约翰斯·霍普金斯大学科学家研发出结核病鼻喷DNA疫苗

研究结果发表在《临床研究杂志》（*Journal of Clinical Investigation*）上。 结核病折磨人类至少已有6000年历史，至今仍是世界上最致命的传染病之一。据世界卫生组织（WHO）统计，全球约四分之一的人口（约20亿人）携带无症状的潜伏性结核感染。2024年，有超过1000万人患上活动性结核病，120万人死于该疾病，使其成为单一传染性病原体导致死亡的首要原因。 **结核病治疗需要新方法** WHO强调需要能够辅助现有药物治疗的治疗性疫苗。此类疫苗有望缩短漫长的治疗方案并改善治疗结果，特别是考虑到多药联合疗法难以被患者坚持完成，且耐药型结核病仍在继续传播。 约翰斯·霍普金斯大学这项新研究的结果表明，这种疫苗方法有助于应对这些挑战。 研究主要作者、约翰斯·霍普金斯结核病研究中心成员及约翰斯·霍普金斯大学医学院医学助理教授、医学博士Styliani Karanika表示：“我们的鼻内DNA融合疫苗与一线结核病药物治疗联合使用，帮助受感染小鼠更快清除致病菌，减轻了肺部炎症，并防止了治疗结束后的复发。该疫苗还增强了贝达喹啉（bedaquiline）、普托马尼和利奈唑胺这一强效结核病药物组合的疗效，这表明它可以与耐药结核病的治疗方法联用，帮助机体对抗疾病，甚至是难治病例。” **实验性结核病疫苗的作用机制** 据Karanika介绍，该疫苗结合了relMtb和Mip3α两种基因，并通过鼻腔给药，以利用多种可能增强结核免疫力的生物机制。 她说：“首先，结核杆菌拥有一个名为relMtb的基因，该基因产生RelMtb蛋白，帮助微生物通过进入药物耐受持留状态，在抗生素暴露、低氧和营养受限等恶劣条件下生存。将relMtb与Mip3α基因融合后会产生一种信号，吸引未成熟树突状细胞——这是一种关键细胞，能摄取结核蛋白并将其‘呈递’给T细胞，而T细胞是协助协调针对结核杆菌发起针对性攻击的免疫细胞。” 该疫苗的设计还旨在将免疫活动集中在结核感染起始部位。 Karanika说：“最后，鼻内给药将疫苗接种集中在结核感染发生的肺部呼吸道黏膜，有助于在气道和肺部产生持久的局部T细胞免疫，同时引发全身免疫反应。” **动物研究中的强效免疫反应** * *Draft:* 通过结合这些机制，研究人员旨在直接加强呼吸道内的免疫防御。 * *Sentence 2:* "In mouse experiments, the vaccine increased recruitment and activation of dendritic cells, improved the organization of dendritic cells and T cells within lung tissue, and generated durable, antigen-stimulated T-cell responses -- both locally and systemically -- from CD4 (also known as helper T cells) and CD8 (also known as killer T-cells)." * *Key terms:* mouse experiments (小鼠实验), recruitment and activation (募集与活化), dendritic cells (树突状细胞), improved the organization (改善...的组织/排列), lung tissue (肺组织), durable (持久的), antigen-stimulated (抗原刺激的), T-cell responses (T细胞反应), locally and systemically (局部和全身), CD4/CD8 (CD4/CD8), helper T cells (辅助性T细胞), killer T-cells (杀伤性T细胞/细胞毒性T细胞). * *Structure:* The sentence lists three main effects: 1. increased recruitment/activation, 2. improved organization, 3. generated responses. * *Draft:* 在小鼠实验中，该疫苗增加了树突状细胞的募集和活化，改善了肺组织内树突状细胞和T细胞的组织结构，并在局部和全身产生了来自CD4（也称为辅助性T细胞）和CD8（也称为杀伤性T细胞）的持久抗原刺激T细胞反应。 * *Sentence 3:* "The team also evaluated the vaccine in rhesus macaques." * *Key terms:* rhesus macaques (恒河猴). * *Draft:* 该团队还在恒河猴中评估了该疫苗。 * *Sentence 4:* "The nose-delivered DNA vaccine generated measurable TB-specific immune responses in both the bloodstream and airways." * *Key terms:* nose-delivered (鼻内给药/鼻喷/经鼻), DNA vaccine (DNA疫苗), measurable (可测量的), TB-specific (结核病特异性/结核特异性), bloodstream (血液), airways (气道). * *Draft:* 这种经鼻给药的DNA疫苗在血液和气道中均产生了可测量的结核特异性免疫反应。 * *Sentence 5:* "These responses resembled those associated with reduced bacterial levels in the lungs of vaccinated mice." * *Key terms:* resembled (类似于), associated with (与...相关), reduced bacterial levels (细菌水平降低). * *Draft:* 这些反应与接种疫苗的小鼠肺部细菌水平降低相关的反应相似。 * *Sentence 6:* "Researchers observed that the immune responses lasted for at least six months, suggesting the vaccine may provide durable protection." * *Key terms:* lasted for at least six months (持续至少六个月), durable protection (持久保护). * *Draft:* 研究人员观察到免疫反应持续了至少六个月，表明该疫苗可能提供持久的保护作用。 * *Sentence 7:* "However, Karanika notes that the primate study assessed immune activation only and did not test how the animals responded to an actual TB infection." * *Key terms:* Karanika (name, transliterate as 卡拉尼卡), primate study (灵长类动物研究), assessed immune activation only (仅评估了免疫激活), actual TB infection (实际的结核感染). * *Draft:* 然而，Karanika指出，这项灵长类动物研究仅评估了免疫激活，并未测试动物对实际结核感染的反应。 * *Sentence 8:* "She says additional research will be required before the vaccine can advance to human clinical trials." * *Key terms:* additional research (额外研究/进一步研究), advance to (推进至), human clinical trials (人体临床试验). * *Draft:* 她表示，在该疫苗推进到人体临床试验之前，还需要进行更多的研究。 * *Sentence 9:* "“These nonhuman primate data are encouraging because they show that the Mip3α/relMtb vaccine can generate durable, antigen-stimulated immune responses in an animal model whose immune system more closely resembles that of humans,” says Karanika." * *Key terms:* nonhuman primate data (非人类灵长类动物数据), encouraging (令人鼓舞的), Mip3α/relMtb vaccine (Mip3α/relMtb疫苗), animal model (动物模型), immune system (免疫系统), resembles (相似). * *Draft:* Karanika说：“这些非人类灵长类动物数据令人鼓舞，因为它们表明Mip3α/relMtb疫苗可以在免疫系统与人类更相似的动物模型中产生持久的抗原刺激免疫反应。” * *Sentence 10:* "“That gives us an important translational bridge between the mouse efficacy studies and the additional preclinical work needed before human trials.”" * *Key terms:* translational bridge (转化桥梁), mouse efficacy studies (小鼠功效研究/有效性研究), preclinical work (临床前工作). * *Draft:* “这为我们在小鼠有效性研究与人体试验前所需的额外临床前工作之间搭建了一座重要的转化桥梁。” * *Sentence 11:* "Targeting TB Persisters With Immunotherapy" * *Key terms:* Targeting (靶向), TB Persisters (结核持留菌/结核分枝杆菌持留菌), Immunotherapy (免疫疗法). * *Draft:* 利用免疫疗法靶向结核持留菌 * *Sentence 12:* "The researchers believe their results support a broader treatment strategy that focuses on eliminating TB persisters through immunotherapy rather than relying exclusively on antibiotics to kill actively growing bacteria." * *Key terms:* broader treatment strategy (更广泛的治疗策略), eliminating (清除/消除), TB persisters (结核持留菌), relying exclusively on (单纯依赖/仅依赖), antibiotics (抗生素), actively growing bacteria (活跃生长的细菌). * *Draft:* 研究人员认为，他们的结果支持一种更广泛的治疗策略，即侧重于通过免疫疗法清除结核持留菌，而不是单纯依赖抗生素杀灭活跃生长的细菌。 * *Sentence 13:* "Because DNA vaccines are generally stable and can be produced efficiently, the approach could offer practical advantages if future studies demonstrate similar benefits in humans." * *Key terms:* stable (稳定), produced efficiently (高效生产), practical advantages (实际优势). * *Draft:* 由于DNA疫苗通常性质稳定且可高效生产，如果未来的研究证明其在人体中具有类似的益处，该方法可能会提供实际的优势。 * *Sentence 14:* "Along with Karanika, the Johns Hopkins research team included Tianyin Wang, Addis Yilma, Jennie Ruelas Castillo, James Gordy, Hannah Bailey, Darla Quijada, Kaitlyn Fessler, Rokeya Tasneen, Elisa M. Rouse Salcido, Farah Shamma, Harley Harris, Fengyixin Chen, Rowan Bates, Heemee Ton, Jacob Meza, Yangchen Li, Alannah Taylor, Jean Zheng, Jiaqi Zhang, Theodoros Karantanos, Amanda Maxwell, Eric Nuermberger, J. David Peske, Richard Markham and Petros Karakousis." * *Key terms:* Names need to be transliterated or kept as is depending on convention. Usually, in scientific lists, names are often transliterated or kept in English. Given the instruction to be a "professional tech translator", standard practice for lists of authors in Chinese contexts is often to keep the English names to ensure accuracy, or transliterate them. However, for a general audience or press release translation, transliteration is common. Let's look at the names. Many look like Chinese names (Tianyin Wang, Fengyixin Chen, Yangchen Li, Jean Zheng, Jiaqi Zhang). It is best to translate the sentence structure and keep the names in English or provide Chinese characters if obvious (like Wang Tianyin). But without specific instructions to transliterate names, keeping them in English is the safest and most professional approach for scientific accuracy, or transliterating the non-Chinese names while restoring Chinese names. * *Decision:* I will translate the sentence structure and keep the names in English to avoid errors in transliteration, which is standard in many academic translations unless a specific glossary is provided. However, for Chinese names (Tianyin Wang -> 王天音/田音? Fengyixin Chen -> 陈风一心? Yangchen Li -> 李阳晨?), guessing characters is dangerous. I will keep the names in English to ensure 100% accuracy as per the instruction "retain all scientific data and technical details". * *Draft:* 除Karanika外， * *Draft 1 (Mental):* 额外的支持来自吉利德HIV研究学者奖，一个约翰霍普金斯大学结核病研究促进中心发展奖，一个来自约翰霍普金斯大学艾滋病研究中心的HIV/艾滋病中心发展奖，一个Willowcraft基金会奖，一个约翰霍普金斯大学临床科学家奖和Potts纪念基金会。 * *Refining Draft 1:* "Additional support came from..." -> "额外资助来自..." or "额外支持由...提供". "Came from" implies the source. * *Structure:* List the awards clearly. * *Award Names:* * Gilead HIV Research Scholar Award -> 吉利德HIV研究学者奖 * Johns Hopkins University Tuberculosis Research Advancement Center Developmental Award -> 约翰霍普金斯大学结核病研究促进中心发展奖 * Center for HIV/AIDS Developmental Award from the Johns Hopkins University Center for AIDS Research -> 约翰霍普金斯大学艾滋病研究中心颁发的HIV/艾滋病中心发展奖 (or simply 约翰霍普金斯大学艾滋病研究中心HIV/艾滋病中心发展奖) * Willowcraft Foundation Award -> Willowcraft基金会奖 * Johns Hopkins University Clinician Scientist Award -> 约翰霍普金斯大学临床科学家奖 * Potts Memorial Foundation -> Potts纪念基金会 (注明: The text says "and the Potts Memorial Foundation", implying the foundation itself provided support, not necessarily an award *named* "Award" explicitly in the text structure, though often foundations give grants. However, grammatically it's listed as a source of support. I will translate it as "Potts纪念基金会"). * *Draft 2 (Paragraph 1):* 额外资助来自吉利德HIV研究学者奖、约翰霍普金斯大学结核病研究促进中心发展奖、约翰霍普金斯大学艾滋病研究中心颁发的HIV/艾滋病中心发展奖、Willowcraft基金会奖、约翰霍普金斯大学临床科学家奖以及Potts纪念基金会。 * *Draft 2 (Paragraph 2):* Karanika、Gordy、Markham和Karakousis是Mip3α/relMtb疫苗专利PCT/US2023/065584的发明人。作者报告无利益冲突。 4. **Final Polish:** * Check punctuation. Use enumeration commas (、) for lists in Chinese. * Check technical terms. "Developmental Award" -> 发展奖. "Clinician Scientist" -> 临床科学家. "Conflicts of interest" -> 利益冲突. * Formatting: The input has HTML tags `

 

