Improved immunogenicity and efficacy of the recombinant 19-kilodalton merozoite surface protein 1 by the addition of oligodeoxynucleotide and aluminum hydroxide gel in a murine malaria vaccine model
Improved immunogenicity and efficacy of the recombinant 19-kilodalton merozoite surface protein 1 by the addition of oligodeoxynucleotide and aluminum hydroxide gel in a murine malaria vaccine model
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DOI：
10.1128/iai.70.2.692-701.2002
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发表时间：
2002-02-01
影响因子：
3.1
通讯作者：
Kaslow, DC
中科院分区：
文献类型：
--
作者：
Near, KA;Stowers, AW;Kaslow, DC
用酵母分泌的约氏疟原虫衍生的19千道尔顿裂殖子表面蛋白I（yMSP 1（19））对小鼠进行疫苗接种已显示出对约氏疟原虫致死菌株的攻击提供保护。当MSPI在弗氏佐剂中乳化时可以实现无菌免疫，但当其吸附到氢氧化铝凝胶（明矾）时则不能。因为完全弗氏佐剂不是用于人类的可接受的佐剂，所以必须鉴定替代佐剂以配制MSPI 19作为用于人类的疫苗。为了确定具有CpG基序的寡脱氧核苷酸（ODN）（据报道是一种强大的新型佐剂）是否可以增强yMSP 1的免疫原性（19），C57 BL/6小鼠用与弗氏佐剂、明矾或ODN加明矾配制的yMSP 1（19）接种，并用约氏疟原虫17 XL无性血液期寄生虫静脉内攻击。通过调节缓冲液（磷酸盐对乙酸盐）和pH来优化免疫原和佐剂对明矾的吸附。我们发现，腹膜内（i. p.）注射的ODN加明矾与yMSP 1（19）的佐剂组合，免疫球蛋白G（IgG）yMSP 1（19）特异性抗体产生增加12倍于腹膜内给予弗氏佐剂，3-倍于皮下（s.c.）给予的弗氏佐剂，300-腹膜内注射明矾，和48倍于明矾皮下给药。接受alum-ODN-yMSP 1的组中的主要抗体同种型是IgG 1（19）。抗体水平的增加与约氏疟原虫17 XL攻击的保护相关。在alum-ODN-yMSP 1（19）组中，yMSP 1（19）刺激的脾细胞中γ干扰素的上清液细胞因子水平显著升高。白细胞介素-10（IL-10）水平也升高;然而，未检测到IL-5。细胞因子谱以及主要的IgG 1抗体同种型表明保护性免疫应答是混合的Th 1/Th 2应答。
Vaccination of mice with yeast-secreted Plasmodium yoelii-derived 19-kilodalton merozoite surface protein I (yMSP1(19)) has been shown to afford protection from challenge with a lethal strain of A yoelii. Sterile immunity can be achieved when MSPI, is emulsified in Freund adjuvant but not when it is adsorbed to aluminum hydroxide gel (alum). Because complete Freund adjuvant is not an acceptable adjuvant for use in humans, alternative adjuvants must be identified for formulating MSPI 19 as a vaccine for use in humans. To determine whether oligodeoxynucleotides with CpG motifs (ODN), reported to be a powerful new class of adjuvants, could enhance the immunogenicity of yMSP1(19), C57BL/6 mice were vaccinated either with yMSP1(19) formulated with Freund adjuvant, with alum, or with ODN plus alum and challenged intravenously with A yoelii 17XL asexual blood-stage parasites. Adsorption of immunogen and adjuvant to alum was optimized by adjusting buffer (phosphate versus acetate) and pH. We found that the adjuvant combination of ODN plus alum with yMSP1(19) injected intraperitoneally (i.p.), increased immunoglobulin G (IgG) yMSP1(19)-specific antibody production 12-fold over Freund adjuvant given i.p., 3-fold over Freund adjuvant given subcutaneously (s.c.), 300-fold over alum given i.p., and 48-fold over alum given s.c. The predominant antibody isotype in the group receiving alum-ODN-yMSP1(19) was IgG1. Increased antibody levels correlated to protection from a challenge with A yoelii 17XL. Supernatant cytokine levels of gamma interferon in yMSP1(19)-stimulated splenocytes were dramatically elevated in the alum-ODN-yMSP1(19) group. Interleukin-10 (IL-10) levels were also elevated; however, no IL-5 was detected. The cytokine profile, as well as the predominant IgG1 antibody isotype, suggests the protective immune response was a mixed Th1/Th2 response.