Immunogenicity of Anti-SARS-CoV-2 Vaccines in Common Variable Immunodeficiency

Abstract

Common variable immunodeficiency (CVID) is characterized by hypogammaglobulinemia and/or a defective antibody response to T-dependent and T-independent antigens. CVID response to immunization depends on the antigen type, the vaccine mechanism, and the specific patient immune defect. In CVID patients, humoral and cellular responses to the currently used COVID-19 vaccines remain unexplored. Eighteen CVID subjects receiving 2-dose anti-SARS-CoV-2 vaccines were prospectively studied. S1-antibodies and S1-specific IFN-γ T cell response were determined by ELISA and FluoroSpot, respectively. The immune response was measured before the administration and after each dose of the vaccine, and it was compared to the response of 50 healthy controls (HC). The development of humoral and cellular responses was slower in CVID patients compared with HC. After completing vaccination, 83% of CVID patients had S1-specific antibodies and 83% had S1-specific T cells compared with 100% and 98% of HC (p = 0.014 and p = 0.062, respectively), but neutralizing antibodies were detected only in 50% of the patients. The strength of both humoral and cellular responses was significantly lower in CVID compared with HC, after the first and second doses of the vaccine. Absent or discordant humoral and cellular responses were associated with previous history of autoimmunity and/or lymphoproliferation. Among the three patients lacking humoral response, two had received recent therapy with anti-B cell antibodies. Further studies are needed to understand if the response to COVID-19 vaccination in CVID patients is protective enough. The 2-dose vaccine schedule and possibly a third dose might be especially necessary to achieve full immune response in these patients.

Keywords: COVID-19; Common variable immunodeficiency; Immunogenicity; Primary immunodeficiency diseases; SARS-CoV-2; Vaccination.

Fig. 1

Study design and schedule. A 1st immune response test. B Immunoglobulin administration. C 1st vaccination dose. D 2nd immune response test. E Immunoglobulin administration. F 2nd vaccination dose. G Immunoglobulin administration. H 3rd immune response test

Fig. 2

Clinical manifestations in CVID patients. Each category does not exclude other manifestations in the same patient. Number of patients by manifestation: infections = 15; autoimmunity = 6; splenomegaly = 6; lymphoproliferation = 4; solid organ tumor = 4; bronchiectasis = 2; lymphoma = 2; cytopenias = 1

Fig. 3

Immune response rate in CVID patients. a S1-specific humoral response rate; b S1-specific cellular response rate; c S1-specific humoral response rate in CVID clinical subgroups; d S1-specific cellular response rate in CVID clinical subgroups. HC, healthy controls; CVID, common variable immunodeficiency; CVID Inf, CVID with only infections; CVID A/L, CVID with autoimmunity/lymphoproliferation. ns, not significant; * = p < 0.05; ** = p < 0.01; *** = p < 0.001

Fig. 4

Strength of immune response in CVID patients. a Anti-S1 antibodies; b anti-S1 IFN-γ T cells; c anti-S1 antibodies in CVID subgroups; d anti-S1 IFN-γ T cell in CVID subgroups. Dotted lines represent positivity cut-off: ≥ 1.1 ratio of OD for anti-S1 antibodies and > 25 IFN-γ SFU/10⁶ PBMCs for S1-specific IFN-γ T cells response. HC, healthy controls; CVID, common variable immunodeficiency; CVID Inf, CVID with only infections; CVID A/L, CVID with autoimmunity/lymphoproliferation. ns, not significant; * = p < 0.05; ** = p < 0.01; *** = p < 0.001