Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Center, Seattle, WA, USA.
Public Health Sciences Division, Fred Hutchinson Cancer Center, Seattle, WA, USA.
Nat Commun. 2024 Nov 12;15(1):9785. doi: 10.1038/s41467-024-53727-y.
Assessment of immune correlates of severe COVID-19 has been hampered by the low numbers of severe cases in COVID-19 vaccine efficacy (VE) trials. We assess neutralizing and binding antibody levels at 4 weeks post-Ad26.COV2.S vaccination as correlates of risk and of protection against severe-critical COVID-19 through 220 days post-vaccination in the ENSEMBLE trial (NCT04505722), constituting ~4.5 months longer follow-up than our previous correlates analysis and enabling inclusion of 42 severe-critical vaccine-breakthrough cases. Neutralizing antibody titer is a strong inverse correlate of severe-critical COVID-19, with estimated hazard ratio (HR) per 10-fold increase 0.35 (95% CI: 0.13, 0.90). In a multivariable model, HRs are 0.31 (0.11, 0.89) for neutralizing antibody titer and 1.22 (0.49, 3.02) for anti-Spike binding antibody concentration. VE against severe-critical COVID-19 rises with neutralizing antibody titer: 63.1% (95% CI: 40.0%, 77.3%) at unquantifiable [<4.8975 International Units (IU)50/ml], 85.2% (47.2%, 95.3%) at just-quantifiable (5.2 IU50/ml), and 95.1% (81.1%, 96.9%) at 90 percentile (30.2 IU50/ml). At the same titers, VE against moderate COVID-19 is 32.5% (11.8%, 48.4%), 33.9% (19.1%, 59.3%), and 60.7% (40.4%, 76.4%). Protection against moderate vs. severe disease may require higher antibody levels, and very low antibody levels and/or other immune responses may associate with protection against severe disease.
评估 COVID-19 重症病例的免疫相关性一直受到 COVID-19 疫苗有效性 (VE) 试验中重症病例数量较少的阻碍。我们评估了 Ad26.COV2.S 接种后 4 周时的中和抗体和结合抗体水平，作为风险和预防接种后 220 天内重症-危重症 COVID-19 的保护相关因素，与我们之前的相关性分析相比，随访时间延长了约 4.5 个月，从而纳入了 42 例重症突破病例。中和抗体滴度与重症-危重症 COVID-19 呈强负相关，每增加 10 倍的估计危险比 (HR) 为 0.35（95%CI：0.13，0.90）。在多变量模型中，中和抗体滴度的 HR 为 0.31（0.11，0.89），抗 Spike 结合抗体浓度的 HR 为 1.22（0.49，3.02）。针对重症-危重症 COVID-19 的 VE 随着中和抗体滴度的升高而升高：未定量 [<4.8975 国际单位 (IU)50/ml] 时为 63.1%（95%CI：40.0%，77.3%），刚好可定量（5.2IU50/ml）时为 85.2%（47.2%，95.3%），达到 90 百分位（30.2IU50/ml）时为 95.1%（81.1%，96.9%）。在相同滴度时，针对中度 COVID-19 的 VE 为 32.5%（11.8%，48.4%）、33.9%（19.1%，59.3%）和 60.7%（40.4%，76.4%）。预防中度与重度疾病可能需要更高的抗体水平，而非常低的抗体水平和/或其他免疫反应可能与预防重症疾病相关。
