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ORIGINAL RESEARCH article
Front. Immunol.
Sec. Vaccines and Molecular Therapeutics
Volume 16 - 2025 | doi: 10.3389/fimmu.2025.1543212
Chimeric receptor-binding domain vaccine design and sequential immunization enhanced broadly neutralizing antibody responses against COVID-19
Provisionally accepted
Xiao Yang 1 Xin Tang 1,2 Ying Sun 1 Hualong Xi 1 Wei Peng 3
Lu Yan 3 Wenjing Teng 1
Yang Zang 1*
Chunlai Jiang 1,2*- 1 Changchun BCHT Biotechnology Co.,Ltd., Changchun, China
- 2 National Engineering Laboratory of AIDS Vaccine, School of life science, Jilin University, Changchun, Jilin Province, China
- 3 The Medium Therapeutics Co., Ltd., Suzhou, China
Vaccines developed using modified messenger RNA (mRNA) technology show robust efficacy against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in humans. However, viral evolution in human and non-human hosts may compromise vaccine performance due to the emergence of new variants with strong immune-escape abilities. Therefore, a coronavirus disease 2019 (COVID-19) vaccine that induces high levels of broadly neutralizing antibodies (bnAbs) and responds quickly to viral mutations is urgently required. Here, we designed a bivalent mRNA vaccine, RBDco, based on the variant of concern (VOC) spike (S) protein receptor-binding domain (RBD) chimeric from different lineages fused with Fc fragments. In mice and non-human primates, RBDco effectively induced neutralizing antibodies against several pseudoviruses, including the possible epidemic variants XBB.1, XBB.1.9.1, and EA.1 pseudoviruses. In mice, RBDco induced bnAbs against 11 SARS-CoV-2 variant pseudoviruses from different lineages. The neutralizing antibody titers against the prototype D614G and the epidemic variant XBB.1.16 were 19666 and 13274, respectively. RBDco induced mice secrete interferon-γ (IFN-γ) under the stimulation of RBD proteins of SARS-CoV-2 variants. In the mouse challenge model, RBDco treatment led to a 10-fold reduction in the viral load in the lungs of mice after the challenge. These results suggest that RBDco can induce a bnAb response and cellular immune response in animals, thereby preventing the occurrence of COVID-19. Furthermore, the sequential immunization results showed an improved neutralizing antibody titer in RBDco-boosted groups relative to the inactivated group. Enhanced differentiation of memory T cells was observed in the RBDco-boosted group. Overall, RBDco can induce bnAbs in animals via chimeric RBDs with the SARS-CoV-2 VOC in different lineages and is a candidate for mRNA vaccine for a rapid response to viral mutations.
Keywords: SARS-CoV-2, broadly neutralizing antibody, Variant of Concern, Receptor-binding domain, Fc fragment
Received: 11 Dec 2024; Accepted: 10 Mar 2025.
Copyright: © 2025 Yang, Tang, Sun, Xi, Peng, Yan, Teng, Zang and Jiang. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence:
Yang Zang, Changchun BCHT Biotechnology Co.,Ltd., Changchun, China
Chunlai Jiang, National Engineering Laboratory of AIDS Vaccine, School of life science, Jilin University, Changchun, 130012, Jilin Province, China
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