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《Nature，3月25日，Bispecific IgG neutralizes SARS-CoV-2 variants and prevents escape in mice》

  • 来源专题：COVID-19科研动态监测
  • 编译者： zhangmin
  • 发布时间：2021-03-29

  • Bispecific IgG neutralizes SARS-CoV-2 variants and prevents escape in mice
    Raoul De Gasparo, Mattia Pedotti, […]Luca Varani
    Nature (2021)

    Abstract
    Neutralizing antibodies targeting the receptor binding domain (RBD) of the SARS-CoV-2 Spike (S) are among the most promising approaches against coronavirus disease 2019 (COVID-19)1,2. We developed a bispecific, IgG1-like molecule (CoV-X2) based on two antibodies derived from COVID-19 convalescent donors, C121 and C1353. CoV-X2 simultaneously binds two independent sites on the RBD and, unlike its parental antibodies, prevents detectable S binding to Angiotensin-Converting Enzyme 2 (ACE2), the virus cellular receptor. Furthermore, CoV-X2 neutralizes SARS-CoV-2 and its variants of concern, as well as the escape mutants generated by the parental monoclonals. In a novel animal model of SARS-CoV-2 infection with lung inflammation, CoV-X2 protects mice from disease and suppresses viral escape. Thus, simultaneous targeting of non-overlapping RBD epitopes by IgG-like bispecific antibodies is feasible and effective, combining into a single molecule the advantages of antibody cocktails.

  • 原文来源：https://www.nature.com/articles/s41586-021-03461-y
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    • 来源专题：COVID-19科研动态监测
    • 编译者：zhangmin
    • 发布时间：2021-03-22
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  • 《Nature，3月3日，Immunogenicity of prime-boost protein subunit vaccine strategies against SARS-CoV-2 in mice and macaques》
    • 来源专题：COVID-19科研动态监测
    • 编译者：zhangmin
    • 发布时间：2021-03-09
    • Immunogenicity of prime-boost protein subunit vaccine strategies against SARS-CoV-2 in mice and macaques Hyon-Xhi Tan, Jennifer A. Juno, Wen Shi Lee, Isaac Barber-Axthelm, Hannah G. Kelly, Kathleen M. Wragg, Robyn Esterbauer, Thakshila Amarasena, Francesca L. Mordant, Kanta Subbarao, Stephen J. Kent & Adam K. Wheatley Nature Communications volume 12, Article number: 1403 (2021) Abstract SARS-CoV-2 vaccines are advancing into human clinical trials, with emphasis on eliciting high titres of neutralising antibodies against the viral spike (S). However, the merits of broadly targeting S versus focusing antibody onto the smaller receptor binding domain (RBD) are unclear. Here we assess prototypic S and RBD subunit vaccines in homologous or heterologous prime-boost regimens in mice and non-human primates. We find S is highly immunogenic in mice, while the comparatively poor immunogenicity of RBD is associated with limiting germinal centre and T follicular helper cell activity. Boosting S-primed mice with either S or RBD significantly augments neutralising titres, with RBD-focussing driving moderate improvement in serum neutralisation. In contrast, both S and RBD vaccines are comparably immunogenic in macaques, eliciting serological neutralising activity that generally exceed levels in convalescent humans. These studies confirm recombinant S proteins as promising vaccine candidates and highlight multiple pathways to achieving potent serological neutralisation.
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