after natural infection.

The leukaemia patients without previous Covid-19 infection had equal antibody responses, no matter which of the two vaccines types they had been given.

The research, published as a pre-print and therefore yet to be peer reviewed, was funded by the National Core Studies Immunity programme which is funded by the UK Research and Innovation (UKRI).

It was also partially supported by UK-CIC which is jointly funded by UKRI and the National Institute for Health Research (NIHR).