Successful Anti-SARS-CoV-2 Spike Protein Antibody Response to Vaccination in MAGT1 Deficiency

Abstract

Background Novel messenger RNA vaccines against severe acute respiratory syndrome coronavirus (SARS-CoV-2) have been vital in resolving the coronavirus disease-2019 (COVID-19) pandemic. Detection of neutralizing antibodies (NAbs) against the SARS-CoV-2 spike protein (S) confirms immunogenicity with high sensitivity and specificity. Few recent studies with primary and secondary immunodeficient cohorts present adequate or reduced antibody response. We describe the first reported successful response to anti-SARS-CoV-2 S antibody post-vaccination in magnesium transporter 1 (MAGT1) gene deficiency, more commonly recognized as x-linked immunodeficiency with magnesium defect, Epstein-Barr Virus infection, and neoplasia (XMEN). Case Presentation We present a 30-year-old male with selective anti-polysaccharide antibody deficiency, peripheral blood CD5 + /CD19 + B-cell predominance (97%), MAGT1 mutation, and reduced CD16 + CD56 + natural killer- and/or CD8 + T-cell receptor, Group 2, Member D expression. His initial immunological evaluation revealed all seronegative post-vaccination antibody titers but clinically adequate response to protein antigens tetanus and diphtheria anti-toxoids. COVID-19 vaccination and associated serology antibody testing was recommended at this office visit. Anti-SARS-CoV-2 immunoglobulin (Ig)M and IgG antibodies before and after the first BNT162b2 mRNA COVID-19 vaccine doses, as well as nucleocapsid antibody, were negative. S protein total antibody was reactive after the second dose. Discussion Robust immunological sequelae post-COVID-19 vaccination in the general population are well-documented in the recent literature. Few studies have evaluated COVID-19 vaccination antibody response in immunodeficient patients. The majority positive anti-S antibody detection in most primary immunodeficient (PID) patients among the few studies in the literature, such as the present case, support the safety and efficacy of mRNA COVID-19 vaccination in immunodeficient patients, although larger scale studies are needed. 
 Conclusion We demonstrate successful vaccination in the PID MAGT1 deficiency in this first reported case of reactive anti-S antibody post-COVID-19 vaccination.

COVID-19 and Inborn Errors of Immunity

“…Besides CVID, data on the immunogenicity of the SARS-CoV-2 vaccine in patients with IEI are few and often limited to anecdotal cases or heterogeneous cohorts. Table 2 summarizes the available literature ( 19 – 21 , 23 , 89 , 120 , 121 , 124 , 128 ). Except for patients with XLA and combined immunodeficiency, most patients with IEI can produce anti-Spike antibodies following two vaccine doses.…”

An Overview of the Immune Response to COVID-19 Vaccination and Strategies to Boost SARS-CoV-2 Immunity in People with Inborn Errors of Immunity

“…This is important because otherwise, known age-related changes in the immune system would confound the results of each study. The published study designs varied from observational [71,77,[83][84][85][86][87][88][89][90][91][92][93][94][95][96] to interventional studies and clinical trials [80,82,83,97,98]. Furthermore, humoral responses were reported by seroconversion, antibody concentration/titers, and, in some cases, virus neutralization/pseudo-neutralization capacity (Figure 3 and Table 2).…”

“…For example, one report of individuals with STAT1-GOF (n=7) found that 57% seroconverted after two doses of vaccine [112]. Another case report on one individual with XMEN/MAGT1 deficiency reported a reactive spike-specific total antibody response after two doses of mRNA vaccine [90]. In addition, Timothy et al also completed a retrospective chart review of eight patients with CTLA-4 deficiency (two children and six adults).…”

An Overview of the Strategies to Boost SARS-CoV-2-Specific Immunity in People with Inborn Errors of Immunity

“…This is important because otherwise, known age-related changes in the immune system would confound the results of each study. The published study designs varied from observational [ 74 , 80 , 86 , 87 , 88 , 89 , 90 , 91 , 92 , 93 , 94 , 95 , 96 , 97 , 98 , 99 , 100 ] to interventional studies and clinical trials [ 83 , 85 , 86 , 101 , 102 ]. Furthermore, humoral responses were reported according to seroconversion, antibody concentration/titers, and, in some cases, virus neutralization/pseudo-neutralization capacity ( Figure 3 and Table 1 ).…”