Good news on vaccine efficacy for the 80%

[Me2AsWell]

A letter in "Cancer Cell" (sounds like a pretty malicious PP prison) from the Birmingham-based research team to whom we were sending blood.

Topic: COVID-19 vaccines elicit robust cellular immunity and clinical protection in chronic lymphocytic leukemia

Following Minto's principle, I'll start with the conclusion (the news that matters): "In conclusion, SARS-CoV-2 vaccines are currently providing good clinical protection for patients with CLL, but approximately 20% of patients are refractory to seroconversion and are at increased risk of infection. In contrast, cellular responses after vaccination are comparable with those of healthy donors and may be critical for preventing severe disease."

cell.com/cancer-cell/pdf/S1...

Extracts:

Spike-specific antibody responses have previously been reported to develop in

66% (322/486) of patients within the CLL-VR study following the first two vaccine

doses compared to 100% of controls (Parry et al., 2021). This response rate

improved to 80% following the third vaccine dose (298/374) (p < 0.0001) (Figure

S1A). Analysis of vaccine subtype received during the first two doses showed no

difference in seroconversion rate following a heterologous or homologous third dose (ChAdOx1/mRNA response rate 81% [187/230] vs. BNT162b2/mRNA response rate 77% [111/144], p = 0.28).

However, the seroconversion rate was not increased further after a fourth vaccine

(77%; 132/171), and this indicates that the proportion of patients who develop a

spike-specific antibody response following COVID-19 vaccination plateaus after the third vaccine . ... Regardless of vaccine dose number, a low serum IgM, current BTKi therapy, or imminent planned treatment were independent predictors of poor response with an 81% (p = 0.003), 90% (p = 0.021), and 96% (p = 0.027) reduction in

odds of response respectively after the fourth dose.

[annmcgowan]

Hi thanks for this information. I have had an antibody test after my 4th vaccine, which showed no antibodies. Does this mean I am one of the 20% that remain unprotected by vaccines?Ann

[JEEA in reply to annmcgowan]

I took part in this Birmingham study and yesterday received an email with the copy of the paper we have the link to. They also included this Clinical Interpretation of the results that is useful to read. Interesting about T-cell responses which may be positive for you, Ann? Also interesting is that if you received Astra Zeneca for your first two vaccines, you do better antibodies on your boosters.

I can't see how to attach the document, so have copied and pasted in the 'findings' which are useful to read.

Eleanor

"Findings of the Study

Antibody data

• 80% of participants had a detectable antibody response following the 3rd

dose. This is an improvement from 67% observed following the second dose.

However, it is still lower than the value of 100% in healthy age-matched

‘control’ people.

• Importantly this means that 20% of participants do not make a detectable

response.

• Following the 4th dose, the response rate reaches a plateau and no further

improvement in response rate is seen.

• Amongst participants with an antibody response after the 3rd primary

dose, the level of response was equivalent to values in the ‘control’ group

after 2 doses.

• There was no difference after the 3rd dose in the antibody responses

between patients who received the Pfizer-BioNTech or Oxford-AstraZeneca

for the first 2 doses.

• Three factors continued to predict for a negative antibody response after 3rd

and 4th vaccine dose in participants:

o Patients on Bruton tyrosine kinase inhibitor (such as ibrutinib or

acalabrutinib)

o Patients who were about to start treatment

o Those who were found to have low levels of Immunoglobulin M (IgM)

in their blood

• Post 3rd dose vaccine blood samples show a comparable ability to

neutralise the original Wuhan virus as control subjects. Although

neutralisation of Omicron is much lower, it remains equivalent between

patients and controls.

Cellular immune responses

• Cellular T cell responses improve following the 3rd vaccination and the level of

response is comparable to controls following their 2nd dose of vaccine.

• Participants who received the Oxford Astrazeneca vaccine for their first 2

doses had higher cellular responses following the second and third vaccine

doses.

• The cellular responses detected following the 3rd dose of vaccine showed

comparable responses against the Omicron variant and Wuhan virus.

