Immunization against a merozoite sheddase promotes multiple invasion of red blood cells and attenuates Plasmodium infection in mice.
Immunization against a merozoite sheddase promotes multiple invasion of red blood cells and attenuates Plasmodium infection in mice.
复制标题
DOI：
10.1186/1475-2875-13-313
复制
发表时间：
2014-08-12
期刊：
影响因子：
3
通讯作者：
Bosch J
中科院分区：
文献类型：
--
作者：
Smith RC;Colón-López DD;Bosch J
枯草杆菌样蛋白酶2 （SUB2）是一种保守的丝氨酸蛋白酶，被疟原虫利用作为成功入侵宿主红细胞所需的表面脱落酶，并与蚊子中肠卵母细胞入侵有关。为了确定SUB2是否是干扰疟原虫发育的合适疫苗靶点，在其脊椎动物和无脊椎动物宿主中检测了SUB2免疫对疟原虫生命周期的影响。用与Keyhole帽贝血青素（KLH）结合的SUB2肽或单独的KLH免疫瑞士韦氏小鼠，然后用伯氏疟原虫攻毒。为确定免疫对寄生虫发育的影响，采用血膜和吉姆萨染色评价感染小鼠。此外，收集的免疫血清用于未免疫的伯氏疟原虫感染小鼠进行被动免疫实验，以确定SUB2在蚊子体内寄生虫发育中的潜在作用。在伯氏假单胞菌攻击后，与对照组免疫小鼠相比，经sub2免疫的小鼠出现较低的寄生虫血症，并显示出更高的存活率。此外，SUB2免疫可导致多次入侵的红细胞数量增加，这表明SUB2抗体干扰了裂殖子的入侵。被动免疫实验表明，SUB2可能在卵母细胞侵袭中没有主要作用，但这需要进一步研究。通过干扰红细胞入侵，针对SUB2的免疫限制了疟疾寄生虫的发展，并提供了对严重疟疾的保护。总之，这些结果为未来研究在更相关的人类疟疾模型中使用SUB2作为阻断寄生虫发育的疫苗或药物靶点提供了原理证明证据。本文的在线版本（doi:10.1186/1475-2875-13-313）包含补充材料，可供授权用户使用。
Subtilisin-like protease 2 (SUB2) is a conserved serine protease utilized by Plasmodium parasites as a surface sheddase required for successful merozoite invasion of host red blood cells and has been implicated in ookinete invasion of the mosquito midgut. To determine if SUB2 is a suitable vaccine target to interfere with malaria parasite development, the effects of SUB2-immunization on the Plasmodium life cycle were examined in its vertebrate and invertebrate hosts. Swiss Webster mice were immunized with SUB2 peptides conjugated to Keyhole limpet hemocyanin (KLH) or KLH alone, and then challenged with Plasmodium berghei. To determine the effects of immunization on parasite development, infected mice were evaluated by blood film and Giemsa staining. In addition, collected immune sera were used to perform passive immunization experiments in non-immunized, P. berghei-infected mice to determine the potential role of SUB2 in parasite development in the mosquito. Following P. berghei challenge, SUB2-immunized mice develop a lower parasitaemia and show improved survival when compared to control immunized mice. Moreover, SUB2 immunization results in an increase in the number of multiply invaded red blood cells, suggesting that SUB2 antibodies interfere with merozoite invasion. Passive immunization experiments imply that SUB2 may not have a major role in ookinete invasion, but this requires further investigation. By interfering with red blood cell invasion, immunization against SUB2 limits malaria parasite development and confers protection from severe malaria. Together, these results provide proof-of-principle evidence for future investigation into the use of SUB2 as a vaccine or drug target to interrupt parasite development in more relevant human malaria models. The online version of this article (doi:10.1186/1475-2875-13-313) contains supplementary material, which is available to authorized users.
登录
查看更多内容
影响因子：
15.8
作者：
Delves M;Plouffe D;Scheurer C;Meister S;Wittlin S;Winzeler EA;Sinden RE;Leroy D
通讯作者：
Leroy D
影响因子：
4.7
作者：
Graewe, Stefanie;Retzlaff, Silke;Heussler, Volker T.
通讯作者：
Heussler, Volker T.
影响因子：
6.7
作者：
Harris PK;Yeoh S;Dluzewski AR;O'Donnell RA;Withers-Martinez C;Hackett F;Bannister LH;Mitchell GH;Blackman MJ
通讯作者：
Blackman MJ
影响因子：
2.2
作者：
Ramasamy, R;Yasawardena, S;Ramasamy, MS
通讯作者：
Ramasamy, MS
影响因子：
2.7
作者：
Boucher, Lauren E.;Bosch, Juergen
通讯作者：
Bosch, Juergen