Mardani Rajab, Bahmanje Anahita, Kazeroni Yousef Cheraghi, Khoshroo Fereydoon, Roshanaie Bahram, Sadeghche Tahereh, Pajaie Kourosh, Hosseini Seyed Nezamedin, Doroud Delaram, Shahali Maryam
Department of Viral Vaccines Production, Research and Production Complex, Pasteur Institute of Iran, Tehran, Iran.
Department of Quality Control, Research and Production Complex, Pasteur Institute of Iran, Tehran, Iran.
Chonnam Med J. 2025 May;61(2):84-89. doi: 10.4068/cmj.2025.61.2.84. Epub 2025 May 23.
Rabies continues to pose a serious public health threat worldwide, with vaccination being the most effective means of prevention. However, commercially available inactivated rabies vaccines often require multiple doses and lack potent adjuvants to enhance their efficacy. This study aimed to investigate the coupling of whole inactivated rabies virus to mannan under oxidizing conditions to improve immune responses against a standard rabies vaccine. We explored the conjugation of whole inactivated rabies virus with oxidized mannan (Rab-OxMan) to enhance immune responses. Mice were immunized intraperitoneally with 350 µg of the Rab-OxMan formulation on days 1 and 7. Two weeks after immunization, serum samples were collected to measure levels of IgG, IgM, and TNF-α using ELISA. The vaccine's potency was also evaluated using the National Institutes of Health (NIH) assay. Our findings showed a significant increase in IgG levels and a decrease in IgM levels in the Rab-OxMan group compared to the Alum-adjuvanted vaccine group (p<0.05). Additionally, TNF-α levels were notably higher in the Rab-OxMan group (p<0.05). Statistical analysis revealed that IgG levels had the highest sensitivity and specificity, with a significant correlation between the measured variables. Importantly, the Rab-OxMan formulation provided 1.8 times greater protection in challenge tests compared to the alum-adjuvanted group. This study is the first to demonstrate that oxidized mannan can serve as a novel adjuvant for veterinary rabies vaccines. The results highlight significant improvements in the immunogenicity and efficacy of rabies vaccines, suggesting a promising strategy for enhancing rabies prevention and potentially reducing the incidence of this deadly disease.
狂犬病在全球范围内仍然对公共卫生构成严重威胁，接种疫苗是最有效的预防手段。然而，市售的灭活狂犬病疫苗通常需要多剂接种，并且缺乏有效的佐剂来增强其效力。本研究旨在探讨在氧化条件下将全灭活狂犬病病毒与甘露聚糖偶联，以改善针对标准狂犬病疫苗的免疫反应。我们探索了全灭活狂犬病病毒与氧化甘露聚糖（Rab-OxMan）的偶联，以增强免疫反应。在第1天和第7天，给小鼠腹腔注射350μg的Rab-OxMan制剂。免疫两周后，收集血清样本，使用酶联免疫吸附测定法（ELISA）测量IgG、IgM和肿瘤坏死因子-α（TNF-α）的水平。还使用美国国立卫生研究院（NIH）的检测方法评估了疫苗的效力。我们的研究结果表明，与铝佐剂疫苗组相比，Rab-OxMan组的IgG水平显著升高，IgM水平降低（p<0.05）。此外，Rab-OxMan组的TNF-α水平明显更高（p<0.05）。统计分析表明，IgG水平具有最高的敏感性和特异性，测量变量之间存在显著相关性。重要的是，在攻毒试验中，Rab-OxMan制剂提供的保护作用是铝佐剂组的1.8倍。本研究首次证明氧化甘露聚糖可作为兽用狂犬病疫苗的新型佐剂。结果突出了狂犬病疫苗免疫原性和效力的显著改善，表明这是一种增强狂犬病预防并可能降低这种致命疾病发病率的有前景的策略。
