Wunderlich G, Moura I C, del Portillo H A
Instituto Ciências Biomédicas 2, Universidade de São Paulo, São Paulo SP, CEP 05508-900, Brazil.
Infect Immun. 2000 Oct;68(10):5839-45. doi: 10.1128/IAI.68.10.5839-5845.2000.
The genetic immunization of rodents with a plasmid coding for a Plasmodium chabaudi merozoite surface protein 1 (C terminus)-hepatitis B virus surface fusion protein (pPcMSP1(19)-HBs) provided protection of mice against subsequent lethal challenge with P. chabaudi chabaudi PC1-infected red blood cells. The percentage of survivor mice was higher in DNA-immunized mice than in animals immunized with a recombinant rPcMSP1(19)- glutathione S-transferase fusion protein administered in Freund adjuvant. In all mice immunized with the pPcMSP1(19)-HBs, a Th1-specific response, including the production of anti-MSP1(19)-specific immunoglobulins predominantly of the immunoglobulin G2a subtype and reacting almost exclusively against discontinuous epitopes, was elicited. The coinjection of Th1-type cytokine-expressing plasmids (gamma interferon, interleukin-2, and granulocyte-macrophage colony-stimulating factor) mostly abolished protection and boosting of MSP1(19)-specific antibodies. The inclusion of a lymph node-targeting signal did not significantly increase protection. These data provide further evidence that MSP1(19)-HBs DNA constructs might be useful as components of a genetic vaccine against the asexual blood stages of Plasmodium.
用编码恰氏疟原虫裂殖子表面蛋白1(C末端)-乙型肝炎病毒表面融合蛋白(pPcMSP1(19)-HBs)的质粒对啮齿动物进行基因免疫,可保护小鼠免受随后恰氏疟原虫PC1感染的红细胞的致死性攻击。DNA免疫的小鼠中存活小鼠的百分比高于用弗氏佐剂中给予的重组rPcMSP1(19)-谷胱甘肽S-转移酶融合蛋白免疫的动物。在用pPcMSP1(19)-HBs免疫的所有小鼠中,引发了Th1特异性反应,包括产生主要为免疫球蛋白G2a亚型且几乎仅针对不连续表位的抗MSP1(19)特异性免疫球蛋白。共注射表达Th1型细胞因子的质粒(γ干扰素、白细胞介素-2和粒细胞-巨噬细胞集落刺激因子)大多消除了对MSP1(19)特异性抗体的保护和增强作用。包含淋巴结靶向信号并未显著增加保护作用。这些数据提供了进一步的证据,表明MSP1(19)-HBs DNA构建体可能作为抗疟原虫无性血液阶段基因疫苗的组成部分有用。