Office of Vaccines Research and Review, Center for Biologics Evaluation and Research, US Food and Drug Administration, Silver Spring, Maryland, USA.
Viral Epidemiology and Immunity Unit, Laboratory of Infectious Diseases, Division of Intramural Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, USA.
J Virol. 2024 Nov 19;98(11):e0094824. doi: 10.1128/jvi.00948-24. Epub 2024 Oct 4.
Antigenic assessments of SARS-CoV-2 variants inform decisions to update COVID-19 vaccines. Primary infection sera are often used for assessments, but such sera are rare due to population immunity from SARS-CoV-2 infections and COVID-19 vaccinations. Here, we show that neutralization titers and breadth of matched human and hamster pre-Omicron variant primary infection sera correlate well and generate similar antigenic maps. The hamster antigenic map shows modest antigenic drift among XBB sub-lineage variants, with JN.1 and BA.4/BA.5 variants within the XBB cluster, but with fivefold to sixfold antigenic differences between these variants and XBB.1.5. Compared to sera following only ancestral or bivalent COVID-19 vaccinations, or with post-vaccination infections, XBB.1.5 booster sera had the broadest neutralization against XBB sub-lineage variants, although a fivefold titer difference was still observed between JN.1 and XBB.1.5 variants. These findings suggest that antibody coverage of antigenically divergent JN.1 could be improved with a matched vaccine antigen.IMPORTANCEUpdates to COVID-19 vaccine antigens depend on assessing how much vaccine antigens differ antigenically from newer SARS-CoV-2 variants. Human sera from single variant infections are ideal for discriminating antigenic differences among variants, but such primary infection sera are now rare due to high population immunity. It remains unclear whether sera from experimentally infected animals could substitute for human sera for antigenic assessments. This report shows that neutralization titers of variant-matched human and hamster primary infection sera correlate well and recognize variants similarly, indicating that hamster sera can be a proxy for human sera for antigenic assessments. We further show that human sera following an XBB.1.5 booster vaccine broadly neutralized XBB sub-lineage variants but titers were fivefold lower against the more recent JN.1 variant. These findings support updating the current COVID-19 vaccine variant composition and developing a framework for assessing antigenic differences in future variants using hamster primary infection sera.
SARS-CoV-2 变体的抗原评估为更新 COVID-19 疫苗提供了依据。通常使用初次感染血清进行评估，但由于 SARS-CoV-2 感染和 COVID-19 疫苗接种导致人群免疫，初次感染血清非常罕见。在这里，我们表明，匹配的人类和仓鼠感染前奥密克戎变体的中和滴度和广度与原始血清相关良好，并产生相似的抗原图谱。仓鼠的抗原图谱显示，在 XBB 亚谱系变体中存在适度的抗原漂移，其中 JN.1 和 BA.4/BA.5 变体在 XBB 簇内，但这些变体与 XBB.1.5 之间存在五倍至六倍的抗原差异。与仅接受原始或二价 COVID-19 疫苗接种或接种后感染的血清相比，XBB.1.5 加强血清对 XBB 亚谱系变体的中和作用最广泛，尽管 JN.1 和 XBB.1.5 变体之间仍存在五倍的滴度差异。这些发现表明，用匹配的疫苗抗原可以提高对抗原上有差异的 JN.1 的抗体覆盖。
重要性 COVID-19 疫苗抗原的更新取决于评估疫苗抗原在多大程度上与新型 SARS-CoV-2 变体在抗原上有所不同。来自单一变体感染的人类血清是区分变体之间抗原差异的理想选择，但由于人群免疫力高，现在这种初次感染血清非常罕见。目前尚不清楚实验感染动物的血清是否可以替代人类血清进行抗原评估。本报告表明，匹配的人类和仓鼠感染前血清的中和滴度相关性良好，并且能够相似地识别变体，表明仓鼠血清可以作为人类血清的替代品用于抗原评估。我们进一步表明，接种 XBB.1.5 加强疫苗后的人类血清广泛中和 XBB 亚谱系变体，但对最近的 JN.1 变体的滴度低五倍。这些发现支持更新当前 COVID-19 疫苗变体组成，并开发使用仓鼠感染前血清评估未来变体抗原差异的框架。
