Roederer Alex L, Cao Yi, Li Chia Jung, Lim Eunice, Canaday David H, Gravenstein Stefan, Balazs Alejandro B
Ragon Institute of MGH, MIT, and Harvard, Cambridge, MA, 02139, USA.
Case Western Reserve University School of Medicine, Cleveland, OH.
medRxiv. 2025 Mar 5:2025.03.01.25323010. doi: 10.1101/2025.03.01.25323010.
Studies have demonstrated that repeated mRNA vaccination enhances the breadth of neutralization against diverse SARS-CoV-2 variants. However, the development of antibodies capable of neutralizing across the Coronavirinae subfamily is poorly understood. In this study, we analyze serum samples to determine their neutralization breadth and potency and identify their antigenic targets. Using a cohort of older individuals and healthcare workers, we track correlates of broad neutralizing responses, including fusion peptide (FP) antibody elicitation. We find that although broadly neutralizing responses are often a result of RBD-specific antibodies, a rare subset of donors produce FP-specific broadly neutralizing responses. Interestingly, FP-specific antibodies are not observed in COVID-naive individuals irrespective of vaccination regimen, but rather, they occur following natural infection or vaccine breakthrough. This study highlights the epitope targets underpinning broadly neutralizing antibody responses to coronaviruses and suggests that existing vaccines are insufficient to promote the elicitation of FP-directed broadly neutralizing coronavirus antibodies.
研究表明，重复进行mRNA疫苗接种可增强针对多种严重急性呼吸综合征冠状病毒2（SARS-CoV-2）变体的中和广度。然而，对于能够中和整个冠状病毒亚科的抗体的产生，我们了解得还很少。在本研究中，我们分析血清样本以确定其中和广度和效力，并确定其抗原靶点。我们利用一组老年人和医护人员，追踪广泛中和反应的相关因素，包括融合肽（FP）抗体的诱导情况。我们发现，虽然广泛中和反应通常是由受体结合域（RBD）特异性抗体引起的，但有一小部分供体产生了FP特异性的广泛中和反应。有趣的是，无论接种方案如何，在未感染过新冠病毒的个体中均未观察到FP特异性抗体，相反，它们是在自然感染或疫苗突破感染后出现的。这项研究突出了支持对冠状病毒产生广泛中和抗体反应的表位靶点，并表明现有疫苗不足以促进诱导针对FP的广泛中和冠状病毒抗体。
