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SARS-CoV-2 德尔塔（B.1.617.2）刺突蛋白与 Alum-3M-052 佐剂增强抗体产生和中和能力。

SARS-CoV-2 delta (B.1.617.2) spike protein adjuvanted with Alum-3M-052 enhances antibody production and neutralization ability.

机构信息

Guangzhou Women and Children's Medical Center, Guangzhou Medical University, Guangzhou, China.

NHC Key Laboratory of Male Reproduction and Genetics, Guangdong Provincial Reproductive Science Institute (Guangdong Provincial Fertility Hospital), Guangzhou, China.

出版信息

Front Public Health. 2023 Jan 6;10:976686. doi: 10.3389/fpubh.2022.976686. eCollection 2022.

DOI:10.3389/fpubh.2022.976686
PMID:36684881
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC9853420/
Abstract

BACKGROUND: Optimizing adjuvant is one of the critical methods to improve the vaccine. 3M-052, a novel TLR7/8 agonist which was designed for slow dissemination at the injection site, has a potential as adjuvant, but its performance as a vaccine adjuvant for SARS-CoV-2 (B.1.617.2) spike protein has not been studied. The present study aimed to evaluate the effect of Alum-3M-052 as an adjuvant to improve mice serum antibody titers and pseudovirus neutralization efficiency. METHOD: Female Balb/c mice were immunized 3 times at day 0, 7 and 21 intramuscularly with SARS-CoV-2 (B.1.617.2) spike protein and adjuvant (Alum or Alum-3M-052). Mice serum was collected weekly since day 7. Antibody titers of mice serum anti-SARS-CoV-2 (B.1.617.2) IgG and IgM were detected by ELISA. Inhibition rates of mice serum blocking SARS-CoV-2 (B.1.617.2) spike protein binding to ACE2 were detected by SARS-CoV-2 (B.1.617.2) Inhibitor Screening Kit. Neutralization efficiencies of mice serum against both SARS-CoV-2 (BA.2.12.1) pseudovirus and SARS-CoV-2 (B.1.617.2) pseudovirus were detected by pseudovirus neutralizing assay. RESULT: Serum of mice immunized by SARS-CoV-2 (B.1.617.2) spike protein adjuvanted with Alum-3M-052 had highest antibody titers and higher neutralization efficiency against both SARS-CoV-2 (BA.2.12.1) pseudovirus and SARS-CoV-2 (B.1.617.2) pseudovirus. Besides, neutralization efficiency of anti-SARS-CoV-2 (B.1.617.2) spike protein antibody against SARS-CoV-2 (BA.2.12.1) pseudovirus was lower than that of SARS-CoV-2 (B.1.617.2) pseudovirus. CONCLUSION: Alum-3M-052 rapidly increased the titer of anti-SARS-CoV-2 (B.1.617.2) spike protein neutralizing antibodies and enhanced the neutralization ability against pseudoviruses and variants. This study provided evidence for the application of Alum-3M-052 as an adjuvant in COVID-19 vaccines production.

摘要

背景：优化佐剂是提高疫苗效果的关键方法之一。3M-052 是一种新型 TLR7/8 激动剂，设计用于在注射部位缓慢释放，具有作为佐剂的潜力，但尚未研究其作为 SARS-CoV-2（B.1.617.2）刺突蛋白疫苗佐剂的性能。本研究旨在评估 Alum-3M-052 作为佐剂提高小鼠血清抗体滴度和假病毒中和效率的效果。

方法：雌性 Balb/c 小鼠在 0、7 和 21 天经肌肉注射 SARS-CoV-2（B.1.617.2）刺突蛋白和佐剂（Alum 或 Alum-3M-052）进行 3 次免疫。从第 7 天开始每周采集小鼠血清。通过 ELISA 检测小鼠血清抗 SARS-CoV-2（B.1.617.2）IgG 和 IgM 抗体滴度。通过 SARS-CoV-2（B.1.617.2）抑制剂筛选试剂盒检测小鼠血清阻断 SARS-CoV-2（B.1.617.2）刺突蛋白与 ACE2 结合的抑制率。通过假病毒中和试验检测小鼠血清对 SARS-CoV-2（BA.2.12.1）假病毒和 SARS-CoV-2（B.1.617.2）假病毒的中和效率。

结果：用 Alum-3M-052 佐剂免疫的 SARS-CoV-2（B.1.617.2）刺突蛋白疫苗的小鼠血清具有最高的抗体滴度和对 SARS-CoV-2（BA.2.12.1）假病毒和 SARS-CoV-2（B.1.617.2）假病毒的更高中和效率。此外，抗 SARS-CoV-2（B.1.617.2）刺突蛋白抗体对 SARS-CoV-2（BA.2.12.1）假病毒的中和效率低于对 SARS-CoV-2（B.1.617.2）假病毒的中和效率。

结论：Alum-3M-052 可快速提高抗 SARS-CoV-2（B.1.617.2）刺突蛋白中和抗体的滴度，并增强对假病毒和变体的中和能力。本研究为 Alum-3M-052 作为 COVID-19 疫苗佐剂的应用提供了证据。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8715/9853420/e6f130e79c90/fpubh-10-976686-g0004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8715/9853420/d223fa748115/fpubh-10-976686-g0001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8715/9853420/2432e079bffa/fpubh-10-976686-g0002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8715/9853420/9bb8229b9eb6/fpubh-10-976686-g0003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8715/9853420/e6f130e79c90/fpubh-10-976686-g0004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8715/9853420/d223fa748115/fpubh-10-976686-g0001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8715/9853420/2432e079bffa/fpubh-10-976686-g0002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8715/9853420/9bb8229b9eb6/fpubh-10-976686-g0003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8715/9853420/e6f130e79c90/fpubh-10-976686-g0004.jpg

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引用本文的文献

[1]
The development and application of pseudoviruses: assessment of SARS-CoV-2 pseudoviruses.

PeerJ. 2023

本文引用的文献

[1]
BA.2.12.1, BA.4 and BA.5 escape antibodies elicited by Omicron infection.

Nature. 2022-8

[2]
A bivalent vaccine containing D614G and BA.1 spike trimer proteins or a BA.1 spike trimer protein booster shows broad neutralizing immunity.

J Med Virol. 2022-9

[3]
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Nature. 2021-8

[8]
SARS-CoV-2 RBD trimer protein adjuvanted with Alum-3M-052 protects from SARS-CoV-2 infection and immune pathology in the lung.

Nat Commun. 2021-6-11

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Nat Biotechnol. 2020-7-23

[10]
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Sci Immunol. 2020-6-19

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