中国科学院生物物理研究所,表观遗传调控与干预重点实验室,研究组长
1989 - 1994 北京医科大学(现北京大学医学部),临床医学,本科
1994 - 1997 北京协和医院,住院医师
1997 - 2001 北京协和医科大学,博士研究生
2001 - 2003 范德比尔特大学,博士后
2003 - 2009 加州大学旧金山分校,博士后
2009 - 2011 加州大学旧金山分校,助理研究员
2011 - 至今 中国科学院生物物理所,研究员
B淋巴细胞负责产生抗体,在感染免疫、疫苗免疫和肿瘤免疫中都发挥重要作用。我们实验室致力于利用和发展一系列前沿技术,对B细胞免疫反应的机理进行研究;并积极推动将基础研究的新发现转化到创新疫苗设计等应用领域。实验室的主要研究内容包括:
1. B细胞免疫应答的天然免疫信号调控
B细胞不仅能用抗原受体识别病毒抗原,还能用天然免疫受体TLR识别来判断抗原属性。我们发现这两种信号的协同能够将B细胞转变成专职抗原提呈细胞来启动CD4+ T细胞反应(Immunity2018)。这个发现突破了只有树突状细胞才能启动T细胞应答的传统认知,对阐明抗病毒免疫、自身免疫发病的机理,以及临床应用转化都有重要意义。
2. 广谱中和抗体的形成机制
广谱中和抗体(bnAb)能够有效应对病毒免疫逃逸。但是,由于形成机制不明,严重制约了相关疫苗的发展。在研究Qb病毒样颗粒抗原免疫应答特征过程中,我们发现生发中心竞争可以在不影响亲和力成熟的基础上促进低亲和力B细胞参与反应、扩大克隆多样性和防变异抗体演化(in revision),为阐明bnAb的产生机制和发展高变异病毒疫苗提供了重要线索。
3. 长效体液免疫记忆形成的表观遗传机理
B细胞记忆是体液免疫记忆的基础。临床观察发现不同疫苗诱导长效免疫记忆的能力存在明显差别。例如,接种天花疫苗(牛痘)可以产生终身免疫保护,而某些灭活病毒疫苗产生的保护时效有限。记忆B细胞的分化受到表观遗传修饰和转录因子的调控。通过对抗病毒记忆B细胞的表观遗传特征的分析,我们发现这些记忆B细胞在形成过程中获得了天然免疫记忆能力(Science Advances2024) 。这个发现为揭示长效体液免疫记忆的细胞和分子本质、以及表观遗传调控机理奠定了基础。
4. 新概念纳米疫苗
传统疫苗技术难以应对新发、突发传染病(如COVID-19)和各种重大传染病(HIV、流感、慢性病毒肝炎等)对公共卫生构成的挑战。结合原创免疫理论发现,我们实验室采用了合成生物学设计理念发展了病原样抗原(Pathogen-like antigen, PLA) 的新概念疫苗策略,并成功应用于新型SARS-CoV-2疫苗的临床前研究(Cell Reports Medicine2021)。与其他疫苗平台技术的对比,PLA疫苗显现出更优异的免疫原性与免疫记忆形成能力(in revision)。基于这些研究发现,我们正在将PLA技术更广泛应用于HIV、流感病毒、HBV等高难度疫苗的研发。
1.Zhu X, Hong S, Bu J, Liu Y, Liu C, Li R, Zhang T, Zhang Z, Li L, Zhou X, Hua Z*, Zhu B*,Hou B*. Antiviral memory B cells exhibit enhanced innate immune response facilitated by epigenetic memory.Sci Adv. 2024 Mar 29;10(13):eadk0858. doi: 10.1126/sciadv.adk0858. Epub 2024 Mar 29. PMID: 38552009; PMCID: PMC10980274.
2.Cao S, Zhang Q, Song L, Xiao M, Chen Y, Wang D, Li M, Hu J, Lin L, Zheng Y, Zhou K, Ye S, Zhou J, Zhou YN, Cui J, Wang J, Sun J, Tao J, Chen Z, Chen R, Zhou P, Shi Z, Wei S, Zhao L, Wang H*, Tong X*, Li X*, Men D*,Hou B*, Zhang XE*. Dysregulation of Innate and Adaptive Immune Responses in Asymptomatic SARS-CoV-2 Infection with Delayed Viral Clearance.Int J Biol Sci. 2022 Jul 11;18(12):4648-4657. doi: 10.7150/ijbs.72963. PMID: 35874943; PMCID: PMC9305270.
3. Guo C, Peng Y, Lin L, Pan X, Fang M, Zhao Y, Bao K, Li R, Han J, Chen J, Song TZ, Feng XL, Zhou Y, Zhao G, Zhang L, Zheng Y, Zhu P, Hang H, Zhang L, Hua Z*, Deng H*,Hou B*. A pathogen-like antigen-based vaccine confers immune protection against SARS-CoV-2 in non-human primates.Cell Rep Med. 2021 Nov 16;2(11):100448. doi: 10.1016/j.xcrm.2021.100448. Epub 2021 Oct 23. PMID: 34723223; PMCID: PMC8536523.
