Innovation: Dual-Function mRNA Platform
创新:攻防兼备的mRNA疫苗
World's first dual-function mRNA vaccine: Prevention + Treatment
全球首创"攻防兼备"预防+治疗双效mRNA疫苗
Reverse Vaccinology Approach
反向疫苗学设计
Predicted novel protective antigens from 2,700 S. aureus genes using bioinformatics. Identified conserved epitopes across clinical isolates.
从2700个金葡菌基因中利用生物信息学预测全新保护抗原,鉴定临床分离株之间的保守表位。
Comprehensive Immune Response
综合免疫应答
Incorporates both humoral (antibody) and cellular (T-cell) immunity antigens. Overcomes limitations of single-epitope approaches.
包含体液免疫和细胞免疫抗原,克服单表位方法的局限性。
Immune Imprinting Solution
免疫印迹突破
mRNA vaccine platform is NOT affected by previous S. aureus exposure - solves the fundamental problem that caused Merck V710 Phase III failure.
mRNA疫苗不受既往金葡菌暴露影响 - 解决导致Merck V710 III期失败的根本问题。
Experiment 1: MRSA Prevention in Mice
实验1:小鼠MRSA预防模型
Study Design
研究设计
Model: Intraperitoneal MRSA infection
Groups: 3 mRNA vaccine designs vs PBS control
Schedule: Day 0 (prime) → Day 21 (boost) → Day 35 (challenge)
Assessment: Bacterial burden in blood, peritoneal fluid, spleen
模型:小鼠腹腔MRSA感染
分组:3种mRNA疫苗设计 vs PBS对照
免疫:D0初免 → D21加强 → D35攻毒
检测:血液、腹腔液、脾脏载菌量
3
Vaccine formulations tested
疫苗设计版本
100%
Protection rate (vaccinated)
疫苗接种组保护率
10-100x
Bacterial load reduction
载菌量降低倍数
Result: All three vaccine-immunized groups showed significantly reduced bacterial burden in blood, peritoneal fluid, and spleen compared to PBS controls. Multi-organ protection confirmed.
结果:所有疫苗免疫组血液、腹腔液、脾脏载菌量均显著低于PBS对照组。多器官保护得到证实。
Experiment 2: Overcoming Immune Imprinting
实验2:免疫印迹突破
The Immune Imprinting Problem
免疫印迹问题背景
Previous exposure to S. aureus creates "immune imprinting" - the immune system fails to mount effective response to new vaccine antigens. This is why Merck V710 failed in Phase III (patients with prior S. aureus exposure showed no benefit).
既往金葡菌暴露会产生"免疫印迹"现象 - 免疫系统对新疫苗抗原无法产生有效应答。这是Merck V710 III期失败的原因(曾暴露于金葡菌的患者无获益)。
Study Design
研究设计
Pre-sensitization: Day -28, -21, -14: sub-lethal MRSA infection to establish immune imprinting
Vaccination: Day 0, 21 (after pre-sensitization established)
Challenge: Day 35: lethal MRSA dose
Comparison: Pre-sensitized vaccine group (M) vs non-sensitized vaccine group (O)
预感染:D-28、-21、-14:亚致死低剂量感染建立免疫印迹
疫苗接种:D0、21(预感染后)
攻毒:D35:致死剂量MRSA
对比:预感染疫苗组(M) vs 未预感染疫苗组(O)
3
Pre-challenge exposures
预感染次数
M vs O
Comparison groups
对比分组
No Difference
Protection rate
保护率相同
Critical Finding: Pre-sensitized vaccine group (M) showed NO SIGNIFICANT DIFFERENCE in protection compared to non-sensitized vaccine group (O). mRNA vaccine efficacy is NOT diminished by prior S. aureus exposure. This proves the vaccine overcomes immune imprinting - solving the V710 problem.
关键发现:预感染疫苗组(M)与未预感染疫苗组(O)的保护效果无显著差异。mRNA疫苗不受既往金葡菌暴露影响。这证明疫苗解决了免疫印迹问题 - 破解V710失败原因。
Experiment 3: Chronic Osteomyelitis (Biofilm Penetration)
实验3:慢性骨髓炎模型(生物膜穿透)
Clinical Significance
临床意义
Chronic osteomyelitis is called "the cancer of orthopedics" - S. aureus forms biofilms in bone that are resistant to antibiotics. This is one of the most challenging infection types to treat.
慢性骨髓炎被称为"骨科的癌症" - 金葡菌在骨内形成生物膜,对抗生素耐受。这是最具挑战性的感染类型之一。
Study Design
研究设计
Model: Chronic bone marrow infection with biofilm
Treatment arms: mRNA vaccine vs Vancomycin (gold-standard antibiotic)
Mechanism: Evaluate immune cell infiltration and biofilm clearance
Outcome: Bacterial clearance and bone healing
模型:慢性骨髓炎生物膜感染
治疗组:mRNA疫苗 vs 万古霉素(金标准抗生素)
机制:评估免疫细胞浸润和生物膜清除
结果:细菌清除和骨愈合
100%
Immune infiltration (vaccine)
免疫浸润率
Complete
Bacterial eradication
细菌清除
Result: mRNA vaccine-immunized animals showed complete immune cell infiltration into bone marrow and complete S. aureus eradication despite biofilm presence. This suggests vaccines can treat established infections - a major advantage over antibiotics alone.
结果:疫苗免疫组免疫细胞可完全浸润骨髓,彻底清除金葡菌。这表明mRNA疫苗可治疗已建立的感染 - 相比单纯抗生素具有重大优势。
Experiment 4: Pig Field Trial (Head-to-Head vs Antibiotics)
实验4:病猪临床试验(与抗生素头对头对比)
Translational Study
转化研究
Large animal model to evaluate vaccine efficacy in naturally infected animals with therapeutic potential assessment.
大动物模型评估自然感染动物中疫苗疗效和治疗潜力。
Study Parameters
研究参数
Vaccine group: 6 diseased pigs
Control group: 5 diseased pigs treated with conventional antibiotics + Chinese medicine
Vaccination: 50 μg/pig/dose, intramuscular (neck), Days 0/4/7/14/28
Assessment: Clinical symptoms, recovery timeline, treatment efficacy
疫苗组:6头病猪
对照组:5头病猪(抗生素+中药治疗)
免疫方案:50μg/头/次,颈部肌注,D0/4/7/14/28
评估:临床症状、恢复时间、疗效
6 vs 5
Vaccine vs antibiotic pigs
疫苗组vs对照组
5 doses
Immunization schedule
免疫次数
7-10 days
Therapeutic onset (vaccine)
疗效出现时间
Result: Vaccine-treated pigs demonstrated significant clinical improvement by days 7-10, with symptom improvement trajectory trending MORE FAVORABLY than the antibiotic-treated control group. This demonstrates therapeutic efficacy in naturally infected large animals.
结果:疫苗组病猪在第7-10天显示显著临床改善,症状改善趋势比抗生素对照组更明显。证明了自然感染大动物中的治疗效果。