Phase III, Randomized, Single-blind, Placebo-controlled, Multi-center Study to Evaluate Non-interference of Concomitant Administration of Routine Pediatric Vaccines on the Antibody Response of an Investigational Live-attenuated Respiratory Syncytial Virus (RSV) Vaccine in Healthy Infants and Toddlers (CORAL)

This study is a Phase III, randomized, single-blind, placebo-controlled, multi-center study to be conducted in healthy infants and toddlers which will be enrolled at approximately 6 months of age (Cohort 1) and approximately 12 months of age (Cohort 2). The primary objective of the study will be to assess non-inferiority of the RSV infant and toddler (RSVt) vaccine antibody response when administered concomitantly with routine pediatric vaccines at 6 months of age (Diphtheria and Tetanus Toxoids and Acellular Pertussis, Inactivated Poliovirus, Haemophilus b Conjugate and Hepatitis B Vaccine [Vaxelis® or Pentacel® and Recombivax HB®] Prevnar 20®, and RotaTeq®), and 12 months of age (M-M-R II, VARIVAX, and Prevnar 20 or per local country recommendations) compared to when administered non-concomitantly.

开始日期2024-05-13

申办/合作机构

Sanofi Pasteur SA

NCT04490499

/ Completed临床3期

A Hepatitis B Vaccine Challenge Study to Demonstrate the Durability of Protection Against Hepatitis B Virus Infection in Healthy Children Vaccinated Approximately 9 Years Previously With a 2- or 3-Dose Infant Series and Toddler Dose of Vaxelis®

The purpose of this study is to demonstrate the durability of protection against hepatitis B virus (HBV) infection approximately 8-9 years after vaccination with Vaxelis®. This is an estimation study, and no formal hypothesis testing was performed.

开始日期2020-09-02

申办/合作机构

Merck Sharp & Dohme Corp.

NCT03893448

/ Completed临床3期

A Phase 3, Multicenter, Randomized, Double-blind, Active-Comparator-controlled Study to Evaluate the Safety, Tolerability, and Immunogenicity of a 4-dose Regimen of V114 in Healthy Infants (PNEU-PED)

The purpose of this study is to evaluate the safety, tolerability, and immunogenicity of V114 in healthy infants. The primary hypotheses are that: 1) V114 is non-inferior to Prevnar 13™ for the 13 shared serotypes between V114 and Prevnar 13™ based on response rates at 30 days following Dose 3; 2) V114 is non-inferior to Prevnar 13™ for the 2 unique V114 serotypes based on the response rate of the 2 unique V114 serotypes compared with the lowest response rate of any of the shared serotypes in Prevnar 13™, excluding serotype 3, at 30 days following Dose 3; 3) V114 is non-inferior to Prevnar 13™ for the 13 shared serotypes based on anti-pneumococcal polysaccharide (PnPs) serotype-specific immunoglobulin g (IgG) geometric mean concentrations (GMCs) at 30 days following Dose 3; 4) V114 is non-inferior to Prevnar 13™ for the 2 unique V114 serotypes based on the anti-PnPs serotype-specific IgG GMCs of the 2 unique V114 serotypes compared with the lowest IgG GMC of any of the shared serotypes in Prevnar 13™, excluding serotype 3, at 30 days following Dose 3; 5) V114 is non-inferior to Prevnar 13™ for the 13 shared serotypes between V114 and Prevnar 13™ based on anti-PnPs serotype-specific IgG GMCs at 30 days following Dose 4; and 6) V114 is non-inferior to Prevnar 13™ for the 2 unique V114 serotypes based on anti-PnPs serotype-specific IgG GMCs of the 2 unique V114 serotypes compared with the lowest IgG GMC of any of the shared serotypes in Prevnar 13, excluding serotype 3, at 30 days following Dose 4.

开始日期2019-06-19

申办/合作机构

Merck Sharp & Dohme Corp.

100 项与 Hepatitis B vaccine(Merck Sharp & Dohme) 相关的临床结果

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100 项与 Hepatitis B vaccine(Merck Sharp & Dohme) 相关的转化医学

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100 项与 Hepatitis B vaccine(Merck Sharp & Dohme) 相关的专利（医药）

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项与 Hepatitis B vaccine(Merck Sharp & Dohme) 相关的文献（医药）

2025-09-01·CLINICAL TRANSPLANTATION

Hepatitis B Boosters Using a Different Product vs. the Same Product for Kidney Transplant Recipients: A Retrospective Study With Bayesian Inference

Article

作者: Iwata, Kentaro ; Miyake, Hideaki ; Hyodo, Yoji ; Ikegaki, Shunkichi

ABSTRACT:

Objectives:

Hepatitis B vaccination is recommended for those receiving kidney transplants. When hepatitis B surface antibody (HBsAb) levels remain low, the booster dose of the vaccine should be considered. Some consider that the use of a different product as a booster might be beneficial to the patients, but the effectiveness of such a strategy has not been evaluated.

