Challenges in Dengue Vaccines Development: Pre-existing Infections and Cross-Reactivity

被引:41
作者
Izmirly, Abdullah M. [1 ,2 ,3 ]
Alturki, Sana O. [2 ,3 ]
Alturki, Sawsan O. [2 ,3 ]
Connors, Jennifer [1 ,2 ]
Haddad, Elias K. [1 ,2 ]
机构
[1] Drexel Univ, Coll Med, Dept Med, Div Infect Dis & HIV Med, Philadelphia, PA 19104 USA
[2] Drexel Univ, Coll Med, Dept Microbiol & Immunol, Philadelphia, PA 19104 USA
[3] King Abdulaziz Univ, Fac Appl Med Sci, Dept Med Technol, Jeddah, Saudi Arabia
来源
FRONTIERS IN IMMUNOLOGY | 2020年 / 11卷
关键词
dengue (DENV); adenosine deaminase (ADA); antibody dependent enhancement (ADE); challenges of vaccine development; T follicular helper cells (Tfh); cross-reactivity; ANTIBODY-DEPENDENT ENHANCEMENT; MEMORY TFH CELLS; HELPER T-CELLS; TETRAVALENT VACCINE; IMMUNE-RESPONSES; DENDRITIC CELLS; VIRUS-INFECTION; LATIN-AMERICA; PHASE-II; IMMUNOGENICITY;
D O I
10.3389/fimmu.2020.01055
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
Dengue is one of the most frequently transmitted mosquito-borne diseases in the world, which creates a significant public health concern globally, especially in tropical and subtropical countries. It is estimated that more than 390 million people are infected with dengue virus each year and around 96 million develop clinical pathologies. Dengue infections are not only a health problem but also a substantial economic burden. To date, there are no effective antiviral therapies and there is only one licensed dengue vaccine that only demonstrated protection in the seropositive (Immune), naturally infected with dengue, but not dengue seronegative (Naive) vaccines. In this review, we address several immune components and their interplay with the dengue virus. Additionally, we summarize the literature pertaining to current dengue vaccine development and advances. Moreover, we review some of the factors affecting vaccine responses, such as the pre-vaccination environment, and provide an overview of the significant challenges that face the development of an efficient/protective dengue vaccine including the presence of multiple serotypes, antibody-dependent enhancement (ADE), as well as cross-reactivity with other flaviviruses. Finally, we discuss targeting T follicular helper cells (Tfh), a significant cell population that is essential for the production of high-affinity antibodies, which might be one of the elements needed to be specifically targeted to enhance vaccine precision to dengue regardless of dengue serostatus.
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页数:15
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