Hu Ruirui, Zhang Qianyi, Wang Wenjia, Ren Wenhao, Yao Mengxin, Xu Yimei, Zhang Hui, Sheng Jinliang, Wang Yong, Chen Chuangfu, Ma Zhongchen
College of Animal Science and Technology, Shihezi University, Shihezi, Xinjiang 832003, China; College of Life Sciences, Shihezi University, Shihezi, Xinjiang 832003, China.
College of Animal Science and Technology, Shihezi University, Shihezi, Xinjiang 832003, China.
Biomed Pharmacother. 2025 Jun;187:118077. doi: 10.1016/j.biopha.2025.118077. Epub 2025 Apr 24.
Brucellosis is a zoonotic disease that poses a significant threat to both animal husbandry and public health. Currently available vaccines for brucellosis are all live attenuated forms, which carry the risk of potential infectivity and provide a relatively limited range of protection. In contrast, inactivated vaccines are perceived to exhibit poor protective efficacy and fail to elicit effective cellular immunity. This study aimed to comprehensively evaluate the efficacy of the Brucella inactivated vaccine (CF) with the objective of developing a safer and more effective candidate for brucellosis vaccination.
Firstly, we evaluated the safety of CF in mice. Subsequently, we immunized mice with CF using various doses and methods, determining the optimal immunization dose and method through challenge testing. We evaluated the vaccine's immunogenicity by detecting the cellular and humoral immune levels induced by CF in mice, and assessed the vaccine's protective effect based on the post challenge organ bacterial load. Additionally, we evaluated the protective effects of dual doses and secondary immunization in guinea pigs.
The results indicate that CF is safe and non-toxic; it induced significant increases in specific IgG antibody levels against Brucella during the early stages and markedly enhanced the T cell immune response, thereby promoting a Th1-biased immune response in mice. Following the challenge, CF demonstrated protective efficacy comparable to that of the S2 vaccine against B. melitensis biovar 3 infection in mice. CF-immunized guinea pigs were able to resist infection by B. melitensis M28 and B. melitensis biovar 3.
In summary, CF significantly induces both humoral and cellular immunity in mice. This study reports for the first time that a safe and effective inactivated Brucella vaccine (CF) can induce cellular immune responses and effectively prevent animal brucellosis.
布鲁氏菌病是一种人畜共患病，对畜牧业和公共卫生构成重大威胁。目前可用的布鲁氏菌病疫苗均为减毒活疫苗，存在潜在感染风险，且保护范围相对有限。相比之下，灭活疫苗被认为保护效果不佳，无法引发有效的细胞免疫。本研究旨在全面评估布鲁氏菌灭活疫苗（CF）的效果，以期开发出一种更安全、有效的布鲁氏菌病疫苗候选产品。
首先，我们评估了CF在小鼠中的安全性。随后，我们用不同剂量和方法给小鼠接种CF，通过攻毒试验确定最佳免疫剂量和方法。我们通过检测CF在小鼠中诱导的细胞免疫和体液免疫水平来评估疫苗的免疫原性，并根据攻毒后器官中的细菌载量评估疫苗的保护效果。此外，我们还评估了双剂量和二次免疫在豚鼠中的保护作用。
结果表明CF安全无毒；它在早期显著提高了针对布鲁氏菌的特异性IgG抗体水平，并显著增强了T细胞免疫反应，从而在小鼠中促进了以Th1为主的免疫反应。攻毒后，CF在小鼠中对羊种布鲁氏菌生物变种3感染表现出与S2疫苗相当的保护效果。接种CF的豚鼠能够抵抗羊种布鲁氏菌M28和羊种布鲁氏菌生物变种3的感染。
综上所述，CF在小鼠中显著诱导了体液免疫和细胞免疫。本研究首次报道了一种安全有效的布鲁氏菌灭活疫苗（CF）可诱导细胞免疫反应并有效预防动物布鲁氏菌病。
