Beeker Léopold, Obadia Thomas, Bloch Emma, Garcia Laura, Le Fol Manon, Charmet Tiffany, Arowas Laurence, Artus Rémy, Cheny Olivia, Cheval Dorian, Dahoumane Yanis, Delhaye Maurine, Ergen Delal, Essaidani Mariem, Fanaud Christine, Fernandes Pellerin Sandrine, Jolly Nathalie, Laude Hélène, Roux Emmanuel, Samson Marine, Sangari Linda, Ungeheuer Marie-Noëlle, Vacant Sophie, Zayoud Ayla, Donnadieu Françoise, Pelleau Stéphane, Galmiche Simon, Fontanet Arnaud, White Michael
Infectious Disease Epidemiology and Analytics G5 Unit, Department of Global Health, Institut Pasteur, Université Paris-Cité, Paris, France.
Emerging Diseases Epidemiology Unit, Department of Global Health, Institut Pasteur, Université Paris-Cité, Paris, France.
Open Forum Infect Dis. 2025 Jan 8;12(1):ofaf006. doi: 10.1093/ofid/ofaf006. eCollection 2025 Jan.
Establishing correlates of protection often requires large cohorts. A rapid and adaptable case-control study design can be used to identify antibody correlates of protection against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in serum and saliva.
We designed a case-control study to compare antibody levels between cases of SARS-CoV-2 infection within 5 days of symptom onset and uninfected controls. Controls were matched on age, number of coronavirus disease 2019 vaccine doses, time since last dose, and past episodes of infection. We quantified anti-SARS-CoV-2 and seasonal coronavirus immunoglobulin (Ig) G in serum and saliva at inclusion, 1 month, and 6 months.
We included 90 cases and 62 controls between February and September 2022. A boost and decay pattern of serum antibodies was observed in cases at 1 and 6 months, respectively, but not in controls. Anti-SARS-CoV-2 antibody levels were significantly higher in controls at inclusion both in serum (particularly antinucleocapsid IgG: 4.14 times higher compared with cases; 95% CI, 2.46-6.96) and saliva (particularly antispike for Delta variant IgG: 4.89 times higher compared with cases; 95% CI, 2.91-9.89). Saliva antibodies generally outperformed serum antibodies for case/control differentiation.
In this case-control study, we provided evidence of correlates of protection of anti-SARS-CoV-2 IgG in saliva and serum, with saliva antibodies often outperforming serum. The finding that antibodies in saliva are a better correlate of protection than antibodies in serum may inform vaccine development by highlighting the importance of robust induction of mucosal immune responses. This study design may be used during future epidemics for the prompt assessment of correlates of protection.
确定保护的相关因素通常需要大规模队列研究。一种快速且适应性强的病例对照研究设计可用于识别血清和唾液中针对严重急性呼吸综合征冠状病毒2（SARS-CoV-2）感染的抗体保护相关因素。
我们设计了一项病例对照研究，以比较症状出现后5天内SARS-CoV-2感染病例与未感染对照之间的抗体水平。对照在年龄、2019冠状病毒病疫苗接种剂量、最后一剂接种后的时间以及既往感染史方面进行匹配。我们在纳入时、1个月和6个月时对血清和唾液中的抗SARS-CoV-2和季节性冠状病毒免疫球蛋白（Ig）G进行了定量。
2022年2月至9月期间，我们纳入了90例病例和62例对照。病例在1个月和6个月时分别观察到血清抗体的增强和衰减模式，但对照中未观察到。纳入时，对照血清中的抗SARS-CoV-2抗体水平显著更高（特别是抗核衣壳IgG：比病例高4.14倍；95%置信区间，2.46 - 6.96），唾液中的抗SARS-CoV-2抗体水平也显著更高（特别是针对Delta变异株的抗刺突IgG：比病例高4.89倍；95%置信区间，2.91 - 9.89）。在区分病例/对照方面，唾液抗体通常优于血清抗体。
在这项病例对照研究中，我们提供了唾液和血清中抗SARS-CoV-2 IgG保护相关因素的证据，唾液抗体通常优于血清抗体。唾液中的抗体比血清中的抗体更能作为保护的相关因素这一发现，可能通过强调强大诱导黏膜免疫反应的重要性，为疫苗开发提供信息。这种研究设计可在未来疫情期间用于快速评估保护的相关因素。
