Retamal-Díaz Angello, Riquelme-Neira Roberto, Sáez Darwin, Rivera Alejandra, Fernández Pablo, Cabrera Alex, Guzmán Carlos A, Oñate Angel
Molecular Immunology Laboratory, Department of Microbiology, Faculty of Biological Sciences, Universidad de Concepción, Concepción, Chile.
Department of Vaccinology and Applied Microbiology, Helmholtz Centre for Infection Research, Braunschweig, Germany.
Clin Vaccine Immunol. 2014 Nov;21(11):1474-80. doi: 10.1128/CVI.00554-14. Epub 2014 Aug 27.
This study was conducted to evaluate the immunogenicity and protective efficacy of a DNA vaccine encoding Brucella abortus Cu,Zn superoxide dismutase (SOD) using the Toll-like receptor 2/6 agonist S-[2,3-bispalmitoyiloxy-(2R)-propyl]-R-cysteinyl-amido-monomethoxy polyethylene glycol (BPPcysMPEG) as an adjuvant. Intranasal coadministration of BPPcysMPEG with a plasmid carrying the SOD-encoding gene (pcDNA-SOD) into BALB/c mice elicited antigen-specific humoral and cellular immune responses. Humoral responses were characterized by the stimulation of IgG2a and IgG1 and by the presence of SOD-specific secretory IgA in nasal and bronchoalveolar lavage fluids. Furthermore, T-cell proliferative responses and increased production of gamma interferon were also observed upon splenocyte restimulation with recombinant SOD. Cytotoxic responses were also stimulated, as demonstrated by the lysis of RB51-SOD-infected J774.A1 macrophages by cells recovered from immunized mice. The pcDNA-SOD/BPPcysMPEG formulation induced improved protection against challenge with the virulent strain B. abortus 2308 in BALB/c mice over that provided by pcDNA-SOD, suggesting the potential of this vaccination strategy against Brucella infection.
本研究旨在评估以Toll样受体2/6激动剂S-[2,3-双棕榈酰氧基-(2R)-丙基]-R-半胱氨酰-氨基-单甲氧基聚乙二醇(BPPcysMPEG)作为佐剂的编码流产布鲁氏菌铜锌超氧化物歧化酶(SOD)的DNA疫苗的免疫原性和保护效力。将BPPcysMPEG与携带SOD编码基因的质粒(pcDNA-SOD)经鼻共同给予BALB/c小鼠,可引发抗原特异性体液免疫和细胞免疫反应。体液免疫反应的特征为IgG2a和IgG1受到刺激,以及在鼻腔和支气管肺泡灌洗液中存在SOD特异性分泌型IgA。此外,在用重组SOD再次刺激脾细胞时,还观察到T细胞增殖反应以及γ干扰素产生增加。细胞毒性反应也受到刺激,这可通过免疫小鼠回收的细胞对RB51-SOD感染的J774.A1巨噬细胞的裂解来证明。与pcDNA-SOD相比,pcDNA-SOD/BPPcysMPEG制剂在BALB/c小鼠中对强毒株流产布鲁氏菌2308攻击的保护作用有所改善,表明这种疫苗接种策略针对布鲁氏菌感染具有潜力。