Zhang Guangxu, Wang Qian, Ji Kai, Wang Yuanzhou, Xu Wei, Zhou Jie, Liu Zezhong, Xiu Ruixue, Xing Lixiao, Zhou Jianghao, Shi Yuren, Lu Xishan, Wang Xuanyi, Ying Bo, Lu Lu, Jiang Shibo
Key Laboratory of Medical Molecular Virology (Ministry of Education/National Health Commission/Chinese Academy of Medical Science), Shanghai Institute of Infectious Disease and Biosecurity, School of Basic Medical Sciences Fudan University Shanghai China.
Suzhou Abogen Biosciences Co., Ltd. Suzhou Jiangsu China.
MedComm (2020). 2025 Jul 7;6(7):e70273. doi: 10.1002/mco2.70273. eCollection 2025 Jul.
Original antigenic sin (OAS), or immune imprinting, triggered by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) ancestral (WT) strain vaccine, or infection, has led to weakened neutralizing antibody response against Omicron variant like BA.2 and subvariant like XBB. This calls for the development of an innovative booster vaccine, or vaccination strategy, that will eliminate, or attenuate, OAS, thus, enhancing broad-neutralizing antibody (bnAb) response. Accordingly, we herein proposed a leveraged vaccination strategy to counter the OAS effect by controlling the antigenic distance of booster vaccine and increasing boost vaccination frequency. We found that prime with WT-RBD and boost with XBB-RBD resulted in significantly higher bnAb response against most Omicron subvariants tested than that after prime with WT-RBD and boost with BA.2-RBD because the antigenic distance between WT-RBD and XBB-RBD is much longer than that between WT-RBD and BA.2-RBD. An additional boost with XBB-RBD further enhanced bnAb response. These findings indicate that a leveraged vaccination approach based on antigenic distance could be effective in reducing OAS, thereby strengthening bnAb response against SARS-CoV-2 Omicron subvariants. As such, this vaccination strategy could be just as effective in combating other fast-evolving RNA viruses known for their high transmissibility and infectivity.
由严重急性呼吸综合征冠状病毒2（SARS-CoV-2）原始（野生型）毒株疫苗或感染引发的原始抗原性原罪（OAS），即免疫印记，导致针对奥密克戎变种（如BA.2）和亚变种（如XBB）的中和抗体反应减弱。这就需要开发一种创新的加强疫苗或接种策略，以消除或减弱OAS，从而增强广泛中和抗体（bnAb）反应。因此，我们在此提出一种优化的接种策略，通过控制加强疫苗的抗原距离并增加加强接种频率来对抗OAS效应。我们发现，用野生型受体结合域（WT-RBD）进行初次免疫，并用XBB-RBD进行加强免疫，与用野生型受体结合域进行初次免疫并用BA.2-RBD进行加强免疫相比，对大多数测试的奥密克戎亚变种产生的bnAb反应显著更高，因为野生型受体结合域与XBB-RBD之间的抗原距离比野生型受体结合域与BA.2-RBD之间的抗原距离长得多。用XBB-RBD进行额外的加强免疫进一步增强了bnAb反应。这些发现表明，基于抗原距离的优化接种方法可能有效降低OAS，从而增强针对SARS-CoV-2奥密克戎亚变种的bnAb反应。因此，这种接种策略在对抗其他以高传播性和感染性著称的快速进化RNA病毒方面可能同样有效。
