Farjah Ali, Owlia Parviz, Siadat Seyed Davar, Mousavi Seyed Fazlollah, Ardestani Mehdi Shafiee, Mohammadpour Hashem Khorsand
Department of Biology, Shahed University, Tehran, Iran; Department of Microbiology, Microbial research center, Pasteur Institute of Iran, Tehran, Iran.
APMIS. 2015 Feb;123(2):175-83. doi: 10.1111/apm.12337. Epub 2014 Dec 3.
Pseudomonas aeruginosa is an opportunistic pathogen that causes serious infections, is usually resistant to antimicrobial agents, and is the leading cause of morbidity and premature mortality in patients with cystic fibrosis (CF). Mucoid strains of P. aeruginosa produce a virulence factor known as alginate. Developing a strategy to raise opsonic antibodies against alginate could be promising for the treatment of P. aeruginosa infection in CF patients. Conjugation of alginate to a carrier protein is a good method for increasing the immunogenicity of alginate. We conjugated alginate to the outer membrane vesicle (OMV) of Neisseria meningitidis serogroup B, which is a safe carrier protein, and evaluated its efficacy in mice. To evaluate the immune response, total IgG, IgG1, IgG2a, and IgG2b titers were analyzed. Immunization of mice with the alginate-OMV conjugate raised the levels of opsonic antibodies, and the vaccinated mice were protected when challenged intranasally with P. aeruginosa. Further studies showed that the conjugated vaccine could eliminate P. aeruginosa from the lungs of infected mice. This study supports the proposal that immunization of mice with an alginate-OMV conjugate vaccine could be safe and protective against P. aeruginosa infection.
铜绿假单胞菌是一种机会致病菌,可引发严重感染,通常对抗菌药物具有耐药性,并且是囊性纤维化(CF)患者发病和过早死亡的主要原因。铜绿假单胞菌的黏液型菌株会产生一种名为藻酸盐的毒力因子。制定一种策略来提高针对藻酸盐的调理素抗体水平,对于治疗CF患者的铜绿假单胞菌感染可能具有前景。将藻酸盐与载体蛋白偶联是提高藻酸盐免疫原性的一种好方法。我们将藻酸盐与B群脑膜炎奈瑟菌的外膜囊泡(OMV)偶联,B群脑膜炎奈瑟菌的外膜囊泡是一种安全的载体蛋白,并在小鼠中评估了其效果。为了评估免疫反应,分析了总IgG、IgG1、IgG2a和IgG2b滴度。用藻酸盐-OMV偶联物免疫小鼠提高了调理素抗体水平,并且在用铜绿假单胞菌进行鼻内攻击时,接种疫苗的小鼠受到了保护。进一步的研究表明,偶联疫苗可以清除感染小鼠肺部的铜绿假单胞菌。这项研究支持了用藻酸盐-OMV偶联疫苗免疫小鼠可能安全且能预防铜绿假单胞菌感染的提议。