Researchers in the UK have provided evidence that Pfizer-BioNTech’s coronavirus disease 2019 (COVID-19) vaccine induces effective immune responses in patients with myeloproliferative neoplasms.
The team from Guy’s & St Thomas’ NHS Foundation Trust in London and King’s College London say the findings are reassuring, given that concerns have arisen regarding the efficacy of such vaccines in immunosuppressed individuals, including those with hematological malignancy.
“Myeloproliferative neoplasms (MPN), in particular myelofibrosis (MF), are associated with heterogeneous immune defects which are influenced by patient age, disease subtype, and the use of cytoreductive therapies,” write the researchers.
Now, Patrick Harrington and colleagues report that of 21 patients with MPN who received the first dose of Pfizer-BioNTech’s BNT162b2 vaccine, 18 (86%) exhibited neutralizing antibody activity against the spike protein of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) – the agent that causes COVID-19.
The spike protein is the main structure the virus uses to infect host cells and a primary target of neutralizing antibodies following natural infection or vaccination.
Sixteen (76%) of the patients also exhibited a memory T cell response following vaccination.
“These results, for the first time, provide some reassurance regarding the initial immune response to the BNT162b2 vaccine amongst patients with MPN, with response rates similar to that observed in the general population,” writes the team.
A pre-print version of the research paper is available on the medRxiv* server, while the article undergoes peer review.
Concerns about vaccine effectiveness in immunocompromised individuals
Phase 3 clinical trials of vaccines targeting SARS-CoV-2 have generated encouraging results, with the BNT162b2 vaccine from Pfizer-BioNTech having been shown to reduce infection rates by 95% in the general population.
However, concerns have arisen regarding the efficacy of these vaccines in immunosuppressed populations, including individuals with hematological malignancy.
MPN and particularly MF have been associated with a pro-inflammatory state and the dysregulation of natural killer cells, regulatory T cells, and effector T cell function
These defects are further influenced by age, the use of cytoreductive therapies and the stage and subtype of disease.
A recent large-scale population-based study reported that the incidence of both bacterial and viral infections was significantly increased among patients with MPN, irrespective of the use of cytoreductive therapies.
Another large prospective study found that MF diagnosis and the use of ruxolitinib therapy were associated with an increased risk of infection among MPN patients.
“These studies highlight the importance of an effective vaccination program against SARS-CoV-2 in this population,” says Harrington and the team.
What did the researchers do?
The researchers administered one dose of the BNT162b2 vaccine to 21 patients with a WHO-defined diagnosis of an MPN.
They performed an enzyme-linked immunosorbent assay (ELISA) to test for anti-spike immunoglobulin G (IgG) antibodies at baseline and at a median of 21 days following vaccination.
The induction of virus-specific T-cell responses and neutralizing antibodies was also assessed.
What did they find?
The team reports that vaccination was safe and generally well-tolerated. Twelve (57%) patients reported localized inflammation, and ten (47.6%) reported systemic side effects, including flu-like illness, fatigue and gastrointestinal symptoms.
A positive anti-spike IgG ELISA was observed in 16 (76%) patients following vaccination and neutralizing antibodies were detected in 18 (86%) patients.
Furthermore, high titers of neutralizing antibodies were observed in nine (42.9%) patients.
What about T cell responses?
T cell analysis was performed in 20 patients, with a response considered positive if levels of pro-inflammatory cytokines increased 3-fold from baseline.
A memory T cell response was observed in 16 (80%) patients, with a CD4+ T cell response observed in 15 (75%) individuals and a CD8+ T cell response observed in seven (35%). A polyfunctional T cell response was also observed in 13 (65%) of the patients.
“A memory T cell response may prove to be particularly important with regards to ongoing immunity against SARS-CoV-2,” say the researchers. “Our group has demonstrated a marked decline in neutralizing antibodies in the 3 months following infection, while a robust T cell response remains evident at 6 months post-infection.”
No significant differences in T cell or antibody responses were observed between patients receiving treatment and those undergoing active surveillance. Similarly, no significant differences were observed between patients taking ruxolitinib and those receiving other therapies.
The team says the findings are reassuring
The team says the findings are the first to provide some reassurance regarding the initial immune response to the BNT162b2 vaccine amongst patients with MPN, with response rates similar to that observed in the general population.
However, “further analyses of the immune response to the second injection of BNT162b2, as well as the response to other vaccines against SARS-CoV-2, are clearly required,” writes Harrington and colleagues.
“Longitudinal studies will also need to assess the durability of these responses and confirm that vaccination translates into a reduction in cases in this population,” they conclude.
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.