Japanese encephalitis DNA vaccine candidates expressing premembrane and envelope genes induce virus-specific memory B cells and long-lasting antibodies in swine
Japanese encephalitis DNA vaccine candidates expressing premembrane and envelope genes induce virus-specific memory B cells and long-lasting antibodies in swine
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DOI：
10.1006/viro.1999.0142
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发表时间：
2000-03-01
期刊：
影响因子：
3.7
通讯作者：
Mason, PW
中科院分区：
文献类型：
--
作者：
Konishi, E;Yamaoka, M;Mason, PW
猪是乙型脑炎病毒在准家庭环境中的重要传播者。在这项研究中，评价了两种乙脑DNA疫苗候选物在猪中的免疫原性。两种疫苗质粒编码由JE病毒的前膜信号（prM）、prM和包膜（E）编码区组成的盒。一种质粒命名为pcJEME，基于商业载体（pcDNA 3），而另一种质粒命名为pNJEME，基于设计用于解决DNA疫苗使用的一些安全性问题的载体（pNGVL 4a）。这两种质粒在小鼠或猪中的免疫原性无差异。以100至450 μ g剂量间隔3周用DNA疫苗免疫的猪在第二次免疫后1周产生1：40至1：160的中和和血凝抑制（HAI）抗体滴度。然而，给予两剂商业乙脑疫苗（福尔马林灭活病毒制剂; JEVAX-A）的猪在加强免疫后产生了低（1：10）或不可检测的抗体应答。有趣的是，DNA疫苗在猪中引起的血清抗体滴度高于在小鼠中检测到的那些。在用病毒抗原（JEVAX-A）加强以检测回忆应答后8天，用DNA疫苗免疫两次的猪显示HAI滴度升高>100倍，表明抗体应答的强烈回忆。在用UNA疫苗免疫两次后，猪保持可检测的HAI抗体水平至少245天。这些结果表明，这些DNA疫苗能够在猪中诱导病毒特异性记忆B细胞和持久的免疫应答，其水平高于用商业福尔马林灭活的乙脑疫苗获得的水平。(C)北京大学出版社.
Swine are an important amplifier of Japanese encephalitis (JE) virus in the paradomestic environment. In this study, two JE DNA vaccine candidates were evaluated for immunogenicity, in swine. Both vaccine plasmids encode a cassette consisting of the signal of premembrane (prM), prM, and envelope (E) coding regions of JE virus. One plasmid, designated pcJEME, is based on a commercial vector (pcDNA3), whereas the other plasmid, designated pNJEME, is based on a vector (pNGVL4a) designed to address some of the safety concerns of DNA vaccine use. No differences were detected in the immunogenicity of these two plasmids in mice or swine. Swine immunized with the DNA vaccines at a dose of 100 to 450 mu g at an interval of 3 weeks developed neutralizing and hemagglutination-inhibitory (HAI) antibody titers of 1:40 to 1:160 at 1 week after the second immunization. However, swine administered two doses of a commercial JE vaccine (formalin-inactivated virus preparation; JEVAX-A) developed low (1:10) or undetectable antibody responses after their boost. Interestingly, serum antibody titers elicited by DNA vaccines in swine were higher than those detected in mice. Eight days after boosting with viral antigen (JEVAX-A) to detect an anamnestic response, swine immunized two times with the DNA vaccine showed a >100-fold elevation in HAI titer, indicating a strong recall of antibody response. Swine maintained detectable levels of HAI antibody for at least 245 days after two immunizations with a UNA vaccine. These results indicate that these DNA vaccines are able to induce virus-specific memory B cells and long-lasting antibiodies in swine, which were of higher levels than those obtained with a commercial formalin-inactivated JE vaccine. (C) 2000 Academic Press.