Infection data

• 14% (66/486) of the patient cohort have experienced an episode of COVID-19

infection since receiving their first vaccine dose.

• The rate of breakthrough infections has increased substantially since Omicron

emerged, with 59% of all cases of infection occurring in a 3 month period

since December 2021 (39/66)

• The rate of hospitalisation has fallen to 13% since Omicron emerged

compared to 32% with earlier waves

• Only around half of participants have accessed treatment for their COVID-19

infection over the past 3 months.

• Surprisingly, we found that patients with a positive antibody test following 2

doses of vaccine were 70% more likely to suffer a breakthrough COVID-19

infection. However, this group was younger and it may reflect differences in

shielding behaviour and social mixing.

Implications from these findings so far:

• Antibody responses following dual Covid-19 vaccination are improved in

patients with CLL following the 3rd dose but 20% still lack an antibody

response and this does not improve with a further dose.

• Those with low serum immunoglobulins, taking BTKi or about to start therapy

appear most at risk for failing to generate an antibody response.

• The poor Omicron neutralisation following the 3rd vaccine dose suggests an

ongoing risk of infection.

• There has been an increase in breakthrough infections since Omicron

emerged but hospitalisation rates are falling. However, these remain above

rates seen in the general population.

• It remains difficult to provide advice for individual patients as to the

protective value of individual antibody or cellular immune measurements

• Patients should be advised to continue to follow nationally recommended

precautions to prevent catching infection

• We advise patients with CLL to do a lateral flow test if they develop any

symptoms suggestive of COVID-19 and access COVID medications from the

COVID Medications Delivery Units at the earliest opportunity.

Dr Helen Parry

Dr Graham McIlroy

Professor Guy Pratt

Dr Shankara Paneesha

Professor Paul Moss

[annmcgowan in reply to JEEA]

Thank you for your print and helpful reply. I took part in this study to and have just received my email. I will give it a thorough read.Take care

Ann

[Psmithuk]

Thank you, I received this and found their summary very helpful, although what would be more helpful would be knowing if I’ve made any antibodies and how many we need!Chris

[Fran57]

Thanks so much to you, and to Eleanor, for this information… it does sound, at a first reading, a lot more encouraging.Thank you, again.

Stay safe,

Fran 😷😉

[CLLerinOz Administrator Volunteer]

Thanks, Me2AsWell for sharing this report and JEEA for adding the Clinical Interpretation for the study. The interpretation summary is a reminder that:

'It remains difficult to provide advice for individual patients as to the protective value of individual antibody or cellular immune measurements.

• Patients should be advised to continue to follow nationally recommended precautions to prevent catching infection

• We advise patients with CLL to do a lateral flow test if they develop any symptoms suggestive of COVID-19 and access COVID medications from the COVID Medications Delivery Units at the earliest opportunity.'

There is also an earlier post that included some discussion about the study's findings:

healthunlocked.com/cllsuppo...

[CLLerinOz Administrator Volunteer in reply to CLLerinOz]

The UK Covid-19 Vaccine Research Hub has recently released a helpful Q&A list in response to the findings of this Birmingham study. Questions include:

Would ‘treatment holidays’ be viable for people with CLL (as have been tested in people with other conditions) to give them a chance to mount an immune response?

T cell responses were generally shown to be good in this study – would a good T cell response alone give someone adequate protection?

Should people with CLL still be shielding?

The answers to these and other questions can be found here:

covidvaccineresearch.org/q-...

[mrsjsmith in reply to CLLerinOz]

Thank you will read with interest.

Update just read and recommend everyone reads it. Very useful.

Colette

[SERVrider]

I got the paper, too; I'm male, have miniscule levels of IgM and am on a BTKi. On the basis of the study, I likely have bugger-all immunity from the vaccinations but I have played safe and had my fifth. 2 O-AZ, 2 Pfizer BioNTech and now 1 Moderna. Belt and braces.

[mrsjsmith in reply to SERVrider]

Sadly in the same boat as you, with the exception of being male. Interesting that is another poor indication for antibodies.

Colette

[SERVrider in reply to mrsjsmith]

Well, just keep taking the tablets!