Methods:

The kidney transplant recipients (KTR) who received hepatitis B vaccines (Bimmugen or Heptavax‐II), and failed to develop enough antibody titer and those who received additional vaccines, were enrolled in the study. Those who received a different product were compared with those who received the same product as the booster. The outcome is the seroconversion of hepatitis B surface antibody level ≧ 10 IU/mL.

Results:

A total of 26 patients were non‐responders after a receipt of three‐dose hepatitis B vaccines. Among those, 15 received additional hepatitis B vaccine of the different product (crossover group), and 11 received the same product (non‐crossover group). Only five patients (19.2%) had seroconversion after the booster doses, three in the crossover group (20%) and two in the non‐crossover group (18.2%) (p = 1.0). In the Bayesian analysis, the medial posterior probability of the seroconversion rate of the crossover group was 23% (95% CrI: 7%–47%), whereas that of the non‐crossover group was 14% (95% CrI: 2%–40%).

Conclusion:

The crossover strategy hepatitis B vaccines did not appear to lead to seroconversion of much significance among KTR. Other options to augment the protection should be investigated to protect these populations against the infection.

2024-09-01·CLINICAL TRANSPLANTATION

Hepatitis B Vaccine Compliance, Serologic Response, and Durability in Adult Thoracic Organ Transplant Recipients

Article

作者: Brumble, Lisa M. ; Beam, Elena ; Chiu, Chia‐Yu ; Vikram, Holenarasipur R. ; Watt, Kymberly D. ; Sampathkumar, Priya

ABSTRACT:

Introduction:

Hepatitis B virus (HBV) vaccination is recommended for solid organ transplant (SOT) candidates. However, there is a lack of data on the HBV vaccine compliance, serologic response, and durability of HBV seroprotection in thoracic organ transplantation recipients.

Methods:

We conducted a retrospective study of adult thoracic organ (heart and lung) transplant candidates who received HBV vaccination at Mayo Clinic sites in Minnesota, Arizona, and Florida between January 2018 and August 2023. Conventional recombinant hepatitis B vaccine (Recombivax HB) was used before 2020, and Heplisav‐B was preferred after 2020. HBV seroprotection was defined as hepatitis B surface antibody (HBsAb) ≥ 10 IU/L. Furthermore, we compared characteristics between recipients who maintained HBV seroprotection and those who lost HBV seroprotection (HBsAb < 10 IU/L) at 30 days posttransplantation (D30).

Results:

Among 922 candidates who were eligible for HBV vaccination, 430 (47%) completed the HBV vaccine series. Patients receiving Heplisav‐B were more likely to complete the series than Recombivax HB (81% vs. 60%, p < 0.001) and Heplisav‐B had a higher seroprotection rate than Recombivax HB (75% vs. 64%, p = 0.023). Multivariate logistic regression analysis identified receiving Heplisav‐B as an independent predictor for HBV seroprotection (adjusted odds ratio [aOR] 1.723; 95% confidence interval [CI] 1.056–2.810; p = 0.029). A total of 145 thoracic organ transplant recipients achieved HBV seroprotection at the date of transplantation. Loss of HBV seroprotection occurred in 38 (26%) patients at D30. Multivariate logistic regression analysis identified two predictors for HBV seroprotection loss at D30: age ≥ 60 years (aOR, 2.503; 95% CI 1.026–6.107; p = 0.044), and pretransplant HBsAb level between 10 and 100 IU/L (aOR, 18.575; 95% CI 5.211–66.209; p < 0.001).

Conclusions:

Although less than half of thoracic organ transplant candidates completed HBV vaccine series pretransplant, Heplisav‐B provided a higher vaccine completion rate and seroprotection than the 3‐dose Recombivax HB. Clinicians should also be aware of the increased loss of HBV seroprotection in thoracic organ transplant recipients with age ≥ 60 years and pretransplant HBsAb between 10 and 100 IU/L. Assessment of seroprotection after HBV vaccination should be prioritized during the pretransplant period.

2021-12-01·Vaccine3区 · 医学

Cholecalciferol supplementation to improve the hepatitis B vaccination response in hemodialysis patients: A first randomized open label pilot study (DeVitaHep)

3区 · 医学

Article

作者: Lhotta, Karl ; Rosenkranz, Alexander R ; Zitt, Emanuel ; Schwantzer, Gerold ; Hafner-Giessauf, Hildegard ; Sprenger-Mähr, Hannelore ; Horn, Sabine

BACKGROUND:

Patients with advanced chronic kidney disease should be vaccinated against hepatitis B. In observational studies vitamin D insufficiency is associated with a reduced seroconversion rate. The effect of cholecalciferol supplementation on hepatitis B vaccination response in haemodialysis patients with vitamin D insufficiency is unknown.

METHODS:

In this randomized open label pilot study 40 unvaccinated haemodialysis patients with 25(OH)D insufficiency (<30 ng/mL) were enrolled. In the supplementation group, we administered cholecalciferol orally in a dose of 28,000 IU weekly for a maximum of 12 weeks. Hepatitis B vaccination (HBvaxPRO 40 µg i.m. months 0, 1, 6) was performed after achieving a 25(OH)D level >30 ng/mL or after completing three months of supplementation despite failure to achieve the target level. In the control group, patients were vaccinated immediately after randomization. Anti-hepatitis B-antibody titer (anti-HBs) was measured eight weeks after completing the vaccination course.

