Immune responses induced by gene gun or intramuscular injection of DNA vaccines that express immunogenic regions of the serine repeat antigen from Plasmodium falciparum

Immune responses induced by gene gun or intramuscular injection of DNA vaccines that express immunogenic regions of the serine repeat antigen from Plasmodium falciparum
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DOI:
10.1128/iai.67.10.5163-5169.1999
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发表时间:
1999-10-01
影响因子:
3.1
通讯作者:
Bzik, DJ
Bzik, DJ
中科院分区:
医学2区
文献类型:
--
作者:
Belperron, AA;Feltquate, D;Bzik, DJ

文献摘要

被引文献

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恶性疟原虫的肝脏和血液阶段表达的丝氨酸重复抗原(SERA)是人类疟疾疫苗的候选蛋白。我们比较了肌内注射和皮内注射表达sera的质粒DNA疫苗对小鼠的免疫反应。用编码SERA整个47-kDa结构域(氨基酸17 ~ 382)或n端结构域(氨基酸17 ~ 110)的pcdna3质粒免疫小鼠。在DNA接种SERA的n端结构域后,检测到最小的抗体反应,这表明通过这种疫苗递送途径,仅n端结构域不是高度免疫原性的。用基因枪传递47-kDa结构域的小鼠免疫后,小鼠对抗原的血清抗体滴度明显高于用i;m免疫的小鼠。注射同样的质粒可以。用血清质粒DNA进行免疫后,对血清蛋白产生的抗体的主要亚型是免疫球蛋白G1。血清DNA质粒与表达乙型肝炎表面抗原(pCMV-s)的质粒经i.m.途径共同免疫小鼠,其抗血清效价高于单独免疫小鼠的血清DNA质粒。DNA疫苗接种可提供一种可行的替代方案,或可与基于蛋白质的亚单位疫苗结合使用,以最大限度地提高包括血清蛋白免疫原区在内的人疟疾疫苗的效力。
The liver- and blood-stage-expressed serine repeat antigen (SERA) of Plasmodium falciparum is a candidate protein for a human malaria vaccine. We compared the immune responses induced in mice immunized with SERA-expressing plasmid DNA vaccines delivered by intramuscular (i.m.) injection or delivered intradermally by Gene Gun immunization. Mice were immunized with a pcdna3 plasmid encoding the entire 47-kDa domain of SERA (amino acids 17 to 382) or the N-terminal domain (amino acids 17 to 110) of SERA. Minimal antibody responses were detected following DNA vaccination with the N-terminal domain of SERA, suggesting that the N-terminal domain alone is not highly immunogenic by this route of vaccine delivery. Immunization of mice by Gene Gun delivery of the 47-kDa domain of SERA elicited a significantly higher serum antibody titer to the antigen than immunization of mice by i;m. injection with the same plasmid did. The predominant isotype subclass of the antibodies elicited to the SERA protein following i.m. and Gene Gun immunizations with SERA plasmid DNA was immunoglobulin G1. Coimmunization of mice with SERA plasmid DNA and a plasmid expressing the hepatitis B surface antigen (pCMV-s) by the i.m. route resulted in higher anti-SERA titers than those generated in mice immunized with the SERA DNA plasmid alone. Vaccination,vith DNA may provide a viable alternative or may be used in conjunction,vith protein-based subunit vaccines to maximize the efficacy of a human malaria vaccine that includes immunogenic regions of the SERA protein.