Table_2_Immune Profile and Clinical Outcome of Breakthrough Cases After Vaccination With an Inactivated SARS-CoV-2 Vaccine.docx

Constant efforts to prevent infections by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are actively carried out around the world. Several vaccines are currently approved for emergency use in the population, while ongoing studies continue to provide information on their safety and effectiveness. CoronaVac is an inactivated SARS-CoV-2 vaccine with a good safety and immunogenicity profile as seen in phase 1, 2, and 3 clinical trials around the world, with an effectiveness of 65.9% for symptomatic cases. Although vaccination reduces the risk of disease, infections can still occur during or after completion of the vaccination schedule (breakthrough cases). This report describes the clinical and immunological profile of vaccine breakthrough cases reported in a clinical trial in progress in Chile that is evaluating the safety, immunogenicity, and efficacy of two vaccination schedules of CoronaVac (clinicaltrials.gov NCT04651790). Out of the 2,263 fully vaccinated subjects, at end of June 2021, 45 have reported symptomatic SARS-CoV-2 infection 14 or more days after the second dose (1.99% of fully vaccinated subjects). Of the 45 breakthrough cases, 96% developed mild disease; one case developed a moderate disease; and one developed a severe disease and required mechanical ventilation. Both cases that developed moderate and severe disease were adults over 60 years old and presented comorbidities. The immune response before and after SARS-CoV-2 infection was analyzed in nine vaccine breakthrough cases, revealing that six of them exhibited circulating anti-S1-RBD IgG antibodies with neutralizing capacities after immunization, which showed a significant increase 2 and 4 weeks after symptoms onset. Two cases exhibited low circulating anti-S1-RBD IgG and almost non-existing neutralizing capacity after either vaccination or infection, although they developed a mild disease. An increase in the number of interferon-γ-secreting T cells specific for SARS-CoV-2 was detected 2 weeks after the second dose in seven cases and after symptoms onset. In conclusion, breakthrough cases were mostly mild and did not necessarily correlate with a lack of vaccine-induced immunity, suggesting that other factors, to be defined in future studies, could lead to symptomatic infection after vaccination with CoronaVac.

全球范围内正持续开展针对严重急性呼吸综合征冠状病毒2（severe acute respiratory syndrome coronavirus 2, SARS-CoV-2）感染的防控工作。目前已有多款疫苗获批用于人群紧急使用，相关后续研究仍在持续补充其安全性与有效性的临床数据。CoronaVac是一款灭活型SARS-CoV-2疫苗，其安全性与免疫原性已在全球范围内的I、II、III期临床试验中得到验证，对有症状感染的保护效力为65.9%。尽管疫苗接种可降低发病风险，但在接种程序完成期间或完成后，仍可能发生感染（即突破感染病例，breakthrough cases）。本报告描述了智利一项正在进行的临床试验中报告的疫苗突破感染病例的临床与免疫学特征，该试验旨在评估CoronaVac两种接种程序的安全性、免疫原性与保护效力，试验注册号为clinicaltrials.gov NCT04651790。截至2021年6月末，在2263名完成全程接种的受试者中，有45名在第二剂接种14天及以上后出现有症状的SARS-CoV-2感染，占全程接种受试者的1.99%。在这45例突破感染病例中，96%表现为轻症，1例为中症，另有1例为重症并需要机械通气。出现中症与重症的两名受试者均为60岁以上老年人，且合并基础疾病。研究人员对9例突破感染病例在感染前后的免疫应答进行了分析，结果显示其中6例在完成疫苗接种后，体内已存在具有中和活性的循环抗S1-RBD IgG抗体，且在症状出现后2周和4周，该抗体水平显著升高。另有2例受试者在完成疫苗接种或感染后，循环抗S1-RBD IgG水平较低，中和活性几乎缺失，但仍出现了轻症感染。在7例受试者中，研究人员在第二剂接种后2周检测到针对SARS-CoV-2的分泌干扰素-γ的特异性T细胞数量增加，且在症状出现后该细胞群体进一步扩增。综上，疫苗突破感染病例多为轻症，且未必与疫苗诱导的免疫应答不足相关，这提示未来研究需明确其他潜在因素，这些因素可能导致CoronaVac接种后出现有症状感染。