RESULTS:

Thirty-seven (26 male, 11 female) patients aged 65 (13.5) years underwent randomization with 17 patients allocated to the control group and 20 patients included in the supplementation group. After 12 weeks of cholecalciferol supplementation, mean (SD) 25(OH)D concentration increased from 15.0 (8.0) to 31.0 (7.1) ng/mL, but remained unchanged in the control group (14.0 (7.1) to 11.6 (7.5) mg/mL). Neither the number of patients with seroconversion (anti-HBs titer ≥ 10 IU/L; n = 6 (35.3%) vs n = 3 (27.3%), p = 0.704), nor the number of patients with seroprotection (anti-HBs titer >100 IU/L; n = 4 (23.5%) vs n = 2 (18.2%) differed between treatment groups. Cholecalciferol supplementation was safe without treatment-related adverse events.

CONCLUSION:

In this small pilot study, high-dose oral cholecalciferol supplementation did not improve the hepatitis B vaccination response in haemodialysis patients with vitamin D insufficiency. This clinical trial was registered within EudraCT (EudraCT number 2011-004621-26).

项与 Hepatitis B vaccine(Merck Sharp & Dohme) 相关的新闻（医药）

2025-12-06

·ETPharma

Vaccine makers raise concerns over US panel's shift away from hepatitis B shots for newborns

Bengaluru: Vaccine makers expressed concern on Friday's decision by a U.S. advisory panel to scrap its long-standing recommendation that all infants receive a hepatitis B vaccine at birth, a shift that public health experts fear will undermine decades of public health advances. Merck, whose Recombivax HB has been a staple of the U.S. childhood immunization program, said it was "deeply concerned" by the decision of the CDC's Advisory Committee on Immunization Practices (ACIP), warning it "puts infants at unnecessary risk of chronic infection, liver cancer and even death." The company said the universal birth dose, which was instituted in 1991, has driven a 99% drop in acute hepatitis B cases in children and young adults and argued there is no evidence that delaying it provides any benefit. Infectious disease experts, as well as organizations representing pediatricians, pharmacists and public health professionals decried the move. Hepatitis B, which can spread from mother to child during birth, can cause severe liver disease and early death, and has no cure. According to the National Foundation for Infectious Diseases, the universal hepatitis B birth dose has prevented more than 500,000 childhood infections, cut infant cases by 95% and averted an estimated 90,100 deaths. Many of the committee members, which were appointed by U.S. Health and Human Services Secretary Robert F. Kennedy Jr., a longtime vaccine skeptic, criticized the vaccine safety data and said that the U.S. vaccine schedule was out of step with other countries, particularly Denmark, that have low hepatitis B rates. GSK said it stands behind the science supporting its vaccine and is awaiting the CDC's formal adoption of the recommendation to assess its impact. Its vaccine, Engerix-B, has been approved since 1989, with 1.4 billion doses administered worldwide. Merck and GSK shares fell about 1% each following the vote. U.S.-listed shares of Sanofi, another maker of hepatitis B shots, rose about 0.7%. The panel now recommends only infants born to mothers who test positive for hepatitis B should receive the birth dose. Parents of infants whose mothers test negative are advised to decide, in consultation with a healthcare provider, when or whether to begin the vaccine series. Merck urged the committee to return liaison organizations and frontline clinicians to its work groups, calling discussions led by medical and scientific experts "essential to informing sound, evidence-based recommendations that safeguard public health." (Reporting by Mrinalika Roy in Bengaluru; Editing by Alan Barona)>

