Single dose of Pfizer-BioNTech COVID-19 vaccine induces immunity in CML patients

Researchers in the UK have shown that a single dose of the Pfizer-BioNTech vaccine against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) induced antibody and cellular responses in patients with chronic myeloid leukemia (CML) who were taking tyrosine kinase inhibitors.

The novel SARS-CoV-2 virus is the agent responsible for the coronavirus disease 2019 (COVID-19) pandemic that has now claimed the lives of more than 3 million people globally.

Patients receiving cancer treatments such as tyrosine kinase inhibitors (TKIs) are classified as clinically highly vulnerable to developing severe COVID-19, including those with CML.

Studies have previously shown that CML patients have impaired adaptive and innate immunity and that TKIs may weaken vaccine-induced immune responses to SARS-CoV-2 infection.

Concerns have therefore arisen that individuals receiving TKIs may not mount an adequate immune response following a single dose of vaccination

Now, a team from Guy’s & St Thomas’ NHS Foundation Trust and London King’s College London has found that of 16 patients with CML patient taking TKIs, all developed neutralizing antibody responses, and 14 developed T cell responses against SARS-CoV-2 infection 21 days following a single dose of the Pfizer-BioNTech BNT162b2 vaccine.

“To our knowledge, this is the first report of humoral and T-cell response to vaccination against SARS-CoV-2 in patients with CML taking TKIs,” writes Hugues de Lavallade and colleagues.

A pre-print version of the research paper is available on the medRxiv* server, while the article undergoes peer review.

More about the Pfizer-BioNTech vaccine and CML

Since the novel SARS-CoV-2 virus was first identified in Wuhan, China, in late December 2021, the COVID-19 pandemic has posed unprecedented healthcare challenges and caused more than 3.1 million deaths globally.

The development of immunity against the virus is key to reducing transmission. Impressive collaborative efforts have led to the rapid development of several effective vaccines currently being rolled out worldwide.

The messenger RNA (mRNA)-based Pfizer-BioNTech BNT162b2 vaccine encodes the full-length SARS-CoV-2 spike protein that the virus uses to infect cells. This spike structure is a key target of neutralizing antibodies following natural infection or vaccination.

However, concerns that immunocompromised individuals may not mount an adequate immune response to the spike protein following a single dose of vaccination have been raised.

Patients with CML have been shown to have impaired innate and adaptive immunity, which led to this patient group being classified as “clinically extremely vulnerable” to developing severe COVID-19 by the Department of Health and Social Care (DHSC).

Furthermore, immune responses to vaccination may be attenuated by TKIs, especially those with more significant “off-target” kinase inhibition, which the researchers previously showed inhibits B cell function and antibody responses in vivo.

What did the current study involve?

Lavallade and colleagues assessed humoral (antibody) and cellular immune responses 21 days following the first injection of BNT162b2 vaccine among 16 CML patients on TKI therapy who were recruited between 17^th December 2020 and 17^th February 2021.

The vaccine was safe and tolerable, with localized inflammation reported by nine patients (56.3%) and a transient flu-like illness reported by four (23.5%) patients.

By day 21 following vaccination, 14 (87.5%) patients had developed detectable levels of anti-spike immunoglobulin G (IgG), and all patients had developed a neutralizing antibody response. Seven patients (43.8%) had low titers of neutralizing antibodies, three (18.8%) had medium titers and six (37.5%) had high titers.  

What about T cell responses?

A memory T cell response was seen in 14 of 15 (93.3%) evaluable patients. The only participant not showing a T-cell response had undergone allogeneic hematopoietic stem cell transplantation.

A SARS-CoV-2-specific CD4+ T cell response was observed in twelve (80%) of the 15 patients, and a SARS-CoV-2 specific CD8+ T cell response was observed in nine (60%) patients. A polyfunctional CD4+ or CD8+ T cell response was also observed in twelve of the patients.

“These data demonstrate the immunogenicity of a single dose of SARS-CoV-2 BNT162b2 vaccine in most CML patients with both neutralizing antibodies and polyfunctional T-cell responses seen,” writes Lavallade and the team.

The findings have important implications

The researchers say these data are particularly important in the context of the decision from the DHSC to increase the interval between a first and a second vaccine dose. The findings suggest that CML patients taking TKIs exhibit significant immune responses following just one dose of the BNT162b2 vaccine.

“Additional studies will need to determine if the immune response will be sufficient to protect against emerging variants, as well as to analyze the effect of other currently available and emerging vaccines against SARS-CoV-2,” concludes the team.

*Important Notice

medRxiv publishes preliminary scientific reports that are not peer-reviewed and, therefore, should not be regarded as conclusive, guide clinical practice/health-related behavior, or treated as established information.

Written by

Sally Robertson

Sally first developed an interest in medical communications when she took on the role of Journal Development Editor for BioMed Central (BMC), after having graduated with a degree in biomedical science from Greenwich University.