Antibody responses to the SARS-CoV-2 vaccine in individuals with various inborn errors of immunity

Abstract

Background SARS-CoV-2 vaccination is recommended in patients with inborn errors of immunity (IEI); however, little is known about immunogenicity and safety in these patients. Objectives To evaluate the impact of genetic diagnosis, age, and treatment on antibody response to COVID-19 vaccine and related adverse event (AE) in a cohort of patients with IEI. Methods Plasma was collected from twenty-two healthcare worker (HCW) controls, 81 IEI patients and 2 thymoma pre-immunization, 1 to 6 days prior to the second dose of mRNA vaccine and at a median of 30 days after completion of the immunization schedule with either mRNA vaccine or a single dose of Johnson & Johnson’s Janssen vaccine. Anti-Spike (S) and anti-Nucleocapsid (N) antibody titers were measured using a luciferase immunoprecipitation systems (LIPS) method. T and B cell counts and use of immunosuppressive drugs were extracted from medical records. Vaccine-associated AE were collected after each dose. Results Positive anti-S antibodies were detected in 27/46 (58.7%) of the patients after one dose of mRNA vaccine and in 63 of 74 (85.1%) fully immunized patients. A lower rate of seroconversion (7/11, 63.6%) was observed in patients APECED. Previous use of rituximab and baseline counts of <1,000 CD3 + T cells/μL and <100 CD19 + B cells/μL were associated with lower anti-S IgG levels. No significant adverse events were reported. Conclusion Vaccinating IEI patients is safe, but immunogenicity is impacted by certain therapies and gene defects. These data may guide counseling IEI patients on prevention of SARS-CoV-2 infection and need for subsequent boosts.

The Immune Response to SARS-CoV-2 Vaccination: Insights Learned From Adult Patients With Common Variable Immune Deficiency

“…The only patient who failed to have a substantial rise in post vaccination titers had a marked decrease in the frequency of circulating B cells ( 25 ). In a recent paper, a high percentage of fully immunized CVID patients developed anti-Spike IgG, at significantly lower levels than in the healthy control group ( 26 ). Our data ( 27 ) in CVID patients immunized with BNT162b2 SARS-CoV-2 mRNA vaccine contrasted with the high frequency of response reported in the cohorts illustrated above.…”

“…Since vaccination became available, Italian CVID patients, as well as CVID from other countries, were immunized mostly with mRNA COVID-19 vaccines. Four groups have recently reported immune responses to vaccines in patients with inborn errors of immunity, including CVID patients (24)(25)(26)(27). In the study by Hagin et al, 70% of the adult patients with predominantly antibody deficiency developed specific humoral and T-cell responses after 2 doses of SARS-CoV-2 mRNA vaccine.…”

Autoimmune Polyendocrinopathy-Candidiasis-Ectodermal Dystrophy

“…Collectively, these reports indicate that APECED patients, particularly adults and/or those with underlying pneumonitis, can be at risk for severe COVID-19. Therefore, APECED patients should be prioritized for vaccination against SARS-CoV-2, which they appear to tolerate without unusual adverse events; however, it is important to note that not all APECED patients develop robust humoral responses to the SARS-CoV-2 vaccine, especially those receiving immunomodulatory therapy ( 103 ). In our experience with SARS-CoV-2–infected APECED patients at the NIH Clinical Center, we proceed with prophylactic hospital admission upon diagnosis for close clinical monitoring.…”

Authors’ response

“…3,4 Our patients with CVID have been followed up for more than 6 months since having completed the 2dosage mRNA vaccine schedule, and none of them have developed or had flare-ups of autoimmune or other long-term inflammatory conditions; other studies have reported reassuring safety data as well. 2,5,6 Furthermore, patients with rheumatologic diseases who have a myriad of autoimmune conditions have been thus far safely vaccinated with mRNA vaccines, with no apparent impact on disease activity and no further safety concerns in the short term. 7,8 Severe adverse events, albeit rare, may nonetheless occur after vaccination, regardless of preexisting medical conditions.…”