Recent Advances in Zika Virus Vaccine Development

Abstract

Figure 1: Three different mechanisms of ADE (Antibody-dependent enhancement):A-receptors on virus particles bound by cross-reactive antibody get conformational change in structure that results in high affinity with the corresponding receptor on the host cell membrane. The corresponding receptor was not able to recognize the viral receptor before this conformational change. B-The cross-reactive antibody binds to viral and host cell membrane receptors at the same time bringing the viral particle near to the host cell. C-The Fc component of the cross-reactive antibody is recognized by the corresponding receptor on host cell membrane being the predominant mechanism of ADE phenomenon. [DENV], are the primary focus for the current vaccine and therapeutic research against ZV. Zika virus spreads by a mosquito, Anopheles Aegypti. [16] In addition to the mosquito bite, the vertical transmission, from mother to baby during pregnancy, and the sexual transmission have also been reported. Transmission[25] ZV infection is characterized by mild rash and fever.[22] However, where it infects the cells of nervous system may result in severe non-reversible complications. The neurological complications include Guillain-Barre (GB) syndrome characterized by neuromuscular paralysis .[24] ZV infection during pregnancy causes Congenital Zika Virus syndrome (CZS) which is a defined set of congenital conditions in newborns. CZS consists of microcephaly, decreased brain tissue, damage to the back of the eye, joints with limited movement and increased muscle tone . [7] Microcephaly, where the head circumference of newborn is less than thirty-two cms, has been the hallmark of the teratogenicity of ZV maternal infection.[2] ZV infection in pregnancy complicated with the microcephalic baby is a major cause of the anxiety and depression among the reproductive age women of ZV endemic area.[10] In adult men, ZV keeps on shedding in semen for more than two months after infection and damages spermatogonia in male reproductive organs resulting in male infertility.[19] Therefore, the consequences of ZV epidemic are affecting next human generations.The phenomenon of Antibody Dependent Enhancement of infection (ADE) is an important risk for the sample selection in clinical trials for monoclonal antibodies. Antibody Dependent Enhancement of infection is the phenomenon that results in magnifying the host cell infection by the viruses of same family due to the presence of cross-reactive antibodies. The respective antibodies recognize the receptors on the viral particle and the host cell membrane. These antibodies may be produced against one type of virus, for example Dengue Virus and can cross-react with the same epitopes present on the Zika Virus (ZV). There are three proposed mechanisms of ' ADE, the first one being recognition of the receptor on the surface of virus particle, inducing a conformational change in the structure of the receptor that increases its affinity for a corresponding receptor on the host cell membrane (Figure 1 A). In the second me...