Choi Eun-Sun, Pyo Seong-Wook, Kim So-Hyeon, Jeon Jun-Ho, Rhie Gi-Eun, Yun Mi-Ran, Yi Hwajung, Chung Yoon-Seok
Division of High-Risk Pathogens, Department of Laboratory Diagnosis and Analysis, Korea Disease Control and Prevention Agency, KDCA, Cheongju 28159, Republic of Korea.
Division of Infectious Disease Diagnosis, Chungcheong Regional Center for Disease Control and Prevention, Korea Disease Control and Prevention Agency, KDCA, Cheongju 28159, Republic of Korea.
Vaccines (Basel). 2025 Jan 6;13(1):39. doi: 10.3390/vaccines13010039.
Botulinum neurotoxins (BoNTs), produced by , are potent protein toxins that can cause botulism, which leads to death or neuroparalysis in humans by targeting the nervous system. BoNTs comprise three functional domains: a light-chain enzymatic domain (LC), a heavy-chain translocation domain (HC), and a heavy-chain receptor-binding domain (HC). The HC domain is critical for binding to neuronal cell membrane receptors and facilitating BoNT internalization via endocytosis. Accordingly, it may serve as a vaccine candidate, inducing anti-BoNT-neutralizing antibodies in animals. Here, we aimed to develop a vaccine capable of simultaneously defending against both BoNT/A and B.
We combined the HC domains of botulinum neurotoxin type A (BoNT/A) and botulinum neurotoxin type B (BoNT/B) in to produce a recombinant protein (rHCB-L-HCArHCcB) that offers dual protection against both toxins by inhibiting their receptor binding. To evaluate the efficacy of the vaccine, mice were immunized intramuscularly with rHCB-L-HCA plus alum thrice at 2-week intervals, followed by the assessment of immunogenicity and protective efficacy.
The antibody titer in mice immunized with rHCB-L-HCA was significantly higher than that in mice immunized with alum alone, protecting them from the lethal challenges of BoNT/A (10 50% lethal dose, LD) and B (10 LD).
These findings suggest that rHCB-L-HCA may simultaneously be an effective vaccine candidate against BoNT/A and B.
肉毒杆菌神经毒素（BoNTs）由肉毒杆菌产生，是一种强效蛋白质毒素，可导致肉毒中毒，通过靶向神经系统致使人类死亡或神经麻痹。BoNTs包含三个功能结构域：轻链酶结构域（LC）、重链转位结构域（HC）和重链受体结合结构域（HC）。HC结构域对于与神经元细胞膜受体结合以及通过内吞作用促进BoNT内化至关重要。因此，它可作为候选疫苗，在动物体内诱导抗BoNT中和抗体。在此，我们旨在研发一种能够同时抵御BoNT/A和BoNT/B的疫苗。
我们将A型肉毒杆菌神经毒素（BoNT/A）和B型肉毒杆菌神经毒素（BoNT/B）的HC结构域组合在一起，以产生一种重组蛋白（rHCB-L-HCArHCcB），该重组蛋白通过抑制毒素与受体的结合，对两种毒素都提供双重保护。为评估该疫苗的疗效，将小鼠每隔2周肌肉注射rHCB-L-HCA加明矾三次，随后评估免疫原性和保护效果。
用rHCB-L-HCA免疫的小鼠体内抗体滴度显著高于仅用明矾免疫的小鼠，保护它们免受BoNT/A（10倍50%致死剂量，LD）和BoNT/B（10倍LD）的致死性攻击。
这些发现表明，rHCB-L-HCA可能同时是一种针对BoNT/A和BoNT/B的有效候选疫苗。