疫苗上市批准

2025-11-25

·生物制品圈

CHO细胞 VS 酵母系统，哪种乙肝疫苗更适合你？

当你接种乙肝疫苗时，是否曾好奇过：这支疫苗是怎么“造”出来的？目前，国内市面上的重组乙肝疫苗看似一样，但它们的“出生地”却大不相同——有的来自酵母细胞，有的则诞生于哺乳动物细胞，如CHO细胞。虽然两者都属于基因重组技术，安全有效，但它们的生产“工厂”不同，表达的抗原结构也有差异。了解这些区别，不仅能帮助我们更科学地认识疫苗，还能在特殊情况下做出更适合自己的选择。今天，我们就来揭开乙肝疫苗背后的“细胞密码”。 01 技术对比：“CHO细胞造”与“酵母造”的差异在说具体的细胞之前，我们先了解什么是重组乙型肝炎疫苗。所谓重组乙型肝炎疫苗（乙肝疫苗，HepB），是通过基因工程技术，将乙肝病毒表面抗原（HBsAg）的基因片段“插入”到其他生物细胞中，经过体外的培养增殖，让这些细胞大量生产HBsAg蛋白，再经纯化、加佐剂后制成疫苗。整个过程不使用活病毒，也不含完整病毒基因组，因此非常安全。（相关阅读：基因重组乙肝疫苗的前世今生——从血源到CHO细胞技术的飞跃）目前，国内市面上的疫苗均属于重组乙肝疫苗，按照表达系统的不同，分为CHO细胞、酿酒酵母、汉逊酵母三种。前者为哺乳动物细胞系统疫苗，后两者统称为酵母系统疫苗。它们的核心区别在于谁来生产抗原。表1：重组乙肝疫苗（CHO细胞）与重组乙肝疫苗（酵母系统）比较 CHO细胞疫苗：高端“生物反应器”，结构更真实 CHO细胞乙肝疫苗是采用基因工程技术将无传染性的HBsAg的S基因片段克隆到载体，用重组载体转染真核生物CHO细胞，通过细胞培养、增殖、分泌出HBsAg到培养液中，收集分泌液，经高速离心、纯化、除菌后，加入佐剂吸附（氢氧化铝）而制成。其中，CHO细胞，即中国仓鼠卵巢细胞（中国仓鼠属于来自于中国北部和蒙古地区的啮齿动物家族），是哺乳动物细胞类，它是基因工程表达系统中最高等的宿生细胞，其表达产物更接近于天然产品。 HBsAg在哺乳动物细胞中通过内质网和高尔基体的加工使其某些氨基酸被糖基化，同时哺乳动物细胞也能够帮助HBsAg蛋白形成二硫键，使其结构更加接近于HBV颗粒的天然结构，提高其免疫原性。当HBsAg在哺乳动物细胞内形成VLP后，主动分泌至细胞外，产生的VLP结构更加完整。我国于1992年研制成功重组CHO细胞乙肝疫苗。实际上，在目前的药物开发中，CHO细胞备受推崇，其不仅被用于一些疫苗的生产，如乙肝疫苗、带状疱疹疫苗、呼吸道合胞病毒（RSV）疫苗等；还被用于生产多种蛋白质药物，如单克隆抗体、重组蛋白、生长因子等；此外，其还是细胞工程和基因编辑的重要工具。作为生物制药行业中重组蛋白生产的主力军，超过70%的重组治疗性蛋白都是用CHO细胞表达系统生产的。另外，有数据统计显示，截至2025年1月，全球范围内一共有191种抗体类药物(不完全统计)被至少一个药品监管机构批准上市，在众多上市的抗体药物中，CH0细胞表达系统占75.9%。可见，CHO细胞被广泛应用于药物开发中。优点糖基化修饰：CHO细胞能对HBsAg进行准确的糖基化，使其空间结构更接近天然病毒，免疫原性更强，诱导人体产生抗体速度快、滴度高、持续时间长；天然组装：HBsAg可主动分泌至细胞外，自组装成完整的病毒样颗粒（VLP），结构更完整；适用人群广泛：对酵母成分过敏者或免疫应答较弱的人群也适用。局限培养条件复杂，成本较高；生产周期较长，产能相对有限。酵母系统疫苗：高效“工厂”，成本低酵母系统乙肝疫苗是通过在酵母细胞（酿酒酵母或汉逊酵母）中表达S蛋白制造而成，在酵母细胞中表达、纯化后，HBsAg能够自主组装折叠为一种无毒性的颗粒物质，也就是VLP，其作为疫苗能够在机体内对HBV的感染产生特异保护性免疫。值得注意的是，我国首款酵母源性乙肝疫苗是通过引进默克的技术后才制备上市的。1995年，我国引进美国默沙东公司的重组酿酒酵母乙肝疫苗生产工艺，生产重组酵母乙肝疫苗。2004年，重组汉逊酵母乙肝疫苗也在我国获批上市使用。图1：酵母表达系统 (Sookhoo, et al., 2024) 优点生产效率高：酵母生长快，发酵周期短；成本低：适合大规模工业化生产；工艺成熟：全球应用广泛。局限无法对HBsAg进行糖基化修饰，抗原结构与天然病毒略有差异； HBsAg在细胞内积累，需裂解细胞才能提取，再通过体外组装形成病毒样颗粒（VLP）；少数人可能对残留的酵母蛋白过敏。总的来说，这两类重组乙肝疫苗有各自的优势和局限性。 02 如何选择？听从专业建议，按需选择据《慢性乙型肝炎防治指南（2022年版）》建议，接种乙型肝炎疫苗是预防HBV感染最有效的方法。乙型肝炎疫苗的接种对象主要是新生儿，其次为婴幼儿、15岁以下未免疫人群和成年高危人群。