Background Patients on therapeutic immunosuppressants for immune-mediated inflammatory diseases were excluded from COVID-19 vaccine trials. We therefore aimed to evaluate humoral and cellular immune responses to COVID-19 vaccine BNT162b2 (Pfizer-BioNTech) in patients taking methotrexate and commonly used targeted biological therapies, compared with healthy controls. Given the roll-out of extended interval vaccination programmes to maximise population coverage, we present findings after the first dose. MethodsIn this cohort study, we recruited consecutive patients with a dermatologist-confirmed diagnosis of psoriasis who were receiving methotrexate or targeted biological monotherapy (tumour necrosis factor [TNF] inhibitors, interleukin [IL]-17 inhibitors, or IL-23 inhibitors) from a specialist psoriasis centre serving London and South East England. Consecutive volunteers without psoriasis and not receiving systemic immunosuppression who presented for vaccination at Guy's and St Thomas' NHS Foundation Trust (London, UK) were included as the healthy control cohort. All participants had to be eligible to receive the BNT162b2 vaccine. Immunogenicity was evaluated immediately before and on day 28 (±2 days) after vaccination. The primary outcomes were humoral immunity to the SARS-CoV-2 spike glycoprotein, defined as neutralising antibody responses to wild-type SARS-CoV-2, and spike-specific T-cell responses (including interferon-γ, IL-2, and IL-21) 28 days after vaccination.

COVID-19 vaccine design and vaccination rollout need to take into account a detailed understanding of antibody durability and cross-neutralizing potential against SARS-CoV-2 and emerging variants of concern (VOCs). Analyses of convalescent sera provide unique insights into antibody longevity and cross-neutralizing activity induced by variant spike proteins, which are putative vaccine candidates. Using sera from 38 individuals infected in wave 1, we show that cross-neutralizing activity can be detected up to 305 days pos onset of symptoms, although sera were less potent against B.1.1.7 (Alpha) and B1.351 (Beta). Over time, despite a reduction in overall neutralization activity, differences in sera neutralization potency against SARS-CoV-2 and the Alpha and Beta variants decreased, which suggests that continued antibody maturation improves tolerance to spike mutations. We also compared the cross-neutralizing activity of wave 1 sera with sera from individuals infected with the Alpha, the Beta or the B.1.617.2 (Delta) variants up to 79 days post onset of symptoms. While these sera neutralize the infecting VOC and parental virus to similar levels, cross-neutralization of different SARS-CoV-2 VOC lineages is reduced. These findings will inform the optimization of vaccines to protect against SARS-CoV-2 variants.

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Summary Patients receiving targeted cancer treatments such as tyrosine kinase inhibitors (TKIs) have been classified in the clinically extremely vulnerable group to develop severe acute respiratory syndrome coronavirus‐2 (SARS‐CoV‐2), including patients with chronic myeloid leukaemia (CML) taking TKIs. In addition, concerns that immunocompromised individuals with solid and haematological malignancies may not mount an adequate immune response to a single dose of SARS‐CoV‐2 BNT162b2 (Pfizer‐BioNTech) vaccine have been raised. In the present study, we evaluated humoral and cellular immune responses after a first injection of BNT162b2 vaccine in 16 patients with CML. Seroconversion and cellular immune response before and after vaccination were assessed. By day 21 after vaccination, anti‐Spike immunoglobulin G was detected in 14/16 (87·5%) of the patients with CML and all developed a neutralising antibody response [serum dilution that inhibits 50% infection (ID 50 ) >50], including medium (ID 50 of 200–500) or high (ID 50 of 501–2000) neutralising antibodies titres in nine of the 16 (56·25%) patients. T‐cell response was seen in 14/15 (93·3%) evaluable patients, with polyfunctional responses seen in 12/15 (80%) patients (polyfunctional CD4 + response nine of 15, polyfunctional CD8 + T‐cell response nine of 15). These data demonstrate the immunogenicity of a single dose of SARS‐CoV‐2 BNT162b2 vaccine in most patients with CML, with both neutralising antibodies and polyfunctional T‐cell responses seen in contrast to patients with solid tumour or lymphoid haematological malignancies.

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