Antibody Response in Immunocompromised Patients After the Administration of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Vaccine BNT162b2 or mRNA-1273: A Randomized Controlled Trial

Abstract

Background: BNT162b2 by Pfizer-BioNTech and mRNA-1273 by Moderna are the most commonly used vaccines to prevent severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections. Head-to-head comparison of the efficacy of these vaccines in immunocompromised patients is lacking.

Methods: Parallel, 2-arm (allocation 1:1), open-label, noninferiority randomized clinical trial nested into the Swiss HIV Cohort Study and the Swiss Transplant Cohort Study. People living with human immunodeficiency virus (PLWH) or solid organ transplant recipients (SOTR; ie, lung and kidney) from these cohorts were randomized to mRNA-1273 or BNT162b2. The primary endpoint was antibody response to SARS-CoV-2 spike (S1) protein receptor binding domain (Elecsys Anti-SARS-CoV-2 immunoassay, Roche; cutoff ≥0.8 units/mL) 12 weeks after first vaccination (ie, 8 weeks after second vaccination). In addition, antibody response was measured with the Antibody Coronavirus Assay 2 (ABCORA 2).

Results: A total of 430 patients were randomized and 412 were included in the intention-to-treat analysis (341 PLWH and 71 SOTR). The percentage of patients showing an immune response was 92.1% (95% confidence interval [CI]: 88.4-95.8; 186/202) for mRNA-1273 and 94.3% (95% CI: 91.2-97.4; 198/210) for BNT162b2 (difference: -2.2%; 95% CI: -7.1 to 2.7), fulfilling noninferiority of mRNA-1273. With the ABCORA 2 test, 89.1% had an immune response to mRNA-1273 (95% CI: 84.8-93.4; 180/202) and 89.5% to BNT162b2 (95% CI: 85.4-93.7; 188/210). Based on the Elecsys test, all PLWH had an antibody response (100.0%; 341/341), whereas for SOTR, only 60.6% (95% CI: 49.2-71.9; 43/71) had titers above the cutoff level.

Conclusions: In immunocompromised patients, the antibody response of mRNA-1273 was noninferior to BNT162b2. PLWH had in general an antibody response, whereas a high proportion of SOTR had no antibody response.

Keywords: HIV; SARS-CoV-2; organ transplant; platform trial; randomized controlled trial; vaccine.

Figure 1.

Flow chart. ^*3 patients who missed the study visits could be contacted by phone to assess clinical outcomes. ^aIncluding all patients because they were randomized and have available outcome data. ^bIncluding patients who received the intervention they were allocated to and have available outcome data. ^cIncluding patients who received the intervention they were allocated to, with an interval of 4 weeks (± 1 week) between first and second vaccination dose and provided outcome data at 12 weeks (± 1 week). Results only presented within appendix. Abbreviations: ITT, intention to treat; pp, per-protocol; SAE, serious adverse event.

Figure 2.

Antibody response in immunocompromised patients after receiving 2 doses of SARS-CoV-2 vaccines (per-protocol data set) using ABCORA 2 [15]. Figure shows combined reactivity of IgM, IgA, and IgG to the subunit S1 in patients who received the allocation they were randomized to and provided a blood sample at follow-up (per-protocol). Depicted are sum S1 (sum of S1 signal over cutoff values IgG, IgA, IgM) off all patients, patients from Swiss HIV Cohort Study (SHCS), Swiss Transplant Cohort Study (STCS). Box plots indicate the interquartile ranges with vertical lines representing the minimum and maximum values. ABCORA 2, Antibody Coronavirus Assay 2; Ig, immunoglobulin; SARS-CoV-2, severe acute respiratory syndrome coronavirus 2.