Measles as a Vector for the Malaria Vaccine Development

N. Penta, Gaurav K Gupta, R. Glueck
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Abstract

Classical viral vectors have been successfully used to deliver Malaria, HPV antigens. Emerging viral vector technologies such as Measles virus (MV) are useful for vaccine development. Studies in animal models suggest that each viral vector is unique in its ability to induce humoral and cellular responses. Measles virus is a member of Mononegavirales thus the genomic RNA is not translated either in vivo or in vitro. MV replicates exclusively in the cytoplasm, ruling out the possibility of integration into host DNA. Live attenuated Measles (MeV) are thus inducing long lived immunity after a single immunization dose. MeV vector allows insertion and stable expression over multiple replications round of various genes from different genome positions, allowing comparable immunity against MeV proteins and vectored antigens. Hence in the present study we identified the novel target for Malaria vaccine development, N-terminal region of Merozite surface protein 1 (MSP-1). The present invention relates to a combined Measles Malaria vaccine containing different attenuated recombinant measles malaria vectors comprising a heterologus nucleic acid encoding several Plasmodium falciparum antigens. Preferably it relates to a viral vector that comprise nucleic acids encoding the circumsporozoite (CS) protein of P. falciparum, the merozoite surface protein 1 (MSP-1) of P. falciparum and its derivatives (P-42) in its glycosylated and secreted forms.
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麻疹作为疟疾疫苗开发的载体
经典的病毒载体已经成功地用于传递疟疾、HPV抗原。新兴的病毒载体技术,如麻疹病毒(MV),对疫苗开发很有用。动物模型研究表明,每种病毒载体诱导体液和细胞反应的能力都是独一无二的。麻疹病毒是单株病毒的一员,因此其基因组RNA在体内或体外都不会被翻译。MV只在细胞质中复制,排除了与宿主DNA整合的可能性。因此,减毒活麻疹(MeV)在单次免疫剂量后可诱导长期免疫。MeV载体允许插入和稳定表达来自不同基因组位置的各种基因的多次复制,允许对MeV蛋白和载体抗原的可比免疫。因此,在本研究中,我们确定了疟疾疫苗开发的新靶点,Merozite表面蛋白1 (MSP-1)的n端区域。本发明涉及一种麻疹疟疾联合疫苗,该疫苗含有含有编码几种恶性疟原虫抗原的异源核酸的不同减毒重组麻疹疟疾载体。优选地,它涉及一种病毒载体,其包含编码恶性疟原虫环孢子子(CS)蛋白、恶性疟原虫merozoite表面蛋白1 (MSP-1)及其糖基化和分泌形式的衍生物(P-42)的核酸。
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