D'iakov I N, Pokrovskiĭ V S, Sannikova E P, Bulushova N V, Pokrovskaia M V, Aleksandrova S S
Zh Mikrobiol Epidemiol Immunobiol. 2014 Nov-Dec(6):100-4.
Evaluate immune response in mice against various L-asparaginases and determine their cross-immunogenicity.
The studies were carried out in C57Bl(6j) line mice. Immunogenicity of L-asparaginases was studied: Escherichia coli type II (recombinant) (Medak, Germany) (EcA); Erwinia carotovora type II (ErA); Yersinia pseudotuberculosis type II (YpA); Rhodospirillum rubrum type I (RrA); Wollinella succinogenes type II (WsA). Immune response against the administered antigens was determined in EIA.
Y. pseudotuberculosis L-asparaginase was the most immunogenic, E. coli--the least immunogenic. E. carotovora, R. rubrum, W. succinogenes asparaginases displayed intermediate immunogenicity. The results of cross-immunogenicity evaluation have established, that blood sera of mice, that had received YpA, showed cross-immunogenicity against all the other L-asparaginase preparations except E. carotovora. During immunization with E. coli L-asparaginase the developed antibodies also bound preparation from E. carotovora. Sera from mice immunized with W. succinogenes, E. carotovora and R. rubrum L-asparaginases had cross-reaction only with EcA and did not react with other preparations.
Cross-immunogenicity of the studied L-asparaginases was determined. A sequence of administration of the studied preparation is proposed that allows to minimize L-asparaginase neutralization by cross-reacting antibodies.
评估小鼠对各种L-天冬酰胺酶的免疫反应,并确定它们的交叉免疫原性。
研究在C57Bl(6j)品系小鼠中进行。研究了L-天冬酰胺酶的免疫原性:II型大肠杆菌(重组)(德国梅达克)(EcA);胡萝卜软腐欧文氏菌II型(ErA);假结核耶尔森氏菌II型(YpA);深红红螺菌I型(RrA);产琥珀酸沃林氏菌II型(WsA)。通过酶免疫测定法确定对所给予抗原的免疫反应。
假结核耶尔森氏菌L-天冬酰胺酶免疫原性最强,大肠杆菌L-天冬酰胺酶免疫原性最弱。胡萝卜软腐欧文氏菌、深红红螺菌、产琥珀酸沃林氏菌的天冬酰胺酶表现出中等免疫原性。交叉免疫原性评估结果表明,接受YpA的小鼠血清对除胡萝卜软腐欧文氏菌外的所有其他L-天冬酰胺酶制剂均表现出交叉免疫原性。在用大肠杆菌L-天冬酰胺酶免疫期间,产生的抗体也与胡萝卜软腐欧文氏菌的制剂结合。用产琥珀酸沃林氏菌、胡萝卜软腐欧文氏菌和深红红螺菌L-天冬酰胺酶免疫的小鼠血清仅与EcA有交叉反应,与其他制剂无反应。
确定了所研究L-天冬酰胺酶的交叉免疫原性。提出了所研究制剂的给药顺序,以尽量减少交叉反应抗体对L-天冬酰胺酶的中和作用。