而据2024年的《成人乙型肝炎疫苗接种专家建议》中显示，感染HBV的高危人群包括器官移植患者、经常接受输血或血液制品人员、免疫功能低下者、职业易发生外伤者、HBsAg阳性者家庭成员、糖尿病患者、肾透析患者、HIV感染者、慢性肝病患者、男男同性性行为者和多个性伴侣者、注射毒品者等。另外，该专家建议还明确建议：所有18-59岁无乙肝疫苗接种史和HBV感染史者应接种乙肝疫苗；有感染HBV高风险因素的≥60岁成人应接种乙肝疫苗；无感染HBV高风险因素的≥60岁成人可接种乙肝疫苗。总的来说，乙肝疫苗推荐接种人群为未接种或未全程接种乙肝疫苗或接种史不详者，尤其是高风险人群。至于选择哪类乙肝疫苗比较好，首先明确：无论是CHO细胞系统还是酵母系统，我国批准上市的乙肝疫苗均安全、有效，都能提供良好的保护。不过，以下情况可考虑优先选择CHO细胞疫苗：母婴阻断：20μgCHO细胞乙肝疫苗是唯一可用于新生儿母婴阻断的大剂量乙肝疫苗；且全年龄组都可使用；对酵母成分过敏者：如接种酵母疫苗后出现严重过敏反应，可选择无酵母蛋白的CHO细胞疫苗；免疫功能低下人群：如老年人、慢性病患者等，CHO细胞疫苗可能激发更强免疫应答；追求更高结构相似性者：希望抗原更接近天然病毒，可选择CHO细胞技术路线。追求快速且持久的抗体保护者:有数据显示，CH0细胞乙肝疫苗接种后最快8天可产生抗体；长期免疫效果观察显示，目前其最长保护时间已达26年。值得注意的是，目前我国重组乙肝疫苗（CHO细胞）为华北制药金坦生物独家供应。自1993年与中国预防医学科学院病毒学研究所（现中国疾病预防控制中心病毒病研究所）达成合作、1997年正式成立专业化生产平台后，该公司通过持续的工艺优化（如2010年去除硫柳汞并增加预灌封注射器包材、2020年升级包装材料为中硼西林瓶）和产能扩张，逐步成为国内重组乙肝疫苗（CHO细胞）的独家规模化生产企业。据了解，华北制药金坦生物的乙肝疫苗产品线（含西林瓶与预灌封注射器）已实现全国31个省市自治区的全面覆盖，渗透率达80%以上的区县疾控中心，市场根基深厚。截至目前，该疫苗累计销量已突破2亿剂次，是推动我国乙肝防控的重要力量。 03 结语：技术多样，选择多元 “酵母造”与“细胞造”并非“谁优谁劣”，而是不同技术路线的互补，各有特点。酵母疫苗保障了大规模、低成本的供应；CHO细胞疫苗则在结构真实性、免疫原性方面具有独特优势。因此，我们在选择疫苗时，无需过度纠结，按需选择即可。而了解这些知识，有助于在特殊情况下做出更科学的选择。无论是哪种技术，最终目标都是为了守护健康，预防乙肝。参考资料： [1]尤红,王福生,李太生,等.慢性乙型肝炎防治指南(2022年版)[J].实用肝脏病杂志,2023,26(03):457-478. [2]崔富强,杜娟,方钟燎,等.成人乙型肝炎疫苗接种专家建议[J].临床肝胆病杂志,2024,40(08):1551-1556. [3]《当代新疫苗（第二版）》第9章、第31章. [4]⌈原创好文⌋认识CHO细胞.长睿生物.2023-09-20. [5]酵母表达系统：撬动重组蛋白产业化的"黄金支点".北京安必奇生物科技有限公司.2025-03-03. [6]从北京到世界: CHO细胞的前世今生.生物制品圈.2023-12-17. [7]LiuH, LiL, Li y, LiuM, Song Y, DingF, zhang X, Li J. Vaginal Delivery andBreastfeeding Benefit Infant Immune Response to Hepatitis B Vaccine: A ProspectiveCohort Study. 」 clin Transl Hepatol. 2023 Aug 28, 11 (4):899-907. doi:10.14218/JCTH,2022.00032S.Epub 2023 Mar 7.PMID:37408801;PHC:PHC10318287. [8]苏秋东,郝志勇,邱丰,等。重组 CH0乙型肝炎疫苗长期免疫效果评价:正定县监测点 26年跟踪研究[J1.中华实验和临床病毒学杂志,2025,39(04)434-440.D0I:10.3760/aa j.m112866-20250226-00044 [9]CHO细胞培养基：重组蛋白工业化生产的关键技术.Lonza Bioscience.2025年2月12日. [10]全球已上市抗体类药物的表达系统全信息汇总.大轮明王.2025年2月7日. 识别微信二维码，添加生物制品圈小编，符合条件者即可加入生物制品微信群！请注明：姓名+研究方向！版权声明本公众号所有转载文章系出于传递更多信息之目的，且明确注明来源和作者，不希望被转载的媒体或个人可与我们联系(cbplib@163.com)，我们将立即进行删除处理。所有文章仅代表作者观不本站。

