Antigen multimerization on a nanoparticle can result in improved neutralizing antibody responses. A platform that has been successfully used for displaying antigens from a number of different viruses is ferritin, a self-assembling protein nanoparticle that allows the attachment of multiple copies (24 monomers or 8 trimers) of a single antigen. Here, we design two-component ferritin variants that allow the attachment of two different antigens on a single particle in a defined ratio and geometric pattern. The two-component ferritin was specifically designed for trimeric antigens, accepting four trimers per particle for each antigen, and was tested with antigens derived from HIV-1 envelope (Env) and influenza hemagglutinin (HA). Particle formation and the presence of native-like antigen conformation were confirmed through negative-stain electron microscopy and antibody-antigen binding analysis. Immunizations in guinea pigs with two-component ferritin particles, displaying diverse Env, HA, or both antigens, elicited neutralizing antibody responses against the respective viruses. The results provide proof-of-principle for the self-assembly of a two-component nanoparticle as a general technology for multimeric presentation of trimeric antigens.

Ivelin S. Georgiev

Michael Gordon Joyce

Rita E. Chen

Kwanyee Leung

Krisha McKee

Aliaksandr Druz

Joseph G. Van Galen

Masaru Kanekiyo

Yaroslav Tsybovsky

Eun Sung Yang

Yongping Yang

Priyamvada Acharya

Marie Pancera

Paul V. Thomas

Timothy Wanninger

Hadi M. Yassine

Ulrich Baxa

Nicole A. Doria-Rose

Cheng Cheng

Barney S. Graham

John R. Mascola

Peter D. Kwong

ACS Infectious Diseases

ACS INFECTIOUS DISEASES 将成为第一本强调化学及其在这一多学科和合作研究领域中的作用的期刊。该杂志将涵盖各种主题，包括但不限于：*发现和开发新的抗菌药物——通过基于靶点或表型的方法以及与抗菌药物产生协同作用的化合物进行鉴定。*药物的表征和验证靶点或通路——使用单一靶点和全基因组敲除和敲除、生化研究、结构生物学、促进潜在药物靶点的表征和优先排序的新技术。* 耐药性机制——促进我们对耐药性理解的基础研究；预防耐药性的策略。* 作用机制——使用遗传、代谢组学和基于活性和亲和力的蛋白质分析来阐明临床和实验性抗菌剂的作用机制。* 宿主-病原体相互作用——研究宿主-病原体的工具相互作用，宿主和病原体的细胞生物化学，以及病原体与宿主微生物群的分子相互作用。*传染病的小分子疫苗佐剂。*病毒和细菌生物化学和分子生物学。

ACS Infectious Diseases is a journal that emphasizes the role of chemistry in this multidisciplinary and collaborative research field. The journal covers a variety of topics, including but not limited to: * Discovery and development of new antibacterial agents—identifying compounds that act synergistically with antibacterial drugs through target-based or phenotypic approaches. * Characterization of drugs and validation of targets or pathways—using single-target and whole-genome knockout and knockdown, biochemical studies, structural biology, and new technologies to facilitate the characterization and prioritization of potential drug targets. * Mechanisms of resistance—basic research that enhances our understanding of resistance; strategies for preventing resistance. * Mechanisms of action—elucidating the mechanisms of clinical and experimental antibacterial agents using genetics, metabolomics, and activity- and affinity-based protein analyses. * Host-pathogen interactions—studying the interactions between host and pathogen, the cell biochemistry of hosts and pathogens, and the molecular interactions between pathogens and host microbiomes. * Small molecule vaccine adjuvants for infectious diseases. * Biochemistry and molecular biology of viruses and bacteria.

《ACS Infectious Diseases》是一本专注于化学及其在多学科合作研究领域中作用的期刊。该杂志涵盖多个主题，包括但不限于：* 新抗菌药物的发现与开发——通过靶点或表型的方法，识别与抗菌药物协同作用的化合物。* 药物的表征与靶点或通路的验证——采用单一靶点和全基因组敲除、敲除、生化研究、结构生物学等新技术，促进潜在药物靶点的表征与优先排序。* 耐药机制——基础研究促进我们对耐药性的理解；预防耐药性的策略。* 作用机制——利用遗传学、代谢组学及基于活性和亲和力的蛋白质分析，阐明临床和实验性抗菌剂的作用机制。* 宿主-病原体相互作用——研究宿主与病原体之间的相互作用、宿主和病原体的细胞生物化学，以及病原体与宿主微生物群的分子相互作用。* 传染病的小分子疫苗佐剂。* 病毒和细菌的生物化学与分子生物学。

ACS Infect. Dis.

Two-Component Ferritin Nanoparticles for Multimerization of Diverse Trimeric Antigens

Two-component ferritin variants that allow the attachment of two different antigens on a single particle in a defined ratio and geometric pattern are designed, providing proof-of-principle for the self-assembly of a two-component nanoparticle as a general technology for multimeric presentation of trimeric antigen.

两组分铁蛋白纳米颗粒用于多种三聚体抗原的多聚化

Category	Quartile
医学	2
医学, 药物化学	2
医学, 传染病学	2

Two-Component Ferritin Nanoparticles for Multimerization of Diverse Trimeric Antigens

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