Immunization of mice with DNA-based Pfs25 elicits potent malaria transmission-blocking antibodies.
Immunization of mice with DNA-based Pfs25 elicits potent malaria transmission-blocking antibodies.
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用基于 DNA 的 Pfs25 免疫小鼠会引发有效的疟疾传播阻断抗体。
DOI：
10.1128/iai.67.4.1688-1693.1999
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发表时间：
1999
影响因子：
3.1
通讯作者：
Kumar,N
中科院分区：
文献类型：
--
作者：
Lobo,CA;Dhar,R;Kumar,N
除了病媒控制和疟疾化疗外，还需要免疫干预，以阻止疟疾的死灰复燃，这种疾病每年对3亿至5亿人的健康造成毁灭性影响。我们已经采取了一种疫苗接种策略，该策略基于用编码恶性疟原虫性阶段Pfs 25和Pfg 27的两种抗原的基因在小鼠中进行DNA免疫，以诱导生物学上重要的抗体，该抗体可以阻断疟原虫在按蚊中的发育，从而阻断疾病的传播。编码Pfs 25的DNA通过肌肉注射途径给药时，无论是单独还是与编码Pfg 27的DNA一起给药，都具有最有效的传播阻断作用，导致蚊子中肠中卵囊数量减少97%，感染率降低75%。用编码Pfg 27-Pfs 25融合蛋白的DNA免疫效果较差，编码Pfg 27的DNA在血清中引起的抗体对寄生虫的感染性只有适度的影响。这些结果首次表明，DNA疫苗接种可以导致在小鼠中产生有效的传播阻断抗体，并建议Pfs 25基因应包括作为多组分DNA疫苗的一部分。
Immunological intervention, in addition to vector control and malaria chemotherapy, will be needed to stop the resurgence of malaria, a disease with a devastating impact on the health of 300 to 500 million people annually. We have pursued a vaccination strategy, based on DNA immunization in mice with genes encoding two antigens present on the sexual stages ofPlasmodium falciparum, Pfs25 and Pfg27, to induce biologically important antibodies that can block development of the parasite in theAnophelesmosquito and thus transmission of the disease. DNA encoding Pfs25 when administered by the intramuscular route, either alone or with DNA encoding Pfg27, had the most potent transmission-blocking effects, resulting in up to a 97% decrease in oocyst numbers in mosquito midguts and a 75% decrease in rate of infection. Immunization with DNA encoding a Pfg27-Pfs25 fusion protein was less effective and DNA encoding Pfg27 elicited antibodies in sera that had only modest effects on the infectivity of the parasite. These results show for the first time that DNA vaccination can result in potent transmission-blocking antibodies in mice and suggest that the Pfs25 gene should be included as part of a multicomponent DNA vaccine.