A Plasmodium vivax Plasmid DNA- and Adenovirus-Vectored Malaria Vaccine Encoding Blood-Stage Antigens AMA1 and MSP142 in a Prime/Boost Heterologous Immunization Regimen Partially Protects Aotus Monkeys against Blood-Stage Challenge

Q2 Biochemistry, Genetics and Molecular Biology

Clinical and Vaccine Immunology Pub Date : 2017-02-08 DOI:10.1128/CVI.00539-16

N. Obaldía, M. Stockelman, W. Otero, J. Cockrill, Harini Ganeshan, E. Abot, Jianfeng Zhang, K. Limbach, Y. Charoenvit, D. Doolan, D. Tang, T. Richie

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引用次数: 13

Abstract

ABSTRACT Malaria is caused by parasites of the genus Plasmodium, which are transmitted to humans by the bites of Anopheles mosquitoes. After the elimination of Plasmodium falciparum, it is predicted that Plasmodium vivax will remain an important cause of morbidity and mortality outside Africa, stressing the importance of developing a vaccine against P. vivax malaria. In this study, we assessed the immunogenicity and protective efficacy of two P. vivax antigens, apical membrane antigen 1 (AMA1) and the 42-kDa C-terminal fragment of merozoite surface protein 1 (MSP142) in a plasmid recombinant DNA prime/adenoviral (Ad) vector boost regimen in Aotus monkeys. Groups of 4 to 5 monkeys were immunized with plasmid DNA alone, Ad alone, prime/boost regimens with each antigen, prime/boost regimens with both antigens, and empty vector controls and then subjected to blood-stage challenge. The heterologous immunization regimen with the antigen pair was more protective than either antigen alone or both antigens delivered with a single vaccine platform, on the basis of their ability to induce the longest prepatent period and the longest time to the peak level of parasitemia, the lowest peak and mean levels of parasitemia, the smallest area under the parasitemia curve, and the highest self-cure rate. Overall, prechallenge MSP142 antibody titers strongly correlated with a decreased parasite burden. Nevertheless, a significant proportion of immunized animals developed anemia. In conclusion, the P. vivax plasmid DNA/Ad serotype 5 vaccine encoding blood-stage parasite antigens AMA1 and MSP142 in a heterologous prime/boost immunization regimen provided significant protection against blood-stage challenge in Aotus monkeys, indicating the suitability of these antigens and this regimen for further development.

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编码血期抗原AMA1和MSP142的间日疟原虫质粒DNA和腺病毒载体疟疾疫苗在初始/增强异种免疫方案中部分保护猕猴免受血期攻击

疟疾是一种由疟原虫属寄生虫引起的疾病，通过按蚊叮咬传播给人类。在消灭恶性疟原虫之后，预计间日疟原虫仍将是非洲以外地区发病和死亡的一个重要原因，这强调了开发间日疟原虫疟疾疫苗的重要性。本研究在重组DNA引物/腺病毒(Ad)载体增强方案中，评估了两种间日疟原虫抗原——顶膜抗原1 (AMA1)和merozoite表面蛋白1 (MSP142) 42-kDa c端片段的免疫原性和保护效果。每组4 - 5只猴子分别接种质粒DNA、Ad、每种抗原的启动/增强方案、两种抗原的启动/增强方案和空载体对照，然后进行血期免疫。抗原对异种免疫方案的保护作用优于单一疫苗平台单独递送抗原或同时递送抗原的免疫方案，其诱导的潜伏期最长，达到寄生虫病高峰的时间最长，寄生虫病高峰和平均水平最低，寄生虫病曲线下面积最小，自治率最高。总体而言，攻毒前MSP142抗体滴度与寄生虫负荷下降密切相关。然而，很大比例的免疫动物出现了贫血。由此可见，编码血期寄生虫抗原AMA1和MSP142的间日疟原虫质粒DNA/Ad血清5型疫苗在异源初始/增强免疫方案中对猕猴的血期攻击具有显著的保护作用，表明这些抗原和该方案具有进一步开发的适应性。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Clinical and Vaccine Immunology 医学-传染病学

CiteScore

2.88

自引率

0.00%

发文量

审稿时长

1.5 months

期刊介绍： Cessation. First launched as Clinical and Diagnostic Laboratory Immunology (CDLI) in 1994, CVI published articles that enhanced the understanding of the immune response in health and disease and after vaccination by showcasing discoveries in clinical, laboratory, and vaccine immunology. CVI was committed to advancing all aspects of vaccine research and immunization, including discovery of new vaccine antigens and vaccine design, development and evaluation of vaccines in animal models and in humans, characterization of immune responses and mechanisms of vaccine action, controlled challenge studies to assess vaccine efficacy, study of vaccine vectors, adjuvants, and immunomodulators, immune correlates of protection, and clinical trials.