A single dose recombinant AAV based CHIKV vaccine elicits robust and durable protective antibody responses in mice.

IF 3.4 2区医学 Q1 PARASITOLOGY

PLoS Neglected Tropical Diseases Pub Date : 2024-11-04 DOI:10.1371/journal.pntd.0012604

Qin-Xuan Zhu, Ya-Nan Zhang, Hong-Qing Zhang, Chao Leng, Cheng-Lin Deng, Xin Wang, Jia-Jia Li, Xiang-Li Ye, Bo Zhang, Xiao-Dan Li

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Abstract

Background: Chikungunya virus (CHIKV) is a mosquito-borne alphavirus that is responsible for Chikungunya fever, which is characterized by fever, rash, and debilitating polyarthralgia. Since its re-emergence in 2004, CHIKV has continued to spread to new regions and become a severe health threat to global public. Development of safe and single dose vaccines that provide durable protection is desirable to control the spread of virus. The recombinant adeno-associated virus (rAAV) vectors represent promising vaccine platform to provide prolonged protection with a single-dose immunization. In this study, we developed a rAAV capsid serotype 1 vector based CHIKV vaccine and evaluated its protection effect against CHIKV challenge.

Methodology: The recombinant AAV1 encoding the full-length structural proteins of CHIKV (named as rAAV1-CHIKV-SP) was generated in vitro by transfecting the plasmids of AAV helper-free system into HEK-293T cells. The safety and immunogenicity of rAAV1-CHIKV-SP were tested in 4-week-old C57BL/6 mice. The antibody responses of the mice receiving prime-boost or single-dose immunization of the vaccine were determined by ELISA and plaque reduction neutralizing test. The immunized mice were challenged with CHIKV to evaluate the protection effect of the vaccine.

Conclusions: The rAAV1-CHIKV-SP showed remarkable safety and immunogenicity in C57BL/6 mice. A single dose intramuscular injection of rAAV1-CHIKV-SP elicited high level and long-lasting antibody responses, and conferred complete protection against a heterologous CHIKV strain challenge. These results suggest rAAV1-CHIKV-SP represents a promising vaccine candidate against different CHIKV clades with a simplified immunization strategy.

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以重组 AAV 为基础的单剂量 CHIKV 疫苗可在小鼠体内激发强效持久的保护性抗体反应。

背景：基孔肯雅病毒（CHIKV）是一种由蚊子传播的α-病毒，是导致基孔肯雅热的罪魁祸首，基孔肯雅热的特征是发热、皮疹和令人衰弱的多关节痛。自 2004 年再次出现以来，CHIKV 不断向新的地区传播，对全球公众的健康构成严重威胁。为控制病毒传播，我们需要开发安全且能提供持久保护的单剂量疫苗。重组腺相关病毒（rAAV）载体是一种很有前景的疫苗平台，可通过单剂免疫提供长期保护。在这项研究中，我们开发了一种基于rAAV帽盖血清型1载体的CHIKV疫苗，并评估了其对CHIKV挑战的保护效果：方法：通过将无辅助系统的AAV质粒转染到HEK-293T细胞中，在体外产生了编码CHIKV全长结构蛋白的重组AAV1（命名为rAAV1-CHIKV-SP）。在 4 周大的 C57BL/6 小鼠中测试了 rAAV1-CHIKV-SP 的安全性和免疫原性。通过酶联免疫吸附试验（ELISA）和斑块还原中和试验确定了小鼠对疫苗原代加强免疫或单剂免疫的抗体反应。对免疫小鼠进行CHIKV挑战，以评估疫苗的保护效果：rAAV1-CHIKV-SP在C57BL/6小鼠中表现出显著的安全性和免疫原性。单剂量肌肉注射 rAAV1-CHIKV-SP 可引起高水平和持久的抗体反应，并对异源 CHIKV 株挑战产生完全保护作用。这些结果表明，rAAV1-CHIKV-SP 是一种很有前途的候选疫苗，可通过简化的免疫策略预防不同的 CHIKV 支系。

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来源期刊

PLoS Neglected Tropical Diseases PARASITOLOGY-TROPICAL MEDICINE

自引率

10.50%

发文量

723

期刊介绍： PLOS Neglected Tropical Diseases publishes research devoted to the pathology, epidemiology, prevention, treatment and control of the neglected tropical diseases (NTDs), as well as relevant public policy. The NTDs are defined as a group of poverty-promoting chronic infectious diseases, which primarily occur in rural areas and poor urban areas of low-income and middle-income countries. Their impact on child health and development, pregnancy, and worker productivity, as well as their stigmatizing features limit economic stability. All aspects of these diseases are considered, including: Pathogenesis Clinical features Pharmacology and treatment Diagnosis Epidemiology Vector biology Vaccinology and prevention Demographic, ecological and social determinants Public health and policy aspects (including cost-effectiveness analyses).