Fathi Parinaz, Alfonso Andrea Lucia, Yek Christina, Putman Zoe, Drew Matthew, Esposito Dominic, Zaidi Irfan, Chea Sophana, Ly Sokna, Sath Rathanak, Lon Chanthap, Chea Huch, Leang Rithea, Huy Rekol, Ly Sovann, Seng Heng, Tan Chee Wah, Zhu Feng, Wang Lin-Fa, Oliveira Fabiano, Sadtler Kaitlyn, Manning Jessica
Section on Immunoengineering, Biomedical Engineering and Technology Acceleration Center, National Institute of Biomedical Imaging and Bioengineering, Bethesda, MD, 20892, USA.
Laboratory of Malaria and Vector Research, National Institute of Allergy and Infectious Diseases, Rockville, MD, 20892, USA.
Adv Sci (Weinh). 2025 Jan;12(1):e2403503. doi: 10.1002/advs.202403503. Epub 2024 Oct 29.
Dynamic pathogen exposure may impact the immunological response to SARS-CoV-2 (SCV2). One potential explanation for the lack of severe SCV2-related morbidity and mortality in Southeast Asia is prior exposure to related betacoronaviruses. Recent discoveries of SCV2-related betacoronaviruses from horseshoe bats (Rhinolophus sinicus) in Thailand, Laos, and Cambodia suggest the potential for bat-to-human spillover exposures in the region. In this work, serum antibodies to protein constructs from SCV2 and a representative bat coronavirus isolated in Cambodia (RshSTT182) are measured in pre-pandemic Cambodian human sera using ELISA assays. Of 293 Cambodian samples tested (N = 131 with acute malaria, n = 162 with acute undifferentiated febrile illness), 32 (10.9%) are seropositive for SCV2 based on established Spike and receptor-binding domain (RBD) cutoffs. Within SCV2 seropositive samples, 16 (50%) have higher antibody levels to antigens from the representative virus RshSTT182 versus SCV2 antigens; competitive binding ELISA assays demonstrate inhibition of reactivity to SCV2 Spike after pre-incubation with RshSTT182 Spike. Surrogate virus neutralization tests demonstrate that 8/30 (26.7%) SCV2 ELISA positive pre-pandemic Cambodian samples have neutralizing activity against SCV2, while 14/30 (46.7%) have activity against other SCV2-related betacoronaviruses. These data suggest that exposure to related betacoronaviruses may elicit cross-reactive immunity to SCV2 prior to the global pandemic.
动态病原体暴露可能会影响对严重急性呼吸综合征冠状病毒2（SARS-CoV-2，简称SCV2）的免疫反应。东南亚地区缺乏与SCV2相关的严重发病和死亡情况的一个潜在解释是先前接触过相关的β冠状病毒。最近在泰国、老挝和柬埔寨从菊头蝠（中华菊头蝠）中发现了与SCV2相关的β冠状病毒，这表明该地区存在蝙蝠向人类溢出传播的可能性。在这项研究中，使用酶联免疫吸附测定（ELISA）方法，在柬埔寨疫情前的人类血清中检测针对SCV2和在柬埔寨分离出的一种代表性蝙蝠冠状病毒（RshSTT182）蛋白构建体的血清抗体。在检测的293份柬埔寨样本中（131份患有急性疟疾，162份患有急性未分化发热性疾病），根据既定的刺突蛋白（Spike）和受体结合域（RBD）临界值，32份（10.9%）样本对SCV2呈血清学阳性。在SCV2血清学阳性样本中，16份（50%）对代表性病毒RshSTT182抗原的抗体水平高于对SCV2抗原的抗体水平；竞争性结合ELISA试验表明，用RshSTT182刺突蛋白预孵育后，对SCV2刺突蛋白的反应性受到抑制。替代病毒中和试验表明，30份疫情前ELISA检测为阳性的柬埔寨样本中有8份（26.7%）对SCV2具有中和活性，而14份（46.7%）对其他与SCV2相关的β冠状病毒具有活性。这些数据表明，在全球大流行之前，接触相关的β冠状病毒可能会引发对SCV2的交叉反应性免疫。