疫苗

2025-11-23

·生物制品圈

类病毒样颗粒（VLP）：一种多功能且高效的疫苗平台

摘要：传统减毒或灭活疫苗存在复制失控、免疫原性不足、生产复杂等问题，而病毒样颗粒（VLPs）作为新型疫苗平台，凭借 “模仿病毒却无感染性” 的特性脱颖而出。本文通俗解读 VLPs 的结构优势、生产方式，以及已获批的乙肝、HPV、疟疾等 VLPs 疫苗的效果，还有正在研发的 RSV、诺如病毒等 VLPs 疫苗进展，让你看懂这款 “万能疫苗平台” 的潜力。一、疫苗界的 “高仿选手”：VLPs 到底是什么？我们先搞懂核心：病毒样颗粒（VLPs）是由病毒结构蛋白自组装形成的 “高仿病毒”—— 它长得和真实病毒几乎一模一样，大小、表面结构、电荷特性都高度相似，却少了最关键的 “核心”：病毒基因组。这就意味着，VLPs 既保留了病毒能被免疫系统识别的 “特征”，又完全没法复制、不会致病，对比传统减毒活疫苗（有突变返毒风险）、灭活疫苗（免疫原性弱），安全性直接拉满。更妙的是，VLPs 的尺寸大多在 20-200 纳米，和天然病毒一致，能快速进入淋巴系统，还能和巨噬细胞、树突状细胞等抗原呈递细胞高效结合，激活 T 细胞和 B 细胞，触发强免疫反应。而且 VLPs 表面有规律排列的抗原表位（间隔 5-10 纳米），刚好是激活 B 细胞的 “黄金间距”；内部还能包裹佐剂（比如 Toll 样受体配体），进一步增强免疫效果。甚至可以做成 “嵌合 VLPs”—— 把不同病毒的蛋白嵌进去，一针防多种病，灵活性拉满。图1 病毒样颗粒（VLPs）及嵌合病毒样颗粒生成流程（注：原图展示了普通 VLPs 的构建过程 —— 从克隆病毒衣壳蛋白基因、转入表达系统，到蛋白自组装形成 VLPs；同时呈现了嵌合 VLPs 的构建 —— 在衣壳蛋白基因中插入外源肽基因，最终生成携带外源抗原的嵌合颗粒，如疟疾 VLPs 疫苗中疟原虫蛋白与乙肝表面抗原的融合设计）二、VLPs 是怎么 “造” 出来的？不同生产线各有千秋想让 VLPs 大规模量产，得选对 “生产车间”，目前主流的表达系统有 5 种，各有优劣：细菌系统：成本低、产量高、易放大，适合做简单的 VLPs（比如仅含 1-2 种结构蛋白），但没法给蛋白做糖基化修饰，可能影响免疫原性，还得控制内毒素含量。酵母/昆虫细胞系统：产量和细菌差不多，能做简单糖基化修饰，HPV 疫苗 Gardasil 9（酵母）、Cervarix（昆虫细胞）都是这么做的；但酵母需要裂解细胞提取 VLPs，昆虫细胞易被杆状病毒污染。哺乳动物细胞系统：能做最复杂的蛋白修饰，适合生产结构复杂的 VLPs（比如乙肝疫苗 PreHevbrio、基孔肯雅热疫苗 Vimkunya），但成本高、产量低。植物细胞系统：低成本、易放大，新冠 VLPs 疫苗 Covifenz 就是用烟草属植物生产的，不过同样没法做复杂糖基化。下表清晰总结了各表达系统的优缺点：表1 病毒样颗粒生产常用表达系统的优劣势三、已落地的 VLPs 疫苗：从乙肝到 HPV，保护力又稳又久目前已有多款 VLPs 疫苗通过审批并广泛应用，下表汇总了这些疫苗的适用疾病、生产系统、获批时间、保护效果等关键信息，能让大家快速 get 各款疫苗的核心优势：表 2 已获批病毒样颗粒疫苗关键信息汇总乙肝 VLPs 疫苗：最早的 VLPs 疫苗之一，Recombivax HB、Engerix-B 三针接种后，婴幼儿保护率接近 100%，抗体能持续 30 年；新一代 Heplisav-B 只需两针，40-55 岁人群保护率达 96.9%，PreHevbrio 则针对老年人优化，65 岁以上人群保护率 83.6%，远超传统疫苗。 HPV VLPs 疫苗：堪称 VLPs 的 “代表作”。二价 Cervarix 防 HPV16/18（致 70% 宫颈癌），保护率 90.4%；四价 Gardasil 额外防 HPV6/11（致 90% 生殖器疣），保护率 100%；九价 Gardasil 9 覆盖 9 种 HPV，防 90% 宫颈癌，抗体能持续 10 年以上，部分国家已简化为 1-2 针接种。疟疾 VLPs 疫苗：Mosquirix 把疟原虫蛋白嵌在乙肝 VLPs 上，解决了单一抗原免疫原性差的问题，儿童接种后保护率 36.3%；新一代 R21/Matrix-M 优化了抗原密度，保护率提升到 68%-75%。基孔肯雅热 VLPs 疫苗：2025 年刚获批的 Vimkunya，单针接种后 12-65 岁人群保护率达 98%，65 岁以上也有 76%，不良反应仅为注射部位疼痛、乏力等轻微症状。下图是已获批 VLPs 疫苗的时间线，能直观看到这款技术的发展速度：图2 病毒样颗粒疫苗获批时间线（注：原图展示了 1981-2025 年获批的 VLPs 疫苗，包括乙肝 Recombivax HB（1986）、HPV Gardasil（2006）、疟疾 Mosquirix（2015）、新冠 Covifenz（2022）、基孔肯雅热 Vimkunya（2025）等）四、未来可期：正在研发的 VLPs 疫苗，瞄准更多 “难缠” 疾病 VLPs 的潜力远不止于此，多款候选疫苗已进入临床后期： RSV/人偏肺病毒（hMPV）疫苗：IVX-A12 把 RSV 和 hMPV 的融合蛋白嵌进人工设计的 VLPs，给 60 岁以上老人接种后，RSV 中和抗体提升 6 倍，hMPV 提升 4 倍，有望解决老年人呼吸道感染难题。诺如病毒疫苗：二价 VLPs 疫苗 rNV-2 v 能诱导交叉免疫，覆盖更多诺如毒株，有望应对每年 20 万诺如相关死亡。脊髓灰质炎疫苗：VLPs 脊髓灰质炎疫苗能避免减毒活疫苗的 “疫苗衍生病毒” 风险，助力彻底消灭脊灰。五、VLPs vs mRNA 疫苗：各有优势，未来互补新冠疫情让 mRNA 疫苗火遍全球，但 VLPs 也有不可替代的优势： mRNA 疫苗研发快，但生产成本高、需超低温储存，在低收入国家推广难；VLPs 生产成本低、常温稳定，运输和储存更友好。 VLPs 免疫原性强，低剂量就能触发强保护，还能诱导持久的 IgG1 抗体；而反复接种 mRNA 疫苗可能导致 IgG4 抗体占比升高，影响长期保护力。当然，两者不是竞争关系 —— 未来结合 AI 设计 VLPs 抗原、优化生产工艺，VLPs 有望和 mRNA 疫苗互补，成为全球免疫计划的核心力量。结语从乙肝到基孔肯雅热，从已获批到研发中的 RSV、诺如疫苗，病毒样颗粒（VLPs）用 “模仿病毒却不致病” 的特性，解决了传统疫苗的诸多痛点。它的灵活性、安全性和持久保护力，让这款平台成为疫苗研发的 “万能选手”。随着生产工艺优化、多价疫苗研发推进，VLPs 不仅能应对已知传染病，还可能拓展到癌症免疫治疗等领域，真正成为守护人类健康的 “硬核武器”。

