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过氧化物酶体增殖物激活受体激动剂作为新冠疫苗的有效佐剂:通过修饰免疫遗传学——文献综述

PPAR agonists as effective adjuvants for COVID-19 vaccines, by modifying immunogenetics: a review of literature.

作者信息

AbdelMassih Antoine Fakhry, Menshawey Rahma, Ismail Jumana H, Husseiny Reem J, Husseiny Yousef M, Yacoub Shenoda, Kamel Aya, Hozaien Rafeef, Yacoub Elaria, Menshawey Esraa, Abdelmalek Abanoub, Abouelazaem Ahmed, Elhatw Ahmed, Aboelmaaty Ahmed, Shahib Alaaelrahman, Mansour Amany, Kamal Aya, Mohamed Basant, Atif Bemen, Ghabreal Beshoy, Abdelmalak Catherine, Ibrahim David, Elsaify Ebtesam, Magdy Farah, Hanna Farid G, Hafez Hadeer, Dahir Hafsa, Merhom Kerlos, Ahmed Maram, Bishara Mariam, Tawfik Mina, Youssef Mina, El Sharnouby Mohamed, Hamouda Mourad, Ammar Musheera, Ali Nada, Daniel Nada, El-Husseiny Nadine, Abdelraouf Noha, Abdelhameed Nuran K, Ahmed Radwa, Othman Radwa, Mohamadein Rahma, Allam Rana, Elgendy Rana, Shebl Rana, Elsherbiney Saged, Fouad Sarah, Emel Sara, Owais Sara, Hetta Sarah, El-Saman Samah, Abdelalim Shaimaa, Galal Sherin, Asar Yara, Osman Yara, Khalaf Yasmeen, Aziz Youstina, Khafagy Yousra, Gamal Nervana, Castaldi Biagio

机构信息

Pediatric Cardiology Unit, Pediatrics' Department, Cairo University Children Hospital, Faculty of Medicine, Cairo University, Kasr Al Ainy Street, Cairo, 12411, Egypt.

Pediatric Cardio-Oncology Department, Children Cancer Hospital of Egypt (57357), Cairo, Egypt.

出版信息

J Genet Eng Biotechnol. 2021 May 31;19(1):82. doi: 10.1186/s43141-021-00179-2.

Abstract

BACKGROUND

Several coronavirus vaccine have been fast-tracked to halt the pandemic, the usage of immune adjuvants that can boost immunological memory has come up to the surface. This is particularly of importance in view of the rates of failure of seroconversion and re-infection after COVID-19 infection, which could make the vaccine role and response debatable. Peroxisome proliferator-activated receptors (PPARs) have an established immune-modulatory role, but their effects as adjuvants to vaccination have not been explored to date. It is increasingly recognized that PPAR agonists can upregulate the levels of anti-apoptotic factors such as MCL-1. Such effect can improve the results of vaccination by enhancing the longevity of long-lived plasma cells (LLPCs). The interaction between PPAR agonists and the immune system does not halt here, as T cell memory is also stimulated through enhanced T regulatory cells, antagonizing PD-L1 and switching the metabolism of T cells to fatty acid oxidation, which has a remarkable effect on the persistence of T memory cells. What is even of a more significant value is the effect of PPAR gamma on ensuring a profound secretion of antibodies upon re-exposure to the offending antigen through upregulating lipoxin B4, therefore potentially assisting the vaccine response and deterring re-infection.

SHORT CONCLUSION

In view of the above, we suggest the use of PPAR as adjuvants to vaccines in general especially the emerging COVID-19 vaccine due to their role in enhancing immunologic memory through DNA-dependent mechanisms.

摘要

背景

为遏制大流行,多种冠状病毒疫苗已进入快速审批通道,能够增强免疫记忆的免疫佐剂的应用已浮出水面。鉴于新冠病毒感染后血清转化失败率和再次感染率,这一点尤为重要,因为这可能使疫苗的作用和反应存在争议。过氧化物酶体增殖物激活受体(PPARs)具有既定的免疫调节作用,但迄今为止尚未探索其作为疫苗佐剂的效果。人们越来越认识到,PPAR激动剂可上调抗凋亡因子如MCL-1的水平。这种作用可通过延长长寿浆细胞(LLPCs)的寿命来改善疫苗接种效果。PPAR激动剂与免疫系统之间的相互作用不止于此,因为T细胞记忆也通过增强调节性T细胞、拮抗PD-L1以及将T细胞代谢转换为脂肪酸氧化而受到刺激,这对T记忆细胞的持久性有显著影响。更具重要价值的是,PPARγ通过上调脂氧素B4,在再次接触致病抗原时确保抗体大量分泌,从而可能辅助疫苗反应并防止再次感染。

简短结论

鉴于上述情况,我们建议一般将PPAR用作疫苗佐剂,尤其是对于新兴的新冠疫苗,因为它们通过依赖DNA的机制在增强免疫记忆方面发挥作用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f939/8167002/768199a4ecf6/43141_2021_179_Fig1_HTML.jpg

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