Infection Prevention & Control Unit, Sheba Medical Center, Ramat Gan, Israel; Sackler School of Medicine, Tel-Aviv University, Tel Aviv, Israel.
Sackler School of Medicine, Tel-Aviv University, Tel Aviv, Israel; Central Virology Laboratory, Public Health Services, Ministry of Health, Ramat Gan, Israel.
Lancet Microbe. 2023 May;4(5):e309-e318. doi: 10.1016/S2666-5247(23)00012-5. Epub 2023 Mar 21.
Identifying COVID-19 correlates of protection and immunity thresholds is important for policy makers and vaccine development. We aimed to identify correlates of protection of BNT162b2 (Pfizer-BioNTech) vaccination against COVID-19.
In this prospective cohort study, households within a radius of 40 km of the Sheba Medical Center in Israel in which a new SARS-CoV-2 infection (defined as the index case) was detected within the previous 24 h were approached between July 25 and Nov 15, 2021. We included adults (aged >18 years) who had received one or two vaccine doses, had an initial negative SARS-CoV-2 PCR and no previous infection reported, and had a valid IgG and neutralising antibody result. The exposure of interest was baseline immune status, including IgG antibody concentration, neutralising antibody titre, and T-cell activation. The outcomes of interest were PCR-positive SARS-CoV-2 infection between day 2 and day 21 of follow-up and intensity of disease symptoms (self-reported via a telephone questionnaire) among participants who had a confirmed infection. Multivariable logistic and ordered logit ordinal regressions were used for the adjusted analysis. To identify immunological thresholds for clinical protection, we estimated the conditional probability of infection and moderate or severe disease for individuals with pre-exposure IgG and neutralising antibody concentrations above each value observed in the study data.
From 16 675 detected index cases in the study region, 5718 household members agreed to participate, 1461 of whom were eligible to be included in our study. 333 (22·8%) of 1461 household members who were not infected with SARS-CoV-2 at baseline were infected within 21 days of follow-up. The baseline (pre-exposure) IgG and neutralising antibodies were higher in participants who remained uninfected than in those who became infected (geometric mean IgG antibody concentration 168·2 binding antibody units [BAU] per mL [95% CI 158·3-178·7] vs 130·5 BAU/mL [118·3-143·8] and geometric mean neutralising antibody titre 197·5 [181·9-214·4] vs 136 ·7 [120·3-155·4]). Increasing IgG and neutralising antibody concentrations were also significantly associated with a reduced probability of increasing disease severity. Odds of infection were significantly reduced each time baseline IgG antibody concentration increased by a factor of ten (odds ratio [OR] 0·43 [95% CI 0·26-0·70]) and each time baseline neutralising antibody titre increased by a factor of two (0·82 [0·74-0·92]). In our cohort, the probability of infection if IgG antibody concentrations were higher than 500 BAU/mL was 11% and the probability of moderate disease severity was 1%; the probability of infection if neutralising antibody titres were above or equal to 1024 was 8% and the probability of moderate disease severity was 2%. T-cell activation rates were not significantly associated with reduced probability of infection (OR 1·04, 95% CI 0·83-1·30).
Both IgG and neutralising antibodies are correlates of protection against SARS-CoV-2 infection. Our data suggest that IgG concentrations higher than 500 BAU/mL and neutralising antibody titres of 1024 or more are thresholds for immunological protection from SARS-CoV-2 delta variant infection. Potentially, updated protective thresholds against emerging variants of concern could be calculated, which could support decision makers on administration of new vaccination strategies and on the optimal period between vaccine doses.
Israeli Ministry of Health.
确定 COVID-19 的保护和免疫阈值相关因素对于政策制定者和疫苗开发至关重要。我们旨在确定 BNT162b2（辉瑞-生物科技）疫苗接种对 COVID-19 的保护相关因素。
在这项前瞻性队列研究中，在以色列谢巴医疗中心半径 40 公里范围内，如果在过去 24 小时内发现新的 SARS-CoV-2 感染（定义为索引病例），则在 2021 年 7 月 25 日至 11 月 15 日期间与家庭接触。我们纳入了成年人（年龄大于 18 岁），他们已接种一剂或两剂疫苗，最初 SARS-CoV-2 PCR 检测结果为阴性，且未报告之前感染，并且 IgG 和中和抗体检测结果有效。感兴趣的暴露因素为基线免疫状态，包括 IgG 抗体浓度、中和抗体滴度和 T 细胞激活。感兴趣的结局为随访第 2 天至第 21 天 PCR 阳性 SARS-CoV-2 感染和参与者确诊感染后的疾病症状严重程度（通过电话问卷调查报告）。多变量逻辑回归和有序逻辑回归用于调整分析。为了确定临床保护的免疫学阈值，我们估计了个体在研究数据中观察到的 IgG 和中和抗体浓度之上的个体感染和中度或重度疾病的概率。
在研究区域检测到的 16675 例索引病例中，有 5718 个家庭同意参与，其中 1461 个符合纳入我们研究的条件。在基线未感染 SARS-CoV-2 的 333（22.8%）名未感染者中，有 333 人在随访 21 天内感染。与未感染者相比，未感染者的基线（暴露前）IgG 和中和抗体水平更高（几何平均 IgG 抗体浓度为 168.2 结合抗体单位/毫升[95%CI 158.3-178.7]比 130.5 BAU/mL[118.3-143.8]和几何平均中和抗体滴度 197.5[181.9-214.4]比 136.7[120.3-155.4]）。IgG 和中和抗体浓度的增加也与疾病严重程度增加的概率降低显著相关。每次基线 IgG 抗体浓度增加十倍（比值比[OR]0.43[95%CI 0.26-0.70]）和每次基线中和抗体滴度增加两倍（0.82[0.74-0.92]），感染的可能性显著降低。在我们的队列中，如果 IgG 抗体浓度高于 500 BAU/mL，则感染的概率为 11%，中度疾病严重程度的概率为 1%；如果中和抗体滴度高于或等于 1024，则感染的概率为 8%，中度疾病严重程度的概率为 2%。T 细胞激活率与感染概率降低无显著相关性（OR 1.04，95%CI 0.83-1.30）。
IgG 和中和抗体都是对 SARS-CoV-2 感染的保护相关因素。我们的数据表明，IgG 浓度高于 500 BAU/mL 和中和抗体滴度为 1024 或更高是对 SARS-CoV-2 德尔塔变异体感染免疫保护的阈值。可能可以计算出针对新出现的关注变异体的更新保护阈值，这将支持决策者制定新的疫苗接种策略和疫苗接种剂量之间的最佳间隔。
以色列卫生部。
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