100 项与 Hepatitis B vaccine(Merck Sharp & Dohme) 相关的药物交易

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外链

KEGG	Wiki	ATC	Drug Bank
-	-	J07BC01	-

研发状态

10 条最早获批的记录,

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适应症	国家/地区	公司	日期
丁型肝炎	欧盟	Merck Sharp & Dohme BV	2001-04-27
丁型肝炎	冰岛	Merck Sharp & Dohme BV	2001-04-27
丁型肝炎	列支敦士登	Merck Sharp & Dohme BV	2001-04-27
丁型肝炎	挪威	Merck Sharp & Dohme BV	2001-04-27
乙型肝炎	美国	Merck & Co., Inc.	1986-07-23

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临床结果

适应症

分期

评价

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研究	分期	人群特征	评价人数	分组	结果	评价	发布日期


NCT04490499 (V419-013, CTgov)	临床3期	乙型肝炎	207	HBVAXPRO™	窪醖簾淵願憲淵壓窪獵 = 鏇夢膚鏇範鹹獵網願簾製範遞繭淵膚選衊鑰夢 (遞積願顧觸鬱鹹選願遞, 選鏇壓觸簾襯艱鏇衊糧 ~ 齋壓鬱範積顧衊壓襯襯) 更多	-	2021-09-05
NCT02429583 (CTgov)	临床4期	丙型肝炎 \| 慢性丙型肝炎	24	Recombivax (Recombivax in HCV Infected Individuals)	鹽網製築淵鹹齋膚觸夢(鏇衊繭夢鹽蓋製齋廠獵) = 齋廠獵廠願網膚憲築衊鏇選獵糧廠顧範獵顧艱 (顧獵鹽襯艱廠製鹽襯鬱, 顧鏇壓淵繭鬱鹽觸築淵 ~ 壓齋壓簾糧鏇醖糧醖製) 更多	-	2020-03-04
				Recombivax (Recombivax in Healthy Volunteers)	鹽網製築淵鹹齋膚觸夢(鏇衊繭夢鹽蓋製齋廠獵) = 觸築繭繭築築醖鬱鬱糧鏇選獵糧廠顧範獵顧艱 (顧獵鹽襯艱廠製鹽襯鬱, 遞構糧憲網鏇糧獵膚蓋 ~ 築鏇夢範願憲襯簾廠範) 更多
NCT01251276 (Pubmed \| Hum Vaccin Immunother)	临床3期	-	204	HBvaxPRO®	糧鑰鹽夢積鹹簾範獵醖(積積鏇鑰窪膚鏇夢齋簾) = 選獵艱繭願鹽餘鏇壓鑰範製壓選衊窪遞願鏇鬱 (壓鑰壓餘鹽糧鬱築遞廠, 34.8 ~ 56.4)	-	2015-01-01
				hepatitis B vaccine (Engerix B™)	糧鑰鹽夢積鹹簾範獵醖(積積鏇鑰窪膚鏇夢齋簾) = 糧構艱簾淵襯鬱夢獵憲範製壓選衊窪遞願鏇鬱 (壓鑰壓餘鹽糧鬱築遞廠, 48.6 ~ 68.5)
NCT00440297 (Pubmed \| Vaccine)	临床3期	-	276	recombinant hepatitis B vaccine (mpHBV)	簾淵選範衊憲齋願窪願(鹽願鬱選繭鹹鏇廠積網) = 築壓網範蓋鑰鬱憲鹹廠選壓觸鬱選繭廠築觸衊 (鑰襯襯憲築築鏇壓艱鹽, 15.7 ~ 48.0) 更多	-	2014-11-12
				Licensed hepatitis B vaccine	簾淵選範衊憲齋願窪願(鹽願鬱選繭鹹鏇廠積網) = 窪繭獵製遞積製淵齋鏇選壓觸鬱選繭廠築觸衊 (鑰襯襯憲築築鏇壓艱鹽, 28.7 ~ 82.7) 更多
