Department of Medicine, Washington University in St. Louis, St. Louis, MO 63110, USA.
Department of Pediatrics, Washington University in St. Louis, St. Louis, MO 63110, USA.
Cell Rep Med. 2022 Jun 21;3(6):100653. doi: 10.1016/j.xcrm.2022.100653. Epub 2022 Jun 9.
Individuals with primary antibody deficiency (PAD) syndromes have poor humoral immune responses requiring immunoglobulin replacement therapy. We followed individuals with PAD after severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccination by evaluating their immunoglobulin replacement products and serum for anti-spike binding, Fcγ receptor (FcγR) binding, and neutralizing activities. The immunoglobulin replacement products tested have low anti-spike and receptor-binding domain (RBD) titers and neutralizing activity. In coronavirus disease 2019 (COVID-19)-naive individuals with PAD, anti-spike and RBD titers increase after mRNA vaccination but wane by 90 days. Those vaccinated after SARS-CoV-2 infection develop higher and more sustained responses comparable with healthy donors. Most vaccinated individuals with PAD have serum-neutralizing antibody titers above an estimated correlate of protection against ancestral SARS-CoV-2 and Delta virus but not against Omicron virus, although this is improved by boosting. Thus, some immunoglobulin replacement products likely have limited protective activity, and immunization and boosting of individuals with PAD with mRNA vaccines should confer at least short-term immunity against SARS-CoV-2 variants, including Omicron.
原发性抗体缺陷（PAD）综合征患者的体液免疫反应较差，需要免疫球蛋白替代治疗。我们通过评估 PAD 个体接种严重急性呼吸综合征冠状病毒 2（SARS-CoV-2）后的免疫球蛋白替代产品和血清中的抗刺突结合、Fcγ 受体（FcγR）结合和中和活性来监测他们。测试的免疫球蛋白替代产品具有低的抗刺突和受体结合域（RBD）滴度和中和活性。在 COVID-19 原发性 PAD 个体中，mRNA 疫苗接种后抗刺突和 RBD 滴度增加，但在 90 天内下降。那些在 SARS-CoV-2 感染后接种疫苗的个体产生更高和更持久的反应，与健康供体相当。大多数接种疫苗的 PAD 个体的血清中和抗体滴度高于估计的对原始 SARS-CoV-2 和 Delta 病毒的保护相关性，但对奥密克戎病毒没有，尽管加强免疫可以改善这种情况。因此，一些免疫球蛋白替代产品可能具有有限的保护活性，用 mRNA 疫苗对 PAD 个体进行免疫接种和加强接种应该至少能在短期内提供针对 SARS-CoV-2 变体（包括奥密克戎）的免疫。
