Lichtenegger Sabine, Sonnleitner Sissy Therese, Saiger Sabine, Zauner Andrea, Hardt Melina, Kleinhappl Barbara, Wagner Gabriel E, Steinmetz Ivo
Diagnostic & Research Institute of Hygiene, Microbiology and Environmental Medicine, Diagnostic and Research Center for Molecular Biomedicine, Medical University of Graz, Graz, Austria.
Diagnostic & Research Institute of Pathology, Diagnostic and Research Center for Molecular Biomedicine, Medical University of Graz, Graz, Austria.
Microbiol Spectr. 2025 Apr 8;13(5):e0214824. doi: 10.1128/spectrum.02148-24.
A large number of studies have demonstrated that anti-receptor-binding domain (RBD)-binding antibody titers correlate with SARS-CoV-2 neutralization and protection from the disease. Unlike live virus neutralization assays, antibody-binding assays are easier to perform, require lower biosafety levels, and have therefore served as a substitute for virus neutralization assays throughout the SARS-CoV-2 pandemic. Although anti-RBD antibodies are usually neutralizing, there is evidence that they can also be non-neutralizing. Moreover, different immunization regimens can vary in the induction of SARS-CoV-2-neutralizing antibodies. In this study, we hypothesized that sera from individuals with different immunization and infection histories, but with the same amount of anti-RBD total immunoglobulin, differ in their neutralizing potency. A total of 27 sera from SARS-CoV-2 convalescent, vaccinated individuals, and 27 vaccinated-only individuals were investigated by using a widely used antibody-binding assay (Elecsys anti-SARS-CoV-2 S enzyme-linked immunosorbent assay [ELISA]) and a live virus neutralization assay. As expected, anti-RBD immunoglobulin units correlated with virus neutralization capacity within the vaccine and hybrid immunized group. However, sera from both groups with matched anti-RBD units varied significantly in their neutralization potential. In detail, our data indicate a significantly higher neutralization potency of hybrid immunity compared to vaccinated-only sera with similar anti-RBD immunoglobulin levels. Our study highlights the need for cautious interpretation of quantitative antibody data from anti-RBD ELISAs, especially when comparing differently immunized groups. In other words, very similar anti-RBD levels can show very different functional activity. This finding has implications for determining possible future correlates of protection.
Throughout the SARS-CoV-2 pandemic, neutralizing antibody levels have been central to predict a protective immune response. Anti-receptor-binding domain (RBD) enzyme-linked immunosorbent assays (ELISAs) correlate with neutralization assays and are due to the integration of simple performance with timely results used as surrogate assays. However, previous studies determining correlation used homogeneous cohorts. We reevaluated the correlation of a frequently used anti-RBD ELISA and a live virus neutralization assay using a heterogeneous cohort consisting of a vaccinated group without prior SARS-CoV-2 infection and a vaccinated convalescent group. The neutralizing capacity of sera with matched anti-RBD units significantly differed between groups, decreasing the correlation of the assays. Our findings highlight the necessity of considering the immunization context when interpreting serological tests and suggest that different immunization groups may require distinct protective thresholds. Considering the immunization history, we can develop more accurate predictions of immunity not only for SARS-CoV-2 but also for future challenges.
大量研究表明，抗受体结合域（RBD）结合抗体滴度与SARS-CoV-2中和及疾病防护相关。与活病毒中和试验不同，抗体结合试验操作更简便，所需生物安全水平更低，因此在整个SARS-CoV-2大流行期间一直作为病毒中和试验的替代方法。虽然抗RBD抗体通常具有中和作用，但有证据表明它们也可能是非中和性的。此外，不同的免疫方案在诱导SARS-CoV-2中和抗体方面可能存在差异。在本研究中，我们假设具有不同免疫和感染史但抗RBD总免疫球蛋白量相同的个体血清，其中和效力存在差异。通过使用一种广泛应用的抗体结合试验（Elecsys抗SARS-CoV-2 S酶联免疫吸附测定[ELISA]）和活病毒中和试验，对27份来自SARS-CoV-2康复者、接种疫苗者的血清以及27份仅接种疫苗者的血清进行了研究。正如预期的那样，抗RBD免疫球蛋白单位与疫苗接种组和混合免疫组内的病毒中和能力相关。然而，两组抗RBD单位匹配的血清在中和潜力上存在显著差异。具体而言，我们的数据表明，与抗RBD免疫球蛋白水平相似的仅接种疫苗血清相比，混合免疫的中和效力显著更高。我们的研究强调，在解释抗RBD ELISA的定量抗体数据时需要谨慎，尤其是在比较不同免疫组时。换句话说，非常相似的抗RBD水平可能显示出非常不同的功能活性。这一发现对确定未来可能的保护相关性具有重要意义。
在整个SARS-CoV-2大流行期间，中和抗体水平一直是预测保护性免疫反应的核心。抗受体结合域（RBD）酶联免疫吸附测定（ELISA）与中和试验相关，由于其操作简便且结果及时，被用作替代试验。然而，以往确定相关性的研究使用的是同质队列。我们使用一个由未感染过SARS-CoV-2的接种疫苗组和接种疫苗的康复组组成的异质队列，重新评估了一种常用的抗RBD ELISA与活病毒中和试验之间的相关性。抗RBD单位匹配的血清中和能力在两组之间存在显著差异，降低了试验之间的相关性。我们的研究结果强调了在解释血清学检测时考虑免疫背景的必要性，并表明不同的免疫组可能需要不同的保护阈值。考虑免疫史，我们不仅可以对SARS-CoV-2，而且可以对未来的挑战做出更准确的免疫预测。