NCT01463683 (V232-062, CTgov)	临床3期	乙型肝炎	722	2XP HEPTAVAX™-II SC (V232-2XP SC)	糧鹽簾構繭築觸夢齋積 = 遞夢艱繭顧襯選襯選繭糧艱餘夢淵簾廠糧選壓 (獵積積鏇觸窪願築願遞, 壓憲餘願繭憲觸衊鹹觸 ~ 憲襯鏇積鏇夢繭製蓋窪) 更多	-	2014-02-17
				HEPTAVAX™-II (V232-1XP SC)	糧鹽簾構繭築觸夢齋積 = 製蓋製製網範淵遞簾簾糧艱餘夢淵簾廠糧選壓 (獵積積鏇觸窪願築願遞, 鑰簾膚壓餘夢鹽簾範艱 ~ 簾廠蓋構範鬱遞觸醖淵) 更多
NCT00322361 (Pubmed \| Vaccine)	临床2期	新生儿感染	566	modified process hepatitis B vaccine (mpHBV)	鑰鬱壓願觸觸遞製鏇顧(鹽壓膚製網膚鏇鏇顧繭) = 憲築網鑰鬱積襯構範鑰淵獵顧觸夢網蓋齋壓餘 (網壓繭齋積觸淵獵廠齋 ) 更多	不佳	2012-02-14
				Control vaccine	鑰鬱壓願觸觸遞製鏇顧(鹽壓膚製網膚鏇鏇顧繭) = 夢願憲積膚壓膚餘夢衊淵獵顧觸夢網蓋齋壓餘 (網壓繭齋積觸淵獵廠齋 ) 更多
NCT00440531 (Pubmed)	临床3期	-	538	hepatitis B vaccine (mpHBV)	糧鏇構顧蓋齋鏇壓製壓(鏇繭鑰獵齋膚醖網築憲) = There were 6 non-vaccine related serious adverse events reported 壓顧衊壓網繭遞網積願 (窪顧窪壓積鹹淵蓋簾淵 )	-	2011-12-01
				hepatitis B vaccine (RECOMBIVAX-HB)
NCT00414050 (Pubmed \| Pediatr Infect Dis J)	临床3期	-	1,718	5 μg mpHBV	遞夢餘醖獵廠構遞襯衊(網膚鬱餘襯遞遞觸願鏇) = 鹹壓糧鑰鏇醖顧壓觸蓋願顧壓艱願簾鑰艱鬱選 (構襯願範衊糧積遞鑰簾, 672.0 ~ 833.1) 更多	-	2011-07-01
				10 μg mpHBV	遞夢餘醖獵廠構遞襯衊(網膚鬱餘襯遞遞觸願鏇) = 廠鹹膚憲鑰窪壓觸廠膚願顧壓艱願簾鑰艱鬱選 (構襯願範衊糧積遞鑰簾, 891.0 ~ 1081.2) 更多
NCT00393523 (V232-058, CTgov)	临床3期	乙型肝炎	1,478	Hepatitis B Vaccine (Modified Process Hepatitis B Vaccine Booster (Group 1))	選齋製選鹽淵積築鏇廠 = 願觸鏇餘廠鏇顧範鹹膚選壓淵壓淵簾簾齋憲艱 (繭夢糧膚簾鏇餘範獵積, 鬱選鑰鹽夢艱簾觸積糧 ~ 淵鏇膚願選鬱鏇餘製膚) 更多	-	2009-10-12
				ENGERIX-B+RECOMBIVAX-HB (ENGERIX-B™ Booster (RECOMBIVAX-HB™ in Infancy) (Group 2))	選齋製選鹽淵積築鏇廠 = 壓壓繭獵選構夢壓鬱齋選壓淵壓淵簾簾齋憲艱 (繭夢糧膚簾鏇餘範獵積, 鑰壓醖醖夢鬱獵鏇簾齋 ~ 築顧顧積壓顧簾鬱簾艱) 更多
NCT00440297 (V232-060, CTgov)	临床3期	乙型肝炎	277	hepatitis B vaccine	遞窪壓餘壓築簾淵選範 = 觸蓋窪淵鏇鑰顧膚齋簾鑰願餘醖鬱憲簾觸憲窪 (構構範構繭艱選網積蓋, 觸築齋獵膚鏇夢齋選構 ~ 觸鹽範鏇積鹽衊襯餘憲) 更多	-	2009-07-08