`. I should probably maintain the paragraph structure or just output the text. The prompt asks to translate the content. I will output the text with paragraph breaks corresponding to the input. * *Refined Paragraph 1:* 额外资助来自吉利德HIV研究学者奖（Gilead HIV Research Scholar Award）、约翰霍普金斯大学结核病研究促进中心发展奖（Johns Hopkins University Tuberculosis Research Advancement Center Developmental Award）、约翰霍普金斯大学艾滋病研究中心（Johns Hopkins University Center for AIDS Research）颁发的HIV/艾滋病中心发展奖（Center for HIV/AIDS Developmental Award）、Willowcraft基金会奖（Willowcraft Foundation Award）、约翰霍普金斯大学临床科学家奖（Johns Hopkins University Clinician Scientist Award）以及Potts纪念基金会（Potts Memorial Foundation）。 * *Self-Correction:* The prompt says "Retain all scientific data and technical details". It doesn't explicitly ask to keep English in brackets, but for proper nouns of specific awards, it is sometimes helpful. However, standard professional translation usually translates them directly unless they are very specific codes. I will provide the Chinese translation. If the foundation names are obscure, keeping the English name is safer for identification, or a mix. Let's stick to a clean Chinese translation, keeping names like "Willowcraft" and "Potts" in English or transliterated if standard. Since "Willowcraft" and "Potts" are not universally standardized Chinese names, keeping them in English within the Chinese sentence is often the most professional approach for scientific translation to avoid ambiguity. * *Decision on Names:* Keep "Willowcraft" and "Potts" in English, or transliterate? "Potts" is common (波茨), "Willowcraft" is rare. In high-level scientific translation, retaining the English name for specific entities without standard translations is preferred. * *Revised Paragraph 1:* 额外资助来自吉利德HIV研究学者奖、约翰霍普金斯大学结核病研究促进中心发展奖、约翰霍普金斯大学艾滋病研究中心颁发的HIV/艾滋病中心发展奖、Willowcraft基金会奖、约翰霍普金斯大学临床科学家奖以及Potts纪念基金会。 * *Revised Paragraph 2:* Karanika、Gordy、Markham和Karakousis是Mip3α/relMtb疫苗专利PCT/US2023/065584的发明人。作者报告无利益冲突。 5. **Final Output Generation:** (Combine the paragraphs). 额外资助来自吉利德HIV研究学者奖、约翰霍普金斯大学结核病研究促进中心发展奖、约翰霍普金斯大学艾滋病研究中心颁发的HIV/艾滋病中心发展奖、Willowcraft基金会奖、约翰霍普金斯大学临床科学家奖以及Potts纪念基金会。 Karanika、Gordy、Markham和Karakousis是Mip3α/relMtb疫苗专利PCT/US2023/065584的发明人。作者报告无利益冲突。 *注明 on HTML tags:* The user input contains `

`. I should probably just output the text paragraphs separated by newlines, as the prompt asks for the translation of the *content*. I will output plain text paragraphs. *One final check on "Developmental Award":* Sometimes translated as "发展奖" or "培育奖". "发展奖" is literal and acceptable. "培育奖" is often used for "Career Development Award". Given "Developmental", "发展奖" fits well.