Safety and efficacy of the mRNA BNT162b2 vaccine against SARS-CoV-2 in five groups of immunocompromised patients and healthy controls in a prospective open-label clinical trial

Abstract

Background: Patients with immunocompromised disorders have mainly been excluded from clinical trials of vaccination against COVID-19. Thus, the aim of this prospective clinical trial was to investigate safety and efficacy of BNT162b2 mRNA vaccination in five selected groups of immunocompromised patients and healthy controls.

Methods: 539 study subjects (449 patients and 90 controls) were included. The patients had either primary (n=90), or secondary immunodeficiency disorders due to human immunodeficiency virus infection (n=90), allogeneic hematopoietic stem cell transplantation/CAR T cell therapy (n=90), solid organ transplantation (SOT) (n=89), or chronic lymphocytic leukemia (CLL) (n=90). The primary endpoint was seroconversion rate two weeks after the second dose. The secondary endpoints were safety and documented SARS-CoV-2 infection.

Findings: Adverse events were generally mild, but one case of fatal suspected unexpected serious adverse reaction occurred. 72.2% of the immunocompromised patients seroconverted compared to 100% of the controls (p=0.004). Lowest seroconversion rates were found in the SOT (43.4%) and CLL (63.3%) patient groups with observed negative impact of treatment with mycophenolate mofetil and ibrutinib, respectively.

Interpretation: The results showed that the mRNA BNT162b2 vaccine was safe in immunocompromised patients. Rate of seroconversion was substantially lower than in healthy controls, with a wide range of rates and antibody titres among predefined patient groups and subgroups. This clinical trial highlights the need for additional vaccine doses in certain immunocompromised patient groups to improve immunity.

Funding: Knut and Alice Wallenberg Foundation, the Swedish Research Council, Nordstjernan AB, Region Stockholm, Karolinska Institutet, and organizations for PID/CLL-patients in Sweden.

Keywords: CAR-T; HIV; Immunocompromised patients; Primary Immunodeficiency; chronic lymphocytic leukemia; human stem-cell transplantation; mRNA BNT162b2 vaccine; solid organ transplantation.

Figure 1

Flowchart of the study. The chart depicts the groups of study subjects screened prior to the study and the specific groups being enrolled and studied. Side-effects that precluded dose 2 (n=5) were vasovagal reaction leading to voluntary withdrawal (WP2), and thrombocytopenia, GvHD, elevated liver enzymes, and SUSAR (all in WP3).

Figure 2

Seroconversion and antibody titres per patient group and in healthy controls. a) Seroconversion in the five immunocompromised groups and control group defined as ≥ 0.8 U/ml assessed in the modified per protocol (mPP) population. b) Median SARS-CoV-2 specific antibody titres in the five immunocompromised groups and control group. c) Median (CI 95%) SARS-CoV-2 specific antibody titres at day 35 in individuals who seroconverted. D) Individual antibody dynamics (black thin lines) with median interquartile range (IQR) (coloured thick lines) for each respective group. X-axis: days after first vaccination if not else noted.

Figure 3

Seroconversion and antibody titres in subgroups of the specific patient groups. a) Seroconversion in the specific subgroups defined as ≥ 0.8 U/ml in the modified per protocol (mPP) population (see right column for subgroup classification). b) Individual SARS-CoV-2 specific antibody titres for each timepoint in the respective subgroups. Dotted lines represent upper (25,000 U/ml) and lower (0.4 U/ml) limits of detection. Dashed line represents seroconversion threshold of 0.8 U/ml.