Attenuated nontoxinogenic and nonencapsulated recombinant Bacillus anthracis spore vaccines protect against anthrax
Attenuated nontoxinogenic and nonencapsulated recombinant Bacillus anthracis spore vaccines protect against anthrax
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DOI：
10.1128/iai.68.8.4549-4558.2000
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发表时间：
2000-08-01
影响因子：
3.1
通讯作者：
Shafferman, A
中科院分区：
文献类型：
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作者：
Cohen, S;Mendelson, I;Shafferman, A
构建了几种不同重组保护性抗原(RPA)表达水平的高度减毒、无毒和非囊化炭疽芽孢杆菌疫苗。生化分析(包括电喷雾质谱分析和N末端氨基酸测序)以及生物学和免疫学试验表明，RPA保留了天然PA的特征。用其中一株重组菌株MASC-10的5×10(7)孢子单次免疫豚鼠，诱导产生高滴度的中和抗PA抗体。这种免疫反应是持久的(至少12个月)，并提供了对致命的(卷)炭疽孢子的攻击的保护。重组炭疽芽胞疫苗似乎比营养细胞疫苗更有效。此外，虽然结果清楚地表明PA的表达水平与疫苗的效力之间存在直接关联，但它们也表明一些炭疽芽胞相关抗原(S)可能在保护性免疫中起到了重要作用。
Several highly attenuated spore-forming nontoxinogenic and nonencapsulated Bacillus anthracis vaccines differing in levels of expression of recombinant protective antigen (rPA) were constructed. Biochemical analyses (including electrospray mass spectroscopy and N terminus amino acid sequencing) as well as biological and immunological tests demonstrated that the rPA retains the characteristics of native PA. A single immunization of guinea pigs with 5 x 10(7) spores of one of these recombinant strains, MASC-10, expressing high levels of rPA (greater than or equal to 100 mu g/ml) from a constitutive heterologous promoter induced high titers of neutralizing anti-PA antibodies. This immune response was long lasting (at least 12 months) and provided protection against a lethal challenge of virulent (Vollum) anthrax spores. The recombinant B. anthracis spore vaccine appears to be more efficacious than the vegetative cell vaccine. Furthermore, while results clearly suggest a direct correlation between the level of expression of PA and the potency of the vaccine, they also suggest that some B. anthracis spore-associated antigen(s) may contribute in a significant manner to protective immunity.