Complete, long-lasting protection against malaria of mice primed and boosted with two distinct viral vectors expressing the same plasmodial antigen
Complete, long-lasting protection against malaria of mice primed and boosted with two distinct viral vectors expressing the same plasmodial antigen
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DOI：
10.1073/pnas.191380898
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发表时间：
2001-09-25
影响因子：
11.1
通讯作者：
Nussenzweig, RS
中科院分区：
文献类型：
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作者：
Bruña-Romera, O;González-Aseguinolaza, G;Nussenzweig, RS
我们报告说，完全保护免受疟疾和总抑制肝脏阶段的发展和寄生虫血症，获得100%的BALB/c小鼠与复制缺陷型重组腺病毒表达的约氏疟原虫环子孢子（CS）蛋白（AdPyCS），然后用减毒重组牛痘病毒，表达相同的疟疾抗原，VacPyCS的助推器。我们发现，当用这两种病毒载体引发和加强之间的时间从2周延长到8周或更长时间时，这些小鼠中活化的CS特异性CD8+和CD4 + T细胞的水平增加，抗子孢子抗体滴度更高，保护作用更强。最重要的是，通过使用该免疫方案，发现免疫小鼠的保护是持久的，即在引发后3个半月所有动物对感染具有完全抗性。这些结果表明，用AdPyCS免疫产生高效的记忆T和B细胞，其可以在用VacPyCS加强引发后很长时间被召回。
We report that complete protection against malaria and total inhibition of liver stage development and parasitemia was obtained in 100% of BALB/c mice primed with a replication-defective recombinant adenovirus expressing the circumsporozoite (CS) protein of Plasmodium yoelii (AdPyCS), followed by a booster with an attenuated recombinant vaccinia virus, expressing the same malaria antigen, VacPyCS. We found increased levels of activated CS-specific CD8+ and CD4+ T cells, higher anti-sporozoite antibody titers, and greater protection in these mice, when the time between priming and boosting with these two viral vectors was extended from 2 to 8 or more weeks. Most importantly, by using this immunization regimen, the protection of the immunized mice was found to be long-lasting, namely complete resistance to infection of all animals 3 1/2 months after priming. These results indicate that immunization with AdPyCS generates highly effective memory T and B cells that can be recalled long after priming by boosting with VacPyCS.