4. Lin X, Twelkmeyer T, Zhu D, Zhang L, Zhao Y, Zhang C, Iwakura Y, Meng G, Hua Z, Yan B, Liu WJ, Luo Z, Gong S, Chen H, Li S*,Hou B*, Tang H*. Homeostatic regulation of T follicular helper and antibody response to particle antigens by IL-1Ra of medullary sinus macrophage origin.Proc Natl Acad Sci U S A. 2021 Apr 27;118(17):e2019798118. doi: 10.1073/pnas.2019798118. PMID: 33875594; PMCID: PMC8092388.
5. Hua Z*,Hou B*. The role of B cell antigen presentation in the initiation of CD4+T cell response.Immunol Rev. 2020 Apr 18. doi: 10.1111/imr.12859. [Epub ahead of print] Review. PMID:32304104
6. Hong S, Zhang Zhimin, Liu H, Tian M, Zhu X, Zhang Zhuqiang, Wang W, Zhu B, Zhou X, Zhang F, Ge Q, Tang H*, Hua Z*,Hou B*.B cells are the dominant antigen-presenting cells that activate naive CD4+T cells upon immunization with a virus-derived nanoparticle antigen.Immunity, 2018, Sep 21. pii: S1074-7613(18)30353-4. doi: 10.1016/j.immuni.2018.08.012. [Epub ahead of print]
◆Selected and recommended by Faculty of 1000.
7. Tian M, Hua Z, Hong S, Zhang Z, Liu C, Lin L, Chen J, Zhang W, Zhou X, Zhang F, DeFranco AL andHou B*. B Cell-Intrinsic MyD88 Signaling Promotes Initial Cell Proliferation and Differentiation To Enhance the Germinal Center Response to a Virus-like Particle.J Immunol.2018 February 1. 200 (3) 937-948. PMID: 29282308
8. Liao W, Hua Z, Liu C, Lin L, Chen R,Hou B*.Characterization of T-Dependent and T-Independent B Cell Responses to a Virus-like Particle.J Immunol.2017 May 15. PMID:28416599
9. Hua Z, Gross AJ, Lamagna C, Ramos-Hernández N, Scapini P, Ji M, Shao H, Lowell CA,Hou B*,DeFranco AL*. Requirement for MyD88 signaling in B cells and dendritic cells for germinal center anti-nuclear antibody production in Lyn-deficient mice.J Immunol.2014 Feb 1;192(3):875-85. PMID: 24379120
10. Hua Z,Hou B*.TLR signaling in B cell development and activation.Cell. Mol. Immunol.,Vol.10, 103-106, 2013. PMID: 23241902
11. DeFranco AL, Rookhuizen D,Hou B.Contribution of TLR signaling to germinal center antibody responses.Immunological reviews.2012 May;247(1):64-72. PMID: 22500832.
12. Kirkland D, Benson A, Mirpuri J, Pifer R,Hou B,Defranco AL, Yarovinsky F. B Cell-Intrinsic MyD88 Signaling Prevents the Lethal Dissemination of Commensal Bacteria during Colonic Damage.Immunity.2012 Feb 24;36(2):228-38. PMID: 22306056.
13.Hou B*,Saudan P, Ott G, Wheeler ML, Ji M, Kuzmich L, Lee L, Coffman R, Bachmann M, DeFranco AL*. Selective utilization of TLR/MyD88 signaling in B cells for enhancement of the anti-viral germinal center response.Immunity2011 Mar 25;34(3):375-84. PMID: 21353603.
◆Selected and recommended by Faculty of 1000.
14.Hou B*,Benson A, Kuzmich L, DeFranco AL, Yarovinsky F*. Critical coordination of innate immune defense to Toxoplasma gondii by dendritic cells responding via their Toll-like receptors.Proc Natl Acad Sci USA.2011 Jan 4;108(1):278-83. PMID: 21173242.
15.Hou B, Reizis B, DeFranco AL. Toll-like receptor-mediated dendritic cell-dependent and –independent stimulation of innate and adaptive immunity.Immunity2008 Aug; 29(2): 272-82. PMID: 18656388.
◆Highlighted in News View. Immunity 2008
◆Selected and evaluated for the Faculty of 1000
1. 活化CD4+ T细胞的方法,发明人:侯百东;洪胜;华兆琳;唐宏;专利号:ZL 2019 8 0052317.0
2. 病原样抗原疫苗及其制备方法,发明人:侯百东;华兆琳;郭畅;专利号:ZL 2020 1 1480939.4
3. 针对新型冠状病毒感染的疫苗组合物,发明人:侯百东;专利号:ZL 2020 1 1480978.4
(资料来源:侯百东研究员,2024-09-13)