Abstract：
Due to its antimicrobial resistance characteristics, the World Health Organization (WHO) classifies A. baumannii as one of the critical priority pathogens for the development of new therapeutic strategies. Vaccination has been approached as an interesting strategy to overcome the lack of effective antimicrobials and the long time required to develop and approve new drugs. In this study, we aimed to evaluate as a vaccine the hypothetical adhesin protein CAM87009.1 in its recombinant format (rCAM87009.1) associated with aluminum hydroxide (Alhydrogel®) or biogenic silver nanoparticles (bio-AgNP) as adjuvant components against lethal infection by A. baumannii MDR strain. Both vaccine formulations were administered in three doses intramuscularly in BALB/c murine models and the vaccinated animals were tested in a challenge assay with A. baumannii MDR strain (DL100). rCAM87009.1 protein associated with both adjuvants was able to protect 100 % of animals challenged with the lethal strain during the challenge period. After the euthanasia of the animals, no A. baumannii colonies were detected in the lungs of animals vaccinated with the rCAM87009.1 protein in both formulations. Since the first immunization, high IgG antibody titers were observed (1:819,200), with results being statistically similar in both vaccine formulations evaluated. rCAM87009.1 associated with both adjuvants was capable of inducing at least one class of isotypes associated with the processes of neutralization (IgG2b and IgA for bio-AgNP and Alhydrogel®, respectively), opsonization (IgG1 in both vaccines) and complement activation (IgM and IgG3 for bio-AgNP and Alhydrogel®, respectively). Furthermore, reduced tissue damage was observed in animals vaccinated with rCAM87009.1 + bio-AgNP when compared to animals vaccinated with Alhydrogel®. Our results indicate that the rCAM87009.1 protein associated with both bio-AgNP and Alhydrogel® are combinations capable of promoting immunity against infections caused by A. baumannii MDR. Additionally, we demonstrate the potential of silver nanoparticles as alternative adjuvant molecules to the use of aluminum salts.
摘要：
由于其耐药性特点,世界卫生组织（WHO）将鲍曼不动杆菌列为开发新治疗策略的关键优先病原体之一。疫苗接种已被视为一种有趣的策略，以克服缺乏有效的抗微生物剂以及开发和批准新药所需的长时间。在这项研究中,我们的目的是评估假设性粘附素蛋白CAM87009.1的重组形式(rCAM87009.1)与氢氧化铝(Alhydrogel®)或生物银纳米颗粒(bio-AgNP)结合作为佐剂成分的疫苗,以对抗鲍曼不动杆菌MDR株的致死性感染.两种疫苗制剂在BALB/c鼠模型中以三个剂量肌内施用,并且在用鲍曼不动杆菌MDR菌株(DL100)的攻击测定中测试接种的动物。与两种佐剂相关的rCAM87009.1蛋白能够在攻击期间保护100%的被致死菌株攻击的动物。动物安乐死后，在两种制剂中,在用rCAM87009.1蛋白接种的动物的肺中均未检测到鲍曼不动杆菌菌落。自从第一次免疫以来，观察到高IgG抗体滴度（1：819,200），评估的两种疫苗制剂的结果在统计学上相似。与两种佐剂相关的rCAM87009.1能够诱导至少一类与中和过程相关的同种型（用于bio-AgNP和Alhydrogel®的IgG2b和IgA，分别)，调理作用（两种疫苗中的IgG1）和补体激活（用于bio-AgNP和Alhydrogel®的IgM和IgG3，分别)。此外，与用Alhydrogel®接种的动物相比,在用rCAM87009.1+bio-AgNP接种的动物中观察到减少的组织损伤。我们的结果表明，与bio-AgNP和Alhydrogel®相关的rCAM87009.1蛋白是能够促进针对鲍曼不动杆菌MDR引起的感染的免疫力的组合。此外,我们证明了银纳米颗粒作为使用铝盐的替代佐剂分子的潜力。
