RBD design increases the functional antibody titers elicited by SARS-CoV-2 spike vaccination

IF 4.5 2区医学 Q1 PHARMACOLOGY & PHARMACY

Antiviral research Pub Date : 2024-06-18 DOI:10.1016/j.antiviral.2024.105937

Thayne H. Dickey , Nichole D. Salinas , Palak Patel , Sachy Orr-Gonzalez , Tarik Ouahes , Holly McAleese , Brandi L. Richardson , Myesha Singleton , Michael Murphy , Brett Eaton , Jennifer L. Kwan , Michael R. Holbrook , Lynn E. Lambert , Niraj H. Tolia

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引用次数: 0

Abstract

Most COVID-19 vaccines contain the SARS-CoV-2 spike protein as an antigen, but they lose efficacy as neutralizing antibody titers wane and escape variants emerge. Modifying the spike antigen to increase neutralizing antibody titers would help counteract this decrease in titer. We previously used a structure-based computational design method to identify nine amino acid changes in the receptor-binding domain (RBD) of spike that stabilize the RBD and increase the neutralizing antibody titers elicited by vaccination. Here, we introduce those enhancing amino acid changes into a full-length spike (FL-S-2P) ectodomain representative of most approved vaccine antigens. These amino acid changes can be incorporated into the FL-S-2P protein without negatively effecting expression or stability. Furthermore, the amino acid changes improved functional antibody titers in both mice and monkeys following vaccination. These amino acid changes could increase the duration of protection conferred by most COVID-19 vaccines.

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RBD 设计可提高 SARS-CoV-2 穗状疫苗激发的功能性抗体滴度。

大多数 COVID-19 疫苗都含有作为抗原的 SARS-CoV-2 穗状病毒蛋白，但随着中和抗体滴度的降低和逃逸变种的出现，这些疫苗的效力也随之降低。改造尖峰抗原以提高中和抗体滴度将有助于抵消滴度的下降。我们之前使用了一种基于结构的计算设计方法，确定了尖峰抗原受体结合域（RBD）中的九个氨基酸变化，这些变化可以稳定 RBD 并提高疫苗接种所激发的中和抗体滴度。在此，我们将这些增强性氨基酸变化引入到代表大多数获批疫苗抗原的全长斯派克（FL-S-2P）外结构域中。这些氨基酸变化可以整合到 FL-S-2P 蛋白中，而不会对其表达或稳定性产生负面影响。此外，氨基酸变化还能提高小鼠和猴子接种疫苗后的功能性抗体滴度。这些氨基酸变化可以延长大多数 COVID-19 疫苗的保护期。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Antiviral research 医学-病毒学

CiteScore

17.10

自引率

3.90%

发文量

157

审稿时长

34 days

期刊介绍： Antiviral Research is a journal that focuses on various aspects of controlling viral infections in both humans and animals. It is a platform for publishing research reports, short communications, review articles, and commentaries. The journal covers a wide range of topics including antiviral drugs, antibodies, and host-response modifiers. These topics encompass their synthesis, in vitro and in vivo testing, as well as mechanisms of action. Additionally, the journal also publishes studies on the development of new or improved vaccines against viral infections in humans. It delves into assessing the safety of drugs and vaccines, tracking the evolution of drug or vaccine-resistant viruses, and developing effective countermeasures. Another area of interest includes the identification and validation of new drug targets. The journal further explores laboratory animal models of viral diseases, investigates the pathogenesis of viral diseases, and examines the mechanisms by which viruses avoid host immune responses.