PDF(Pubmed)
Abstract：
Despite the robust immunogenicity of SARS-CoV-2 mRNA vaccines, emerging data have revealed enhanced neutralizing antibody and T cell cross-reactivity among individuals that previously experienced COVID-19, pointing to a hybrid immune advantage with infection-associated immune priming. Beyond neutralizing antibodies and T cell immunity, mounting data point to a potential role for additional antibody effector functions, including opsinophagocytic activity, in the resolution of symptomatic COVID-19. Whether hybrid immunity modifies the Fc-effector profile of the mRNA vaccine-induced immune response remains incompletely understood. Thus, here we profiled the SARS-CoV-2 specific humoral immune response in a group of individuals with and without prior COVID-19. As expected, hybrid Spike-specific antibody titers were enhanced following the primary dose of the mRNA vaccine but were similar to those achieved by naive vaccinees after the second mRNA vaccine dose. Conversely, Spike-specific vaccine-induced Fc-receptor binding antibody levels were higher after the primary immunization in individuals with prior COVID-19 and remained higher following the second dose compared to those in naive individuals, suggestive of a selective improvement in the quality, rather than the quantity, of the hybrid humoral immune response. Thus, while the magnitude of antibody titers alone may suggest that any two antigen exposures-either hybrid immunity or two doses of vaccine alone-represent a comparable prime/boost immunologic education, we find that hybrid immunity offers a qualitatively improved antibody response able to better leverage Fc-effector functions against conserved regions of the virus. IMPORTANCE Recent data indicates improved immunity to SARS-CoV-2 in individuals who experience a combination of two mRNA vaccine doses and infection, \"hybrid immunity,\" compared to individuals who receive vaccination or experience infection alone. While previous infection accelerates the vaccine-induced immune response following the first dose of mRNA vaccination, subsequent doses demonstrate negligible increases in antibody titers or T cell immunity. Here, using systems serology, we observed a unique antibody profile induced by hybrid immunity, marked by the unique induction of robust Fc-recruiting antibodies directed at the conserved region of the viral Spike antigen, the S2-domain, induced at lower levels in individuals who only received mRNA vaccination. Thus, hybrid immunity clearly redirects vaccine-induced immunodominance, resulting in the induction of a robust functional humoral immune response to the most highly conserved region of the SARS-CoV-2 Spike antigen, which may be key to protection against existing and emerging variants of concern. Thus, next-generation vaccines able to mimic hybrid immunity and drive a balanced response to conserved regions of the Spike antigen may confer enhanced protection against disease.
摘要：
尽管SARS-CoV-2mRNA疫苗具有强大的免疫原性，新出现的数据显示，以前经历过COVID-19的个体中和抗体和T细胞交叉反应性增强，这表明与感染相关的免疫引发具有混合免疫优势。除了中和抗体和T细胞免疫，越来越多的数据指向额外的抗体效应子功能的潜在作用，包括吞噬作用，在有症状的COVID-19的解决中。杂合免疫是否修饰mRNA疫苗诱导的免疫应答的Fc效应谱仍未完全了解。因此，在这里，我们分析了一组既往有和没有COVID-19的个体的SARS-CoV-2特异性体液免疫反应。不出所料,在mRNA疫苗的主要剂量后,杂种Spike特异性抗体滴度增强,但与首次接种mRNA疫苗的首次接种者相似.相反，在初次免疫接种之前患有COVID-19的个体中，刺突特异性疫苗诱导的Fc受体结合抗体水平较高，在第二次接种后与未接受治疗的个体相比仍然较高，暗示质量的选择性改进，而不是数量，杂种体液免疫反应。因此，而单独的抗体滴度的大小可能表明，任何两种抗原暴露——无论是混合免疫还是单独的两剂疫苗——代表了相当的免疫教育。我们发现,杂交免疫提供了质量上改善的抗体应答,能够更好地利用针对病毒保守区的Fc效应子功能.重要性最近的数据表明，经历两种mRNA疫苗剂量和感染的个体对SARS-CoV-2的免疫力提高，“混合免疫，“与接受疫苗接种或单独经历感染的个体相比。虽然先前的感染在第一剂mRNA疫苗接种后加速了疫苗诱导的免疫反应，随后的剂量显示抗体滴度或T细胞免疫的增加可忽略不计.这里,使用系统血清学，我们观察到杂合免疫诱导的独特抗体谱，以针对病毒尖峰抗原保守区的强大Fc募集抗体的独特诱导为标志，S2域，在仅接受mRNA疫苗接种的个体中以较低的水平诱导。因此，混合免疫清楚地重定向疫苗诱导的免疫优势，导致对SARS-CoV-2尖峰抗原最高度保守区域的强大功能性体液免疫应答的诱导，这可能是保护免受现有和新出现的关注变体的关键。因此，能够模拟混合免疫并驱动对Spike抗原保守区域的平衡反应的下一代疫苗可能会增强对疾病